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EvidenceLib · Open-access article · Immunology

Physical interventions to interrupt or reduce the spread of respiratory viruses

Tom Jefferson, Liz Dooley, Eliana Ferroni, Lubna A Al-Ansary, Mieke L Driel, Ghada A Bawazeer, Mark A Jones, Tammy C Hoffmann et al.

The Cochrane Database of Systematic Reviews 2023 · doi:10.1002/14651858.CD006207.pub6

CC BY 4.0Full textApproximately 243 min read391 references

Table of Contents

AbstractSummary of findingsBackgroundObjectivesMethodsResultsDiscussionAuthors' conclusionsWhat's newHistoryNotesReferences

Abstract

Background

Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review last published in 2020. We include results from studies from the current COVID‐19 pandemic.

Objectives

To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses.

Search methods

We searched CENTRAL, PubMed, Embase, CINAHL, and two trials registers in October 2022, with backwards and forwards citation analysis on the new studies.

Selection criteria

We included randomised controlled trials (RCTs) and cluster‐RCTs investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, glasses, and gargling) to prevent respiratory virus transmission.

Data collection and analysis

We used standard Cochrane methodological procedures.

Main results

We included 11 new RCTs and cluster‐RCTs (610,872 participants) in this update, bringing the total number of RCTs to 78. Six of the new trials were conducted during the COVID‐19 pandemic; two from Mexico, and one each from Denmark, Bangladesh, England, and Norway. We identified four ongoing studies, of which one is completed, but unreported, evaluating masks concurrent with the COVID‐19 pandemic. Many studies were conducted during non‐epidemic influenza periods. Several were conducted during the 2009 H1N1 influenza pandemic, and others in epidemic influenza seasons up to 2016. Therefore, many studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID‐19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high‐income countries; crowded inner city settings in low‐income countries; and an immigrant neighbourhood in a high‐income country. Adherence with interventions was low in many studies. The risk of bias for the RCTs and cluster‐RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included 12 trials (10 cluster‐RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and 10 in the community). Wearing masks in the community probably makes little or no difference to the outcome of influenza‐like illness (ILI)/COVID‐19 like illness compared to not wearing masks (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials, 276,917 participants; moderate‐certainty evidence. Wearing masks in the community probably makes little or no difference to the outcome of laboratory‐confirmed influenza/SARS‐CoV‐2 compared to not wearing masks (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate‐certainty evidence). Harms were rarely measured and poorly reported (very low‐certainty evidence). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). We are very uncertain on the effects of N95/P2 respirators compared with medical/surgical masks on the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; 3 trials, 7779 participants; very low‐certainty evidence). N95/P2 respirators compared with medical/surgical masks may be effective for ILI (RR 0.82, 95% CI 0.66 to 1.03; 5 trials, 8407 participants; low‐certainty evidence). Evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirators compared to medical/surgical masks probably makes little or no difference for the objective and more precise outcome of laboratory‐confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; 5 trials, 8407 participants; moderate‐certainty evidence). Restricting pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies (very low‐certainty evidence). One previously reported ongoing RCT has now been published and observed that medical/surgical masks were non‐inferior to N95 respirators in a large study of 1009 healthcare workers in four countries providing direct care to COVID‐19 patients. Hand hygiene compared to control Nineteen trials compared hand hygiene interventions with controls with sufficient data to include in meta‐analyses. Settings included schools, childcare centres and homes. Comparing hand hygiene interventions with controls (i.e. no intervention), there was a 14% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.86, 95% CI 0.81 to 0.90; 9 trials, 52,105 participants; moderate‐certainty evidence), suggesting a probable benefit. In absolute terms this benefit would result in a reduction from 380 events per 1000 people to 327 per 1000 people (95% CI 308 to 342). When considering the more strictly defined outcomes of ILI and laboratory‐confirmed influenza, the estimates of effect for ILI (RR 0.94, 95% CI 0.81 to 1.09; 11 trials, 34,503 participants; low‐certainty evidence), and laboratory‐confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials, 8332 participants; low‐certainty evidence), suggest the intervention made little or no difference. We pooled 19 trials (71, 210 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. Pooled data showed that hand hygiene may be beneficial with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.83 to 0.94; low‐certainty evidence), but with high heterogeneity. In absolute terms this benefit would result in a reduction from 200 events per 1000 people to 178 per 1000 people (95% CI 166 to 188). Few trials measured and reported harms (very low‐certainty evidence). We found no RCTs on gowns and gloves, face shields, or screening at entry ports.

Authors' conclusions

The high risk of bias in the trials, variation in outcome measurement, and relatively low adherence with the interventions during the studies hampers drawing firm conclusions. There were additional RCTs during the pandemic related to physical interventions but a relative paucity given the importance of the question of masking and its relative effectiveness and the concomitant measures of mask adherence which would be highly relevant to the measurement of effectiveness, especially in the elderly and in young children. There is uncertainty about the effects of face masks. The low to moderate certainty of evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory‐confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under‐investigated. There is a need for large, well‐designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs.

Summary of findings

Summary of findings 1 Medical/surgical masks compared to no masks for preventing the spread of viral respiratory illness
Randomised studies: medical/surgical masks compared to no masks for preventing the spread of viral respiratory illness
Patient or population: general population
Setting: community and hospitals
Intervention: medical/surgical masks
Comparison: no masks
OutcomesAnticipated absolute effects* (95% CI)Relative effect
(95% CI)№ of participants
(studies)Certainty of the evidence
(GRADE)Comments
Risk with no masksRisk with randomised studies: masks
Viral respiratory illness ‐ influenza/COVID‐like illnessStudy populationRR 0.95
(0.84 to 1.09)276,917
(9 RCTs)⊕⊕⊕⊝
Moderatea 
160 per 1000152 per 1000
(134 to 174)
Viral respiratory illness ‐ laboratory‐confirmed influenza/SARS‐CoV‐2Study populationRR 1.01
(0.72 to 1.42)13,919 (6 RCTs)⊕⊕⊕⊝
Moderateb 
40 per 100040 per 1000
(29 to 57)
Adverse events‐‐(3 RCTs)⊕⊝⊝⊝
Very lowa,cAdverse events were not reported consistently and could not be meta‐analysed.Adverse events reported for masks included warmth, discomfort, respiratory difficulties, humidity, pain, and shortness of breath, in up to 45% of participants.
*The risk in the intervention group (and its 95% confidence interval) is based on the median observed risk in the comparison group of included studies and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
Summary of findings 2 N95 respirators compared to medical/surgical masks for preventing the spread of viral respiratory illness
Randomised studies: N95 respirators compared to medical/surgical masks for preventing the spread of viral respiratory illness
Patient or population: general population and healthcare workers
Setting: hospitals and households
Intervention: N95 masks
Comparison: medical/surgical masks
OutcomesAnticipated absolute effects* (95% CI)Relative effect
(95% CI)№ of participants
(studies)Certainty of the evidence
(GRADE)Comments
Risk with medical masksRisk with randomised studies: N95
Viral respiratory illness ‐ clinical respiratory illnessStudy populationRR 0.70
(0.45 to 1.10)7799 (3 RCTs)⊕⊝⊝⊝
Very Lowa,b,cAll studies were conducted in hospital settings with healthcare workers.
120 per 100084 per 1000
(54 to 132)
Viral respiratory illness ‐ influenza‐like illnessStudy populationRR 0.82
(0.66 to 1.03)8407 (5 RCTs)⊕⊕⊝⊝
Lowa,b1 study was conducted in households (MacIntyre 2009).
50 per 100041 per 1000
(33 to 52)
Viral respiratory illness ‐ laboratory‐confirmed influenzaStudy populationRR 1.10
(0.90 to 1.34)8407 (5 RCTs)⊕⊕⊕⊝
Moderateb1 study was conducted in households (MacIntyre 2009).
70 per 100077 per 1000
(63 to 94)
Adverse events‐   ‐(5 RCTs)⊕⊝⊝⊝ 
Very Lowa,b,c
 There was insufficient consistent reporting of adverse events to enable meta‐analysis.Only 1 study reported detailed adverse events: discomfort was reported in 41.9% of N95 wearers versus 9.8% of medical mask wearers (P < 0.001); headaches were more common with N95 (13.4% versus 3.9%; P < 0.001); difficulty breathing was reported more often in the N95 group (19.4% versus 12.5%; P = 0.01); and N95 caused more problems with pressure on the nose (52.2% versus 11.0%; P < 0.001). 4 RCTs either reported no adverse events or only reported on comfort wearing masks.
*The risk in the intervention group (and its 95% confidence interval) is based on the median risk in the comparison group and the observed relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
Summary of findings 3 Hand hygiene compared to control for preventing the spread of viral respiratory illness
Hand hygiene compared to control for preventing the spread of viral respiratory illness
Patient or population: general population and healthcare workers
Setting: schools, childcare centres, homes, offices, nursing homes
Intervention: hand hygiene
Comparison: control
OutcomesAnticipated absolute effects* (95% CI)Relative effect
(95% CI)№ of participants
(studies)Certainty of the evidence
(GRADE)Comments
Risk with controlRisk with hand hygiene
Acute respiratory illnessStudy populationRR 0.86
(0.81 to 0.90)52,105 (9 RCTs)⊕⊕⊕⊝
Moderatea 
380 per 1000327 per 1000
(308 to 342)
Influenza‐like illnessStudy populationRR 0.94
(0.81 to 1.09)34,503 (11 RCTs)⊕⊕⊝⊝
Lowa,b 
90 per 100085 per 1000
(73 to 98)
Laboratory‐confirmed influenzaStudy populationRR 0.91
(0.63 to 1.30)8332 (8 RCTs)⊕⊕⊝⊝
Lowb,c 
80 per 100073 per 1000
(50 to 104)
Composite of acute respiratory illness, influenza‐like illness, laboratory‐confirmed influenzaStudy populationRR 0.89(0.83 to 0.94)71,210 (19 RCTs)⊕⊕⊝⊝
Lowa,b 
200 per 1000178 per 1000(166 to 188)
Adverse events‐‐(2 RCTs)⊕⊝⊝⊝ Very lowa,b,cData were insufficient to conduct meta‐analysis.1 study reported that no adverse events were observed, and another study reported that skin reaction was recorded for 10.4% of participants in the hand sanitiser group versus 10.3% in the control group.
*The risk in the intervention group (and its 95% confidence interval) is based on the median observed risk in the comparison groups of included studies and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Background

Description of the condition

Epidemic and pandemic viral infections pose a serious threat to people worldwide. Epidemics of note include severe acute respiratory syndrome (SARS) in 2003 and the Middle East respiratory syndrome (MERS), which began in 2012, and the current SARS‐CoV‐2 pandemic. Major pandemics include the H1N1 influenza caused by the H1N1pdm09 virus in 2009 and the coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2.

Even non‐epidemic acute respiratory infections (ARIs) place a huge burden on healthcare systems around the world, and are a prominent cause of morbidity (WHO 2017). Furthermore, ARIs are often antecedents to lower respiratory tract infections (RTIs) caused by bacterial pathogens (i.e. pneumonia), which cause millions of deaths worldwide, mostly in low‐income countries (Schwartz 2018).

High viral load, high levels of transmissibility, susceptible populations, and symptomatic patients are considered to be the drivers of such epidemics and pandemics (Jefferson 2006a). Preventing the spread of respiratory viruses from person to person may be effective at reducing the spread of outbreaks.

Physical interventions, such as the use of masks and physical distancing measures, might prevent the spread of respiratory viruses which are considered to be transmitted by multiple modes of transmission including by respiratory particles of varying sizes spreading from infected to susceptible people and through direct and indirect contact (Kutter 2018; Leung 2021). It is recognised that there is a continuum of respiratory particle sizes varying between large droplet to fine aerosols, which is an important concept. Particles of a variety of sizes may be expelled from the human airway during coughing, sneezing, singing, talking, and during certain medical procedures (WHO 2021). In addition, transmission of respiratory viruses is likely highly complex, dependent on multiple host, virus and environmental factors, plus the myriad of interactions between these factors, which may influence the predominant modes of transmission in any given setting (Broderick 2008; Hendley 1988; Kutter 2018; Leung 2021). Current evidence suggests that the virus responsible for the current COVID‐19 pandemic spreads mainly between people who are in close contact with each other (Onakpoya 2022a).

It is also unknown if all respiratory viruses or different strains of a specific respiratory virus transmit in a similar manner, further adding to the complexity of respiratory virus transmission.

Description of the intervention

Single measures of intervention such as the use of vaccines or antivirals, may be insufficient to contain the spread of influenza, but combinations of interventions may reduce the reproduction number to below 1 (Demicheli 2018a; Demicheli 2018b; Jefferson 2014; Jefferson 2018; Thomas 2010). When the reproduction number (or R0) is below 1, each infection causes less than one new secondary infection and the disease will eventually die out. For some respiratory viruses there are no licensed interventions, and a combination of social and physical interventions may be the only option to reduce the spread of outbreaks, particularly those that may be capable of becoming epidemic or pandemic in nature (Luby 2005). Such interventions were emphasised in the World Health Organization's latest Global Influenza Strategy 2019 to 2030, and have several possible advantages over other methods of suppressing ARI outbreaks since they may be instituted rapidly and may be independent of any specific type of infective agent, including novel viruses. In addition, the possible effectiveness of public health measures during the Spanish flu pandemic of 1918 to 1919 in US cities supports the impetus to investigate the existing evidence on the effectiveness of such interventions (Bootsma 2007), including quarantine (such as isolation, physical distancing) and the use of disinfectants. We also considered the major societal implications for any community adopting these measures (CDC 2005a; CDC 2005b; WHO 2006b; WHO 2020a; WHO 2020b).

How the intervention might work

Epidemics and pandemics are more likely during antigenic change (changes in the viral composition) in the virus or transmission from animals (domestic or wild) when there is no natural human immunity (Bonn 1997). High viral load, high levels of transmissibility, and symptomatic patients are considered to be the drivers of such epidemics and pandemics (Jefferson 2006b).

Physical interventions, such as the use of masks (Greenhalgh 2020; Howard 2020), physical distancing measures, school closures, and limitations of mass gatherings, might prevent the spread of the virus transmitted by infectious respiratory particles from infected to susceptible individuals. The use of hand hygiene, gloves, and protective gowns can also prevent the spread by limiting the transfer of viral particles onto and from fomites (inanimate objects such as flat surfaces, tabletops, utensils, porous surfaces, or nowadays cell phones, which can transmit the agent if contaminated) (Onakpoya 2022b). Such public health measures were widely adopted during the Spanish flu pandemic and have been the source of considerable debate (Bootsma 2007).

Why it is important to do this review

Although the benefits of physical interventions seem self‐evident, given the global importance of interrupting respiratory virus transmission, having up‐to‐date estimates of their effectiveness is necessary to inform planning, decision‐making, and policy. The continuance of outbreaks of COVID‐19 and the reporting of several new trials assessing different barrier interventions in preventing the spread of SARS‐COV‐2 virus, have prompted this update (WHO 2022). Physical methods have several possible advantages over other methods of suppressing ARI outbreaks, including their rapid deployment and ability to be independent of the infective agent, including novel viruses.

The hallmark of the 2020 update was shifting from including all types of studies to a focus on randomised controlled trials (RCTs) only, which had substantially increased in number. This change enabled more robust evidence summaries from high‐quality studies, which are much less prone to the risk of the multiple biases associated with observational studies, to help policy and decision makers in making national and global recommendations. The 2020 update identified 67 relevant studies, but none were carried out during the COVID‐19 pandemic (Jefferson 2020). The three key messages of that update were: (1) hand hygiene programmes may help to slow the spread of respiratory viruses; (2) uncertainty whether wearing masks or N95/P2 respirators would help in slowing the spread of respiratory viruses; and (3) few studies were identified for other interventions. One study looked at quarantine, and none looked at eye protection, gowns and gloves, or screening people when they entered a country. However, during the last search of the 2020 update, six ongoing, unpublished studies were identified; three of them evaluate masks in COVID‐19. The review authors are aware that several trials have now been published since the publication of the 2020 update, warranting this new update.

This is the fifth update (Jefferson 2009; Jefferson 2010; Jefferson 2011; Jefferson 2020) of a Cochrane Review first published in 2007 (Jefferson 2007).

Objectives

To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses.

Methods

Criteria for considering studies for this review

Types of studies

For this 2022 update we only considered individual‐level randomised controlled trials (RCTs), or cluster‐RCTs, or quasi‐RCTs for inclusion.

In versions of this review prior to 2020 we also included observational studies (cohorts, case‐controls, before‐after, and time series studies). However, for this update there were sufficient randomised studies to address our study aims, so we excluded observational studies because randomisation is the optimal method to prevent systematic differences between participants in different intervention groups and, further, deciding who receives an intervention and who does not is influenced by many factors, including prognostic factors (Higgins 2011). This point is particularly relevant here because individuals who chose to implement physical interventions are likely to use multiple interventions, thus making it difficult to separate out the effect of single interventions. Further, they are likely to be different from individuals who do not implement physical interventions in ways that are difficult to measure.

Types of participants

People of all ages.

Types of interventions

We included RCTs and cluster‐RCTs of trials investigating physical interventions or combinations of interventions to prevent respiratory virus transmission compared with doing nothing or with other interventions. The interventions of interest included: screening at entry ports, isolation, quarantine, physical distancing, personal protection (clothing, gloves, devices), hand hygiene, face masks, gargling, nasal washes, eye protective devices, face shields, disinfecting, and school closure.

Types of outcome measures

For the outcomes listed below we had no predetermined key time points of interest or adverse events of special interest, however, methods of assessment of cases of viral respiratory illness based on laboratory‐confirmation needed to be based on an accurate test in combination with critical additional information. For example, a polymerase chain reaction (PCR) test in combination with symptoms of disease, or a serological test at baseline as well as at the end of follow‐up were acceptable methods. Further, we stratified analyses by study‐specific definitions for cases of viral respiratory illness which included a broad definition of acute respiratory infection (ARI), a more specific definition of influenza‐like‐illness (ILI), and the most precise definition of a laboratory‐confirmed respiratory infection that identified the actual viral pathogen. For the studies conducted during the COVID‐19 pandemic, we assumed that COVID‐like illness was interchangeable with ILI. In the case of laboratory‐confirmed respiratory infection we separated out SARS‐CoV‐2/influenza and other viral pathogens. We did not pool these outcomes as it cannot be assumed that the effects of physical interventions will be the same for the different viral pathogens. The one exception was for the comparison of hand‐hygiene versus control where the estimated effects for ARI, ILI and laboratory‐confirmed infection were highly consistent.

Primary outcomes

Numbers of cases of viral respiratory illness (including acute respiratory infections (ARI), influenza‐like illness (ILI), COVID‐like illness and laboratory‐confirmed influenza, SARS‐CoV‐2 or other viral pathogens).Adverse events related to the intervention.

Secondary outcomes

Deaths.Severity of viral respiratory illness as reported in the studies.Absenteeism.Hospital admissions.Complications related to the illness, e.g. pneumonia.

Search methods for identification of studies

Electronic searches

For this 2022 update, we refined the original search strategy using a combination of previously included studies and automation tools (Clark 2020). We converted this search using the Polyglot Search Translator (Clark 2020), and ran the searches in the following databases:

the Cochrane Central Register of Controlled Trials (CENTRAL) (2022, Issue 09), which includes the Acute Respiratory Infections Group's Specialised Register (searched 04 October 2022) (Appendix 1);PubMed (01 January 2020 to 04 October 2022) (Appendix 2);Embase (01 January 2020 to 04 October 2022) (Appendix 3);CINAHL (Cumulative Index to Nursing and Allied Health Literature) (01 January 2020 to 04 October) (Appendix 4);US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (January 2010 to 04 October 2022); andWorld Health Organization International Clinical Trials Registry Platform (January 2010 to 04 October 2022).

We combined the database searches with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity‐ and precision‐maximising version (2008 revision) (Lefebvre 2011). Details of previous searches are available in Appendix 5.

Searching other resources

We conducted a backwards‐and‐forwards citation analysis in Scopus on all newly included studies to identify other potentially relevant studies.

Data collection and analysis

Selection of studies

The search and citation analysis results were initially screened via the RobotSearch tool (Marshall 2018) to exclude all studies that were obviously not RCTs. We scanned the titles and abstracts of studies identified by the searches. We obtained the full‐text articles of studies that either appeared to meet our eligibility criteria or for which there was insufficient information to exclude it. We then used a standardised form to assess the eligibility of each study based on the full article.

Data extraction and management

Five review authors (LA/GB/EF/EB/TOJ) independently applied the inclusion criteria to all identified and retrieved articles, and extracted data using a standard template that had been developed for and applied to previous versions of the review, but was revised to reflect our focus on RCTs and cluster‐RCTs for this update. We resolved any disagreements through discussion with either PG or JMC acting as arbiter. We extracted and reported descriptions of interventions using the Template for Intervention Description and Replication (TIDieR) template (Table 4).

1 Description of interventions in included studies, using the items from the Template for Intervention Description and Replication (TIDieR) checklist
Author, yearBrief nameRecipientWhyWhat (materials)What (procedures)Who providedHowWhereWhen and how muchTailoringModification of intervention throughout trialStrategies to improve or maintain intervention fidelityExtent of intervention fidelity
Masks compared to either no masks or different mask types
Abaluck 2022(additional sources: Abaluck 2021a, Abaluck 2021b, Kwong 2021)Community‐level mask promotion and distribution of free masks.A. Cloth masks orB. Surgical masks with possible additional village level elements: i) incentiveii) signageiii) text message reminderand household elements:i) altruism or self‐protection messagesii) amount of households receiving textsiii) commitment to mask‐wearingLeaders and adult householders of rural and peri‐urban villagesIncrease large‐scale adoption and proper wearing of face masks to slow the spread of COVID‐19 and save lives informed by research in public health, psychology, economics, marketing, and other social sciences on product promotion and dissemination strategiesMasks colour‐coded by households, either:A. cloth masks: an exterior layer of 100% non‐woven polypropylene (70 grams/m2 [gsm]), 2 interior layers of 60% cotton/40% polyester interlocking knit (190 gsm), an elastic loop that goes around the head above and below the ears, and a nose bridge; filtration efficiency: 37%[1] B. 3 layers of 100% non woven polypropylene[2], elastic ear loops, and a nose bridge; filtration efficiency: 95%.Sticker that had a logo of a mask with an outline of the Bangladeshi flag and a phrase in Bengali that noted the mask could be washed and reused[3]; filtration efficiency of 76% Initial 3 masks per household Video of notable public figures[4] discussing why, how, and when to wear a mask Brochure based on WHO materials depicting proper mask‐wearing Scripted speeches for use by role models and local leaders at Friday prayers Scripted text messages Monetary rewards (USD 190) or non‐monetary reward (certificate) for villages Signage for household doors declaring they are a mask‐wearing household Smart phone for delivery and receipt of text message reminders Loudspeaker for announcements in markets by research staff Masks woven by and procured from local Bangladeshi garment factories within 6 weeks after ordering:$0.50 per cloth mask and $0.13 per surgical mask Masks and hand sanitiser for staff delivering interventionCosts:Cloth masks: $275.10/villageSurgical masks:$88.90/villagePPE for staff: $70/villageMedia costs:$100/villageTransport and other costs: $30/village Handouts and written and some audio scripts for role models, leaders, surveillance officers and texts etc provided by the research team and in online protocol supplement via osf.io/23mws/All villages:1. household distribution of surgical or cloth masks and showing of mask‐wearing video;2. distribution and promotion of masks at village markets;3. mask distribution at mosques;4. mask promotion in public spaces;5. role modelling and advocacy by local leaders, including Imams during Friday prayers using a scripted speech. Periodic monitoring of passers‐by and reminding people to put on masks Some villages:village police accompanying mask promoters, providing monetary rewards or certificates to villages if mask‐wearing rate improves. Some villages:public signalling of mask‐wearing via signage, text message reminders, messaging emphasizing either altruistic or self‐protection motives for mask‐wearing, and extracting verbal commitments from households. Modelling of safe mask wearing by study staff Detailed procedures outlined in online protocol supplement osf.io/23mws/Local NGO staff and volunteers (Bangladeshi NGO GreenVoice)[5] andInnovations for Poverty Action (IPA) Village Imams and police officers No “specialized skills” needed as intervention designed to be easily adopted by other NGOs or agencies Training of staff provided by researchers for mask promotionMasks and promotion delivered face to face in households, markets, mosques and streets of villages both as groups and individually Text messages delivered by phone and individuallyHouseholds, markets, mosques and streets of 572 villages (in rural Bangladesh)8 weeks per village rolled out over a 6 week period (November 2020 to January 2021) 1 day of training per village Once off mask distribution and promotion at households (4 days / village) Mask distribution 3 to 6 days / week at markets and on 3 Fridays at mosques during the first 4 weeks Weekly or biweekly mask promotion Role‐modelling and leader advocacy at Friday prayers Periodic monitoring: 1/week on weeks 1, 2, 4, 6, 8, and 10;daily schedule provided in Protocol – 1 hour per site for 9 sites 8am to 5pm Each village observed on 2 alternating days of the week.Observations occurred 7 days of the week (9 am to 7 pm) Detailed schedules provided in online protocol supplement viaosf.io/23mws/Periodic monitoring and then additional training of staff provided as needed Different locations and timing of observation across different daysIn the first 5 weeks of the study staff found low engagement in some villages with local mask use, so mask promotion staff were retrained by researcher part‐way through the intervention “to work more closely with local leaders and set specific milestones for that partnership” After 5 weeks, monitoring of mask‐wearing was limited to those who appeared to be 18 years or older.Numbers of masks distributed was noted Promoters periodically monitored passers‐by and reminded people to put on masks Direct surveillance of mask wearing, correct mask‐wearing (wearing either a project mask or an alternative face‐covering over the mouth and nose) and physical distancing (if s/he was at least one arm’s length away from the nearest person)[6] Monetary rewards or certificates to villages if mask‐wearing rate improved Additional training for mask promotion staff Recording of activities undertaken by intervention staff including the degree to which leaders or imams understood the script, sites observed etc (see p.9 of Protocol osf.io/23mws/) “consistent with the WHO guideline that defines physical distancing as one meter of separation.” www.who.int/westernpacific/emergencies/covid-19/information/physical-distancing(accessed 13 June 2022).Numbers of masks distributed:A. 370,643B. 924,849 Mask‐wearing:IGs: 42.3%CG: 13.3%Increase was largest in mosques (37% points) and 25% to 29% points in other locations Proper mask‐wearing increased by29.0% Physical distancing increased from 24.1% in CG villages to 29.2% in IG villages No difference between IGs and CGs in number of people observed in public areas, as an indication of social distancing.
Alfelali 2020Face masksHajj pilgrims aged ≥ 18 yearsPrevent and control viral respiratory infections at mass gatherings50 surgical face masks per participant (3M™ Standard Tie‐On surgical mask, Cat No: 1816) Written instructions for mask use (See S1 Appendix)Provide masks and verbal and printed instructions, rules for mask use and demonstration of appropriate mask usage provided (See S1 Appendix) Rules for mask use:• ”Try to avoid touching the front of the mask.• Change your mask if it is damp, wet or dirty.• Always clean your hands before and after changing the masks.• Put used masks in a plastic bag and throw it into a rubbish bin. You will find bins somewhere close to your tent in Mina.”464 volunteer trained research team members approached pilgrims in their tents Training included how to approach pilgrims and explanation and demonstration of mask useIndividually and face to face to groups of pilgrims in tentsTents of pilgrims for Hajj in Makkah (Saudi Arabia) 50 to 150 pilgrims per large tent, sleeping head‐to‐head and sharing meals and ritesMask wearing for 24 hours if possible, over days of Hajj season inside and outside assigned tents 3 consecutive Hajj seasons (5 to 6 days, October 2013 to 2015)Written information provided in preferred language (Arabic or English) Pilgrims who used at least 1 mask each day were considered to have used the mask during that day (i.e. could be < 24 hours)None described4 day diaries of mask use: number of masks used and hours worn each day (see S1 Appendix)Mask use:IG:Daily: 24.7%Intermittently: 47.7%None: 20.9%CG:Daily: 14.3%Intermittently: 34.9%None: 43.7% Mask use of at least 4 hours consistently greater in IG than CG
Barasheed 2014   Supervised mask useReligious pilgrims ≥ 15 yearsPrevent respiratory virus infections at mass gatherings through mask usePlain surgical face masks (3M Standard Tie‐On Surgical Mask, Cat No: 1816) manufactured by 3M company, USA; 5 masks per day
Written instructions on face mask use
Special polythene bags for disposalMasks provided to index case and their contacts with advice on mask use (before prayers, in seminars, and after meals).
Written instructions provided on face mask use, need to change them, and disposal.Not described, presumably the medical researchersFace‐to‐face provision of masks, instructions, and remindersTents of pilgrimage site (Mina Valley, Saudi Arabia)Advice on mask use given throughout pilgrimage stay (5 days)None reported.None reported.The medical researchers followed pilgrims each day to remind participants about recording their mask usage in health diary.Face mask use: mask group: 56/75 (76%), control group: 11/89 (12%)
(P < 0.001)
76% of intervention tents wore masks.
10 of 75 (13%) pilgrims in ‘mask’ tents wore face masks during sleep.
Bundgaard 2021(additional source Bundgaard 2020)Face masks (surgical)Community‐dwelling adults aged 18 years or older with internet accessReduce wearers' risk for SARS‐CoV‐2infection outside the home through protection of the nose and mouth from droplets or aerosols or contaminated fingers and handsPer participant:50 x 3‐layer, disposable, surgical face masks with ear loops(TYPE II EN 14683 (Abena, Denmark); filtration rate, 98%; made in China) 1 badge (saying: “I am testing face masks – for you and me”) Written instructions and instructional videos for proper use of masks (See supplement 8) of published paper including link to video for proper face mask use [in Danish] vimeo.com/406952695Supply of masks sent to home address by courier Provision of written instructions sent by courier about how and when to wear masks including links to instructional video for face mask use Instruction to follow advice of local health authorities (in Denmark) Provision of follow‐up support by email and a phone help‐line for questionsResearchers provided the masks (funded by Salling Group), instructions and follow‐up support Background and training of researcher not described Hotline provided medical expertise and guidance, (qualification and training needed for this support not specified)Individually by mail, email, online and telephoneMask wearing:when outside the home ‐ and in the home when they had guests (in Denmark) Instructions and support at home and onlineMask wearing:whenever outside the home or when guests in the home, up to 8 hours for 1 mask, for 1 month(April to May 2020) 1 off instructions for mask use and again as needed Weekly follow‐up emails Hotline available at all times during study periodChanging of mask if worn for more than 8 hours If guests in the home, wear mask Individualised support as needed via email or telephoneNone describedFace mask adherence:Self‐report(Yes / Partial / No) (Suppl 4) Average mask use per day Self‐assessed adherence with health authority guideline on social distancing and hygiene (Suppl)Face mask adherence: %Adhere: 46%Partial: 47% No: 7% Mean face masks used:Weekdays: 1.7Weekends: 1.3 Health authority guidance adherence not reported
Canini 2010Surgical face masksHouseholders (over 5 years)Limit transmission of influenza transmission by large droplets produced during coughing in householdsInitial supply of 30 masks:
for adults and children > 10: surgery masks with ear loops, 3 plys, anti fog
(AEROKYN, LCH medical products, Paris, France)
Children 5 to 10: face mask KC47127, (Kimberly‐Clark, Dallas, TX, USA)
Closed plastic bags for disposalMasks given immediately on home visit by attending general practitioner with demonstration of proper use and instruction to be worn for 5 days in presence of another household member or in confined space (e.g. car) and to change every 3 hours or if damaged.General practitionersFace‐to‐face individuallyHouseholds in FranceOne‐off provision of masks worn for 5 daysNone described.None described.Not described, but reported mask usage was measured34/51 (66%)
wore masks > 80% of the duration.
Reported mask‐wearing: 11 ± 7.2 masks during 4.0 ± 1.6 days with an average use of
2.5 ± 1.3 masks per day and duration of use of 3.7 ± 2.7 hours/day
Jacobs 2009Face masksHospital healthcare providers (nurses, doctors, and co‐medical personnel)Decrease risk of infection through limiting droplet spread through masksHospital‐standard disposable surgical
Mask MA‐3 (Ozu Sangyo, Tokyo, Japan); quantity not specifiedProvision of masks and instructions for useNot described, presumably research teamFace‐to‐faceTertiary care hospital in Tokyo, Japan
Face masks worn whilst on hospital property.77 daysNone described.None described.Self‐reported adherenceSelf‐reported adherence for both groups reported as good, with full adherence by 84.3% and remainder complying 79.2% to 98.7%.
Loeb 20092 active interventions
A. surgical masks
B. N95 respiratorsHealthcare workers (nurses)Reduce transmission of influenza in healthcare settings through coughing or sneezing with protective masksA. Surgical masks
B. N95 respiratorsProvision of masks or N95 respirators

Instruction in use and proper placement of devices

Fit‐testing and demonstration of positioning of N95 using standard protocol and procedure (details provided)

Qualitative fit‐testing using saccharin or Bitrex protocol[7]Provided by research team (not further described)
Fit‐testing by technician for N95In‐person face‐to‐faceTertiary hospitals in Ontario, Canada1 influenza season (12 weeks)

Use of mask as required[8] when providing care to or within 1 m of patient with febrile respiratory illness, ≥ 38 °C, and new or worsening cough or shortness of breath
Nurses to wear N95 when caring for patients with “febrile respiratory illness”Fit‐testing of nurses not already fit‐testedCeased before end of seasonAdherence audits during peak of season by trained auditor who stood short distance from patient isolation room18 episodes:
N95: 6/7 participants (85.7%) wearing assigned device versus 100% for masks
MacIntyre 20092 active interventions in addition to infection control guidelines
A. Surgical masks (SM)
B. P2 masks (P2)Householders with a child with fever and respiratory symptomsPrevent or reduce respiratory virus transmission in the community through non‐pharmaceutical interventionsA. 3M surgical mask, catalogue no. 1820;
St Paul, MN, USA for adults
B. P2 masks (3M flat‐fold P2 mask, catalogue no. 9320; Bracknell, Berkshire, UK)
A and B: health guidelines and pamphlets about infection controlProvision of masks and pamphlets and education about infection prevention and mask use
Telephone calls and exit interviews to record adherence to mask use
All groups: health guidelines, pamphlets about infection control were providedNot described, presumably research teamFace‐to‐face and by telephoneHouseholds in Sydney, Australia2 winter seasons (3 months and 6 months)
2 weeks of follow‐up
Masks to be worn at all times
when in same room as index child, regardless of
distance from childNone described.None described.Daily telephone calls to record mask use throughout day
Exit interviews about adherenceReported mask use:
Day 1
SM: 36/94 (38%)
P2: 42/92 (46%) stated wearing “most or all” of the time. Other participants were wearing face masks rarely or never.
Day 5: SM: 29/94 (31%)
P2: 23/92 (25%)
MacIntyre 20113 active interventions
A. Medical masks
B. N95 respirators fit‐tested
C. N95 respirators non‐fit‐testedHealthcare workersProtect HCWs by preventing transmission of influenza and other respiratory viruses from patients through mask wearingDaily supply of
A. 3 medical masks (3M medical mask, catalogue number 1820, St Paul, MN, USA)
2 respirators:
B. N95 fit‐tested mask (3M flat‐fold N95 respirator, catalogue number 9132) fit‐tested with 3M FT‐30 Bitrex Fit Test kit according to manufacturer's instructions (3M, St Paul, MN, USA)
C. N95 non‐fit‐tested mask (3M flat‐fold N95 respirator, catalogue number 9132)
Diary cards for usage recordingSupply of masks or respirators.
Instruction in when to wear it, correct fitting, and storage (in paper bag in personal locker)
Instruction in importance of hand hygiene before and after removal
For fit‐tested group: fit‐testing procedureMasks provided to hospitals.
Training of staff provided by 1 member of research team.Masks and training provided face‐to‐face, not described if training was individually or in groups.Emergency departments and respiratory wards in hospitals in Beijing, ChinaEntire work shift for 4 weeksTaken off for toilet and meal breaks and at end of shiftNone described.Mask ⁄ respirator use monitored by:
(i) observed adherence by head ward nurse recorded daily;
(ii) self‐report diary cards carried during day recording;
(i) no. hours;
(ii) usage.
Exit interviewsAdherence for usage was high for all and not significantly
different amongst arms.
Medical mask: 76%, 5 hours
N95 fit‐tested: 74%, 5.2 hours
N95 non‐fit‐tested: 68%, 4.9 hours
MacIntyre 20133 active interventions
A. N95 respirators at all times
B. N95 respirators targeted use
C. Medical masksHealthcare workers (nurses and doctors)Protect HCWs from respiratory infections from patients through mask useDaily supply of:
A. and B.
2 respirators
(3M Health Care
N95 Particulate Respirator; catalogue number 1860)
3M FT‐30 Bitrex Fit Test Kit
C. 3 masks
3 masks
(3M Standard Tie‐On Surgical Mask catalogue number mask 1817; 3M, St Paul, MN, USA)
Pocket‐sized diary card with tick boxes for mask useSupply of respirators
Instructions in use including times and fit
Fit‐testing procedure according to the manufacturer’s instructions (3M)
For targeted N95:
checklist of defined high‐risk procedures, including common aerosol‐generating procedures3M supplied respirators and masks.
Provider of instructions not specified.Masks and training provided face‐to‐face, not described if training was individually or in groups.Emergency departments and respiratory wards of tertiary hospitals in Beijing, ChinaFor 4 weeks,
A and B worn at all times on shift;
B. targeted (intermittent) use of N95 respirators only whilst performing high‐risk procedures or barrier.None described.None described.Self‐reported daily record of number of hours worked, mask or respirator use, number of high‐risk procedures undertaken collected by study staff.Adherence highest for targeted
N95 (82%; 422/516) versus N95 (57%; 333/581)
versus medical mask (66%; 380/572).
MacIntyre 20152 active interventions
A. Cloth masks
B. Medical masksHospital
healthcare workersPrevent respiratory infections in HCWs from patients through mask‐wearingA. 5 cloth masks for study duration (2‐ layer, cotton)
B. 2 medical masks daily for each 8‐hour shift for study duration (3 layers, non‐woven material)
All masks locally manufactured.
Written instructions on cleaning cloth masksCloth or medical masks to be worn at all times on shift.
Cloth masks to be washed with soap and water daily after shifts, and the process of cleaning to be documented.
Provision of written instructions for cloth mask cleaningResearchers arranged supply of masks and instructions and any training of staff assisting the delivery.Masks and written instructions provided face‐to‐face.Hospital wards in Vietnam4 weeks (25 days) of face mask useMasks not worn while in the toilet or during tea or lunch breaks.None described.Monitored adherence with mask use by

self‐report diary card and exit survey and interviews with a sub‐sample (ACTRN12610000887077)Mask‐wearing adherence:
cloth mask: 56.8% medical mask: 56.6%
Reported cloth mask washing: 23/25 days (92%)
MacIntyre 2016Medical mask useSick householders with ILI (index cases) and their well contacts of the same householdProtect well people in the community from transmission of respiratory pathogens
by contacts with ILI through mask use21 medical masks (3M 1817 surgical mask)
Diary cards for mask useSupply of masks
Instructions for mask wearing and hand‐washing protocol
Provision of diary cardsStudy staff member provided masks and instructions in use.Masks and instructions provided face‐to‐face and individually.Fever clinics of major hospitals in Beijing, China3 masks/day for 21 days
Mask wearing: whenever in the same room as a household member or a visitor to the household
Hand‐washing: before putting on and after taking offAllowed to remove their masks during mealtimes and whilst asleep and to cease wearing once symptoms resolvedNone reported.Self‐reported daily record of mask use using diary cardMask use: mask group: 4.4 hours; control group: 1.4 hours
Radonovich 20192 active interventions
A. N95 respirators (N95)
B. Medical masks (MM)Healthcare personnel of outpatient sites within medical centresPrevent HCP from acquiring
workplace viral respiratory infections and transmitting them to others by effective respiratory protection by N95 respirators which reduce aerosol exposure and inhalation of small airborne particles, meet filtration requirements, and fit tightlyA. N95 respirators:

3M Corporation 1860, 1860S, and 1870 (St Paul, MN, USA) or Kimberly Clark Technol Fluidshield

PFR95‐270, PFR95‐274 (Dallas, TX, USA)

B. Medical mask Precept 15320 (Arden, NC, USA) or

Kimberly Clark Technol Fluidshield 47107 (Dallas, TX, USA).

Reminder signs posted at each site

A portable computer equipped with data recording software (HandyAudit; Toronto, Canada) to document adherence (Radonovich 2016)Participants instructed to wear assigned protective devices whenever they were positioned within

6 feet (1.83 m) of patients with suspected or confirmed

respiratory illness and to don a new N95/MM with each patient interaction.

Hand hygiene recommended

to all participants in accordance with Centers for Disease Control

and Prevention guidelines.

Infection prevention policies

were followed at each study site.

Reminder signs posted at sites and emails sent.

Annual fit‐testing conducted for all participants.

Filtration testing performed on the device models in the study. Further details in protocol (Radonovich 2016).Centres provided device supplied by study to HCP.
Study personnel posted reminder signs and emails and conducted adherence observations.Face‐to‐face individual provision of devices and adherence observations
Onsite posting of signs
Other reminders by emailOutpatient sites within medical centres in USAAs instructed, for each new patient interaction during 12‐week period of peak viral respiratory illness each year for 4 years (total of 48 weeks)Fitting of N95 masksNone described.Reminder signage posted at study sites, and emails sent by study personnel.
Self‐reported daily device wearing of “always”, “sometimes”, “never”, or “did not recall"
Observation of device‐wearing behaviours as participants entered and exited care rooms conducted during unannounced, inconspicuous visits to randomly selected sites documented on portable computerDevice wearing:
N95: 89.4% reported “always” or “sometimes” versus MM: 90.2%
“Never”
N95: 10.2%
MM: 9.5%
Hand hygiene
Alzaher 2018Hand hygiene workshopPrimary school girlsTargeted school children to improve hand hygiene to reduce school absences due to upper respiratory infection and spread of infection in schools and to families6‐minute video‐clip of 2 siblings that attended school‐based health education about hand hygiene Short interactive lecture about:common infections in schools,methods of transmission, hand‐washing procedure using soap and water including when to wash hands Puzzle games related to hand hygiene Posters with cartoon princesses’ picture promoting hand‐washingDelivery of workshop and distribution of supporting materials (games and posters) to school and studentsStudy investigator delivered workshop.Delivered face‐to‐face in group format for the workshop 2 primary girls’ schools in Saudi Arabia1‐hour once‐off workshop; posters and games provided to schoolNot describedNot describedPosters in restrooms as reminders of hand‐washing hygiene during 5‐week follow‐up period after workshopNot reported
Arbogast 2016Multimodal hand hygiene intervention programme in addition to control of brief videoOffice buildings and the employees of health insurance companyReduce hand‐to‐mouth germ transmission from shared workspaces and workplace facilities and thereby healthcare claims and absenteeism through improved workplace hand hygieneAlcohol‐based hand sanitiser (PURELL Advanced, GOJO Industries Inc, Akron, OH, USA) installed as wall‐mounted dispensers, stands, or free‐standing bottles One 8‐ounce bottle of hand sanitiser (PURELL Advanced) per cubicle One 100‐count canister of hand wipes (PURELL Wipes) per cubicle Replenishment products stored in supply room(in addition to existing foam hand wash (GOJO Green Certified Foam Handwash) and an alcohol‐based hand sanitiser foam wall‐mounted dispenser (PURELL, GOJO Industries) already provided near the restroom exits prior to intervention) Identical soap in all restrooms Intervention and control group:brief (< 1‐minute educational video) about proper hand hygiene technique, for both washing and sanitising hands ‘‘Wash Your Hands’’, signage promoting hand hygiene adherence, was already posted next to restroom exits at both the control and intervention sites.Hand hygiene supplies installed in offices. Replenishment product was made easily available to individual employees upon request via a simple process. Monitoring of product shipments into sites Physical collection and full replacement of soap, sanitiser, and wipes Intervention and control group:educational video embedded at end of baseline online knowledge surveyNot described, presumably study investigators arranged installationsHand hygiene supplies provided in office environments and individually at staff cubicles/offices. Video provided individually via email.High‐traffic common areas of 2 US health insurance company offices (e.g. near elevators, at entrances) and appropriate public spaces (e.g. coffee area, break rooms, conference rooms, training rooms, lobbies, reception areas); individual staff cubicles of mostly open plan offices (average 309 square feet).Office restrooms13.5 months overall One‐off email video 11 days before study hand hygiene supplies installed. 13 months of provision of supplies 2 times evening collection and full replacement of products  Sanitiser installed in high‐use areas of the offices.Not describedEmployee survey at 4 months included questions about hand hygiene practice adherence. Monitoring of productshipments into the sites and physical collection of the soap, sanitiser, and wipes products 2 times in the study; collected samples were measured and usage rates wereestimated Intervention group employees: reported 40% more cleaning of work area regularly; significantly more likely to keep the hand sanitiser with them and use it throughout the day; significant increases in hand sanitiser use for at‐risk activities[9] Estimated use by average employee from sample collection:sanitiser 1.8 to 3.0 times/day,soap2.1 to 4.4 times/day,wipes at their desk 1.4 to 1.5 times/week  
Azor‐Martinez 2016Hand‐washing programmePrimary school children and their parents and teachersPrevent transmission of upper respiratory infections in schools and to families through non‐pharmaceuticalintervention of hand‐washing programme in schoolsBrochure about hand‐washing awareness and habits Workshop content materials Stories, songs, and classroom posters about hand hygiene and infection transmission Hand sanitiser (ALCO ALOE GEL hand sanitiser by Americo Govantes Burguete, S.L. Madrid, Spain containing 0.2% chlorhexidine digluconate, 1% phenoxyethanol, 0.1% benzalkonium chloride, 5% aloe barbadensis, 70% denat ethyl alcohol, excipients quantity sufficient for 100 mL alcohol 70%, pH 7.0 to 7.5) Informational poster about when and how to wash hands Written and verbal guidance to teachers, parents, and students on properties, possible side effects, and precautionary measures for gel use and storageBrochure sent to parents by mail with study information sheet. Workshop provided for pupils and teachers:frequent infections in schools, transmission and prevention, instructions on correct hand‐washing (water and soap, soaping > 20 s, drying hands),use of hand sanitisers and possible side effects Classroom activities linked to hand hygiene and infection transmission Reinforcement of hand hygiene by teachers Hand sanitiser dispensers fixed to walls with an informational poster about hand‐washing Supervision of younger children when using hand sanitiser and administration of sanitiser if needed Instruction of children in hand‐washing procedures after toilet and when dirty and correct hand sanitiser use[10]Brochure sent by school administration. Workshop and verbal and written information presumably provided by the study research assistant. Classroom activities provided by research assistant and teachers. Supervision and administration of hand sanitiser for younger children by teachers Brochure sent by mail to individual parents. Workshops and classroom activities delivered in groups face‐to‐face. Teacher reinforcement of hand hygiene provided to class face‐to‐face. Hand sanitiser use supervision was provided individually and face‐to‐face.Primary school classes in Spain (details not provided)8 months overall One‐off brochure and installation of hand sanitiser dispensers 2‐hour workshop held 1 month before study commencement Fortnightly classroom activities As required, teacher supervision and administration of hand sanitiser Daily reinforcement of hand hygiene by teachersSupervision and administration of hand sanitiser as needed by teachers, especially for younger childrenNot describedDaily reinforcement by teachers of hand hygiene Fortnightly support by research assistant promoting hand‐washing Self‐reported correct hand‐washing procedure (water and soap, soaping > than 20 s, drying hands)Self‐reported correct hand‐washing included in analysis but not separately reported.
Azor‐Martinez 2018Educational and hand hygiene programme 2 active interventions:A. soap and waterB. hand sanitiserDay care centres and their attending children, their parents, and DCC staffPrevent transmission of respiratory infections by improved hand hygiene of children, parents, and staff through hand‐washing practices and use of hand sanitiser due to its bactericide and virucide propertiesA. Liquid soap (no specific antibacterial components (pH = 5.5))ORB. Hand sanitiser (70% ethyl alcohol (pH = 7.0 to 7.5)) for home use and in dispensers for school classroom Workshop content handout Stories, songs, and posters about hand hygiene and infection transmissionInstallation of liquid soap or hand sanitiser dispensers in classrooms Supervision and administration of hand sanitiser if required 3 hand hygiene workshops for parents and DCC staff:1. Hand‐washing practices, hand sanitiser use, possible side effects andprecautionary measures (HSG only)2. RIs and their treatments3. Fever Instructions to children, parents, and DCC staff on usual hand‐washing practices and protocol[11] Classroom activities (stories and songs) about hand hygiene and infection transmissionWorkshop delivered by researchers. Research assistant provided hand hygiene materials to DCCs and parents. Parents and staff supervised and administered sanitiser where indicated.Workshops delivered face‐to‐face in groups to parents and staff. Workshop content emailed to attendees individually. Individual face‐to‐face supervision of hand sanitiser use, as indicated   Classroom of DCCs (in Spain) for child interventions Workshops provided at DCCs.8 months overall Initial 1‐hour workshop 1 month before study commencement 3 further identical sessions/DCC provided again 1 month apart Fortnightly classrooms and DCC activities One‐off installation of dispensers As‐needed supervision of hand sanitiser use Dose of sanitiser: 1 to 2 mL/disinfectionAdministration of hand sanitiser in the case of young children DCC staff could attend training at other DCC if unable to attend at own DCC.Not describedNot described Reported that no monitoring of adherencethrough continuous observation of hand hygienebehaviours was done, but amount of hand sanitiser was measuredFamilies or DCC staff, or both, used 1660 L of hand sanitiser, estimated use by each child of dose 6 to 8 times/day.  
Biswas 2019Hand sanitiser and respiratory hygiene educationPrimary schools and their students and staffReduce community‐wide influenza virus transmission by improving hand‐washing and respiratory hygiene and use of sanitiser in schoolchildren as contributors to community‐wide virus transmissionHand sanitiser(63% ethyl alcohol) in colourless, transparent 1.5‐litre local plastic bottles (manufactured by a local pharmaceutical company and was available commercially in Bangladesh (price: USD 5.75/L)) Video clip on respiratory hygiene practices Behavioural change materials – 3 colour posters (see Appendix of paper) Curriculum materials for hygiene classesInstallation of hand sanitiser in wall dispensers in all classrooms and outside all toilets, refilled by field staff as needed Encouragement of use of sanitiser at 5 key times during the day[12] Hand and respiratory hygiene education provided.[13] Integration of hygiene messages into school’s hygiene curriculum Delivery of video clip on respiratory hygiene practice Behaviour change materials distributed and placed around schools. Use of sanitiser by classroom teachers after training Training of selected teachers in consultation with head of school and management committee in key messages Communication of key messages by the selected teachers to other teachersSelected teachers responsible for dissemination of intervention messages throughout were trained over 2 days in these messages, behaviour change communication, sanitiser use, and practices for preventing spread of respiratory secretions. Classroom teachers conveyed intervention messages during regular hygiene classes. Field staff replaced supplies as needed.Hand sanitiser and education materials provided to schools. Education provided in classrooms in groups and face‐to‐face.Primary schools (in Bangladesh) Sanitiser in each classroom and outside toilets Education in classroom10 weeks Intervention messages conveyed in classrooms 3 times/week.Refills provided as needed.Not describedStructured field observation by 2 field staff of 5 hours/school observing hand‐washing and respiratory hygiene behaviours of children at 2 different locations in a classroom or outside Every other day, field staff measured the level of hand sanitiser in the morning and in the afternoon to calculate amount of hand sanitiser used/day/school and enrolled children.Hand‐washing observed opportunities:IG 604/921 (66%) versus CG 171/802 (21%) Hand sanitiser used in 91% of observed hand‐washing events in intervention schools. Averageconsumption of hand sanitiser/child/day: 4.3 mL Observation of proper cough or sneeze etiquette: IG: 33% versus CG: 2%
Correa 2012 Alcohol‐based hand rubsChildcare centres and their staff and childrenReduce incidence and transmission of infection in children by improved hand hygiene where water is scarce including provision of ABH and training in hand hygiene teaching techniquesDispensers of alcohol‐based hand rubs with ethanol 62.0% (PURELL, GOJO Industries, Akron, OH, USA) Workshop materials[14] Visual reminders on ABH techniques in bathrooms and next to dispensersABH and trainingon proper use to staff and children Pre‐trial ABH use workshop to teachers that followed recommended HH teaching techniques and instructed teachers to add ABH to routine HH and give preference to hand‐washing with soap and water if hands visibly soiled Continuous refilling of ABH ABH technique refresher workshops (8/centre) Monitoring of safety, proper use of ABH, amount of ABH usedLocal representativeof GOJO Industries Inc.provided dispensers and dispenserinstallations free of charge. Fieldwork team delivered other components.Face‐to‐face training and provision of materials; group trainingChildcare centres in Colombia (centres or community homes)ABH in centres, classrooms, and common areas depending on size Visual remindersin bathroomsand next to dispensers Workshops and training presumably provided in centres.  8 months overall 1 ABH dispenser per centre with < 14 children;1 per classroom in larger centres; 1 per classroom +1 for common areas in centres with > 28 children 1 workshop pre‐trial to staff Monthly 30‐minute ABH technique refresher training (8 per centre) Biweekly monitoringRefilled ABH as neededNot describedVisual reminders and monthly refresher training Monitoring of safety, proper use of ABH, amount of ABH used Semi‐structured survey on completion of teachers' perceptionsabout changes in HH practices and use of HSW and ABH.Measurement of consumptionof resources and costs related to ABH use and HSWTeachers at 7intervention centres reported almostcomplete substitution of HSW with ABH, and HSW decreased from 3 times per day to 1 per day, and ABH rose to 6 per day. Teachers at remaining 14 centres reported partial substitution of HSW with ABH.Controls reported HSW 3 times per day. Median number of ABH applications per childrose from 3.5 to 4.5 in preschools and 3.5 to 5.5 in community centres.
DiVita 2011Household hand‐washing promotionHouseholders with index patient with ILIPrevent influenza transmission in households in resource‐poor settings through provision of hand‐washing facilities and use of them at critical times for pathogen transmissionHand‐washing stations with soap Provision of hand‐washing stations Hand‐washing motivation to wash at critical times for pathogen transmission (e.g. after coughing or sneezing)Not specifically described, presumably the researchersFace‐to‐face provision of facilities in households "Motivation" not describedHousehold in BangladeshOver 2 influenza seasons One‐off provision of hand‐washing facilities Frequency of “motivation” not describedNot describedNot describedNot describedNot described
Feldman 20162 active interventions
 A. Hand disinfection with chlorhexidine gluconate + hygiene education
 B. Hygiene education Naval ships and their sailorsReduced infection transmission and improved hand hygiene in sailors who are at increased risk due to closed environments, contact with shared surfaces, and poor HH cultureSeptadine solution (Floris, Misgav, Israel) 70% alcohol and 0.5% CHG; inactive materials: purified water, glycerin, propylene glycol, and methylene blue  Installation of CHG disinfection devices on ships alongside regular soap and water Supply and replenishment of CHG (sent to ships regardless of replenishment demands) Hygiene instruction by a naval physician (to both intervention groups and study control group)Provision of CHG presumably by study team and funds Hygiene instruction by naval physicianCHG sent to ships directly. Mode of hygiene instruction not described.Navy fast missile boats and patrol boats of naval base in Israel Dispensers installed in key locations onboard (adjacent to heads (toilets), mess decks(dining rooms), common areas).4 months Unlimited supply of CHG replenished on demand for 4 to 5 months. Automatic amount dispensed: 3 mL CHG replenished on demand.Not describedTotal amount of CHG dispensed was tallied.Mean volume CHG:8.2 mL per sailor per day (projected yearly cost USD 45 per sailor)
Gwaltney 1980 A. Virucidal hand preparation
 B. Placebo (no control)Healthy young adultsReduce infection rates by interrupting viral spread by hand or self‐inoculation routeA. Virucidal hand preparation:aqueous iodine (2% iodine and 4% potassium iodide) B. Placebo: aqueous solutionof food colours (Kroger; Kroger Co., Cincinnati, OH, USA) mixed to resemble the colour of iodine with 0.01% iodine and 0.02% potassium iodide to give an odour of iodine MasksImmersion of each finger and thumb of both hands to proximal interphalangeal joint (interphalangeal joint of thumb) into designated preparation for 5 seconds then air‐dried for 5 to 6 min Exposure of recipients to donors either immediately after treatment or after 2‐hour delay by hand contact with donor stroking fingers for 10 s Masks worn by donors and recipients during procedure. Recipients placed in single isolation rooms after second exposure till end of experiment.ResearchersFace‐to‐face and individuallyUS universityExposure to donors on 3 consecutive days (days 2, 3, and 4) after initial exposureNot describedNot describedReported knowledge of hand preparation use as active, placebo, or don't knowActive (n = 24):6 active
2 placebo16 don't knowPlacebo (n = 22):6 active7 placebo9 don't know
Hubner 2010Alcoholic hand disinfectionEmployees (administrative officers)Reduce absenteeism and spread of infection in administration employees with frequent customer contact and work with paper documents through improved hand hygiene2 alcohol‐based hand rubs (500 mL bottles) for desktop use to ensure minimal effort for use:1. Amphisept E (Bode Chemie, Hamburg, Germany) ethanol (80% w/w) based formula with antibacterial, antifungal, and limited virus inactivating activity.2. For participants with skin problems:Sterillium (Bode Chemie, Hamburg, Germany) 2‐propanol (45% w/w), 1‐propanol (30% w/w), and mecetronium etilsulfate (0.2% w/w), with a refatting effect and has activity against bacteria, fungi and enveloped viruses. Hand cream: Baktolan balm, water‐in‐oil emulsion with no non‐antibacterial properties (Bode Chemie, Hamburg, Germany)Provision of hand rub and instruction on use as needed at work only and in accordance with prevailing standard[15]: at least 5 times per day, especially after toileting, blowing nose, before eating, and after contact with ill colleagues, customers, and archive materialPresumably provided or arranged by study teamIn person to staffAdministration offices in Germany Hand rubs used at desk or work (not outside of work).12 months overall Hand rub used as much needed for complete wetting of the hands (at least 3 mL or a palmful)[16] at least 5 times per day.Hand rub use especially after toileting, blowing nose, before eating, and after contact with ill colleagues, customers, and archive materialNot describedSelf‐reported adherence with hand hygiene measuresReported mean hand disinfection frequency times per day:> 5: 19%3 to 5: 59.8%1 to 2: 20.5%< 1: 0.7% 
Ladegaard 1999(translated from Danish)Hand hygiene programmeDaycare centres and their staff, children, and parents of childrenReduce risk of infection in child care through increased hygienic education of daycare professionals, motivation of daycare facilities for regular hand hygiene, and informing parents about hand hygienePersonnel guide on recommendations for: hygiene, ventilation, out‐of‐stay care, stricter hygienic regulations in cases with selected diseases Fairy tale and poster “The Princess Who Won't Wash Hands” Colouring in drawings “Wash hands” song and rhymes T‐shirt for children with the inscription “Clean hands ‐ yes thank you” Diploma for children and book “The Princess Who Won't Wash Hands” to also be used by parents with their child Informational leaflet for parents in envelopeStaff meeting in each DCC and training in microbiological cause of infection spread guided by National Board of Health and Hygiene Education of children in hand‐washing (about bacteria and why and when to wash hands) Practical hand‐washing classes with 4 to 5 children at a time Provision of t‐shirt, book, and diploma to children Provision of leaflet for parentsResearch team presumably provided training.  Face‐to‐face with training and activities by group with staff and children Information sent home to parents via children.Onsite in DCCs  2‐month intervention period 1‐hour training of childrenNone described.None described.None described.None reported.
Little 2015Web‐based hand‐washing interventionHouseholders (over 18) who were general practice patientsPrevent transmission of respiratory tract infections through improved hand hygiene to reduce spread via close contact (via droplets) and hand‐to‐face contactWebsite‐based programme: provided information about the importance of influenza and role of hand‐washing;developed a plan to maximise intention formation for hand‐washing;reinforced helpful attitudes and norms;addressed negative beliefs(URL provided for demonstration version no longer active; see www.lifeguideonline.org)Provision of link to website for direct log in Automated emails prompted participants to use sessions and complete monthly questionnaires and maintain hand‐washing.Researchers delivered web‐based programme and emails.Online individuallyHouseholds in England4 months overall 4 weekly web‐based sessions Monthly email questions to maintain hand‐washing over 4 monthsTailored feedback provided within web programmeNone described.Emailed questions monthly to maintain hand‐washingNone reported.
Luby 2005Hand‐washing promotion at neighbourhood level with 2 interventions at household level A. Antibacterial soap
 B. Plain soapNeighbourhoods and their householdsImprove hand‐washing and bathing with soap in settings where communicable diseases are leading causes of childhood morbidity and mortalitySlide shows, videotapes, and pamphlets illustrating health problems from contaminated hands and specific hand‐washing instructions Soaps: 90‐gram white bars without brand names or symbols, same smell with identical generic white wrappers with serial numbers matched to households A. Households: 2 to 4 white bars of 90‐gram antibacterial soap containing 1.2% triclocarban (Safeguard Bar Soap: Procter & Gamble Company (Cincinnati, OH, USA) B. Households: plain soap (no triclocarban) Soap packetsHand‐washing promotion to neighbourhoods:Neighbourhood meetings of 10 to 15 householders (mothers) from nearby homes and monthly meetings for men Soap to households Fieldworker home visits: discussed importance of and correct hand‐washing (wet hands, lather them completely with soap, rub them together for 45 seconds, and rinse off completely) technique and promote regular hand‐washing habits[17] Encouragement of daily bathing with soap and waterResearch team in collaboration with Health Oriented Preventive Education (HOPE)[18] Fieldworkers were trained in interviewing and hand‐washing promotion.Face‐to‐face in small groups and individuallyNeighbourhoods and homes in Karachi, Pakistan1‐year weekly household visits 30‐ to 45‐minute neighbourhood meetings 2 to 3 times/week first 2 months then weekly for months 2 to 9, then monthly Monthly men’s meetings first 3 months Weekly household visitsSoap replaced regularly.None described.None described, though soap use measured.Households' mean use of study soap per week: 3.3 barsAverage use per resident per day: 4.4 g
Millar 2016 additional details from Ellis 2010Skin and soft‐tissue infection prevention intervention in addition to SSTI brief on entry also provided to control
 A. Enhanced standard
B. ChlorhexidineMilitary traineesImprove personal hygiene practices to prevent infection, especially acute respiratoryinfection in military trainees who are at increased riskA. Enhanced standard: supplemental materials (a pocket card and posters in the barracks) B. CHG: CHG‐based body wash (Hibiclens, Mölnlycke Heath Care, Norcross, GA, USA)Provision of education and hygiene‐based measures in addition to standard SSTI prevention briefupon entry: Enhanced standard:supplementalmaterials CHG: as for enhanced standard group, plus a CHG‐based body wash and instructions for useNot described, presumably the researchersFace‐to‐face and individually for body wash and pocket card Mode of education not described.US military training baseOne‐off education on entry to training CHG: use of wash 1 per week for entire training period (14 weeks)None described.None described.None described.None described.
Morton 2004 Healthy hands (alcohol gel as hand‐washing adjunct)  Elementary schools and their children and staffPrevent infections in elementary school‐age children who are particularly vulnerable through adjunct use of alcohol gel and education based on Health Belief Model (HBM) (Kirscht 1974)Alcohol gel and dispensers:AlcoSCRUB (60% ethyl alcohol) supplied by Erie Scientific Company, Portsmouth, NH, USA ‘‘Healthy Hands Rules’’ protocol[19](Figure 3 in paper) Healthy Hand Resource Manual for school nurse, available for parents Monthly newsletters to parents ‘‘Healthy Hands’’ refrigerator magnet for families (see Figure 2 in paper) Informational letter to local primary care providers, paediatricians, family practitioners, and advanced practice nurses “Germ Unit” curriculum and materials including Germ models and Glo GermHealthy hands protocol introduced after "Germ unit" education in classes Daily reminders to children on public address system (in first week) then weekly reminders Review of protocol in each classroom after vacation by school nurse 2 classroom visits from school nurse “Healthy Hands” magnet provided to parents and guardians. “Hand Checks on Wednesdays” to identify adverse effects of gel  Gel provided by suppliers. Research team provided educational aspects. Classroom teachers responsible for encouraging use of gel and reinforcing protocol School nurse assisted in monitoring and hand checks for adverse effects.  Face‐to‐face training in classes and individual information giving and monitoringElementary schools in USA Wall‐mounted near door entrance of each classroom at age‐appropriate height46 days 0.5 mL dispensed per application. Use of “special soap” according to “Healthy Hands Protocol” (Figure 3 in paper) Reinforcement teaching provided if gel usage indicated that it was needed. Germ unit education tailored for each grade level.1 student was concerned gel was making her sick, so school nurse provided additional classroom visit to allay concerns.Usage of gel calculated.5 gel applications per day 1 dispenser lasted 1 month.
Nicholson 2014Hand‐washing withsoapHouseholds with 5‐year‐olds and their mothersTargeted 5‐year‐old children and their mothers as change agents to reduce incidence of respiratory infections (and diarrhoeal disease) through hand‐washing using behaviour change principles (Claessen 2008), including social norms for child and mother (Perkins 2003), using fear of contamination and disgust (Curtis 2001), peer pressure (Sidibe 2003), morale boosting, and networking supportInitial supply of 5 bars of free soap (90‐gram Lifebuoy bars) replenished on submission of empty wrappers. Environmental cue reminders (wall hangers, danglers) Rewards (e.g. stickers, coins, toy animals)Provision of soap and social marketing programme (Sidibe 2009) (Lifebuoy branding) to educate, motivate, and reward children for HWWS at key times Weeks 1 to 17: hand‐washing occasions, germ education, soap’s importance in germ removalWeek 18 onward: encouragement of HWWS on 5 key occasions supported by environmental cues "Classrooms" for children Home visits for mothers Parents’ evenings to boost morale, build networks, and run competition for adherence, assignment completion, and folder decoration Establishment of a "Good Mums" club for sharing HWWS tips Rewards provided by mothers. Children encouraged to advocate HWWS within families before meals. Establishment of social norms for child and mother with pledges in front of peersDedicated team of "promoters" delivered education and home visits. Mothers provided supplied rewards.Face‐to‐face in groups Individually by mother to child"Classrooms" held in community buildings Home visits of households in Mumbai, India41 weeks Weekly "classrooms" after school and home visits HWWS encouraged 5 key occasions: after defecation, before each of 3 meals, and during bathing. Week 18 onward: hand‐washing on 5 occasions for 10 consecutive days 6 weekly parents’ meetingsMothers were asked to provide and share hand‐washing tips with other mothers, competitions held for mothers.Technical difficulties with "soap acceleration sensors" to measure HWWS behaviours prevented successful use.Registers for "classrooms" and home visits where 3‐week gaps in attendance triggered supervisors to ask participants to resume or be withdrawn Monitoring of soap resale on open market by use of unique identifiers on soap wrappers and twice weekly checks in local shops Collection of used soap wrappers as soap consumption measureSoap consumption:IG versus CG:235 g versus 45 g
Pandejpong 20123 active interventions (no control) different time‐interval applications of alcohol hand gel A. Every 60 min B. Every 120 min C. Once before lunchPreschool classes (students and teachers) and their parentsTargeted preschool children who can have high infection rates in ILI; have close interaction so at risk of airborne, droplet, and contact transmission; and are of increasingly younger ages through hand gel as a single strategy of convenient and effective disinfection 1 container of alcohol hand gel per classroom (active ingredients: ethyl alcohol, 70%; chlorhexidine gluconate,1%; Irgasan (triclosan), 0.3%) Cost of hand gel every 60minutes was USD 6.39 per child per 12‐week period Leaflet describing risk factors for ILI for each familyTeachers instructed to:assist each child with dispensing hand gel at requiredtime interval,store hand gel properly, and refill gel as needed. Monitoring of hand gel use at specified times Teachers supervised, stored, and refilled hand gel. Instructions to teachers presumably provided by researchers. Leaflets distributed through school. Monitoring of use by 2 research assistantsFace‐to‐face to schools, teachers and children Individual assistance to children with hand gel Leaflets given to each family.Kindergarten school in Bangkok, Thailand12 weeks overall 1 pump of gel per child per disinfection round at 1 of 3 time intervals of school day:A. every 60 minB. every 120 minC. once only before lunch, the school standard for hand hygiene None described.Students whose families declined to participate were not askedto use alcohol hand gel. These students remained in their classroomsand continued to follow the school standard for handhygiene.2 researchassistants monitored hand gel use every 60 or 120 minutes for the duration of study. Classroom teachers were required to co‐sign after each disinfectionround.Reported that adherence was ensured for each interventiongroup Cost of hand gel every 60minutes was USD 6.39 per child per 12‐week period.
Priest 2014Hand sanitiser provision (in addition to hand hygiene education session also provided to control group)Primary schools and their students, teachers, and administrative staffReduce person‐to‐person community transmission of infectious disease by targeting improved and additional hand hygiene of school children through supervised hand sanitiser provision as an alternative to improving and maintaining bathroom facilities ‘‘No touch’’ dispensers(> 60% ethanol) for each classroom that dispensed dose when hands were placed under an infrared sensor Supply of top‐up sanitiser as needed Dispensers installed into each classroom. Teachers asked to ensure that the childrenused sanitiser at particular times and to oversee general use (McKenzie 2010). Weekly classroom visits to top‐up of sanitiser and measure quantity used 30‐minute in‐class hand hygiene education session provided (also to control group) plus instruction in hand sanitiser use.School liaison research assistants topped‐up sanitiser. TeachersInstallation of dispensers to classrooms Supervision of children by teachers delivered face‐to‐face individually and as a class.City schools in New Zealand20 weeks (2 school terms) Sanitiser to be used by students at least after coughing/sneezing, blowing their nose, and as they leave for morning break and forlunch break. Approximately 0.45 mL of sanitiser dispensed per wash. Weekly top‐up of sanitiser Children were able to use the sanitiser at any time they wished as well as at key times (McKenzie 2010).Change of sanitiser after week 10 to flavourless type of the same % ethanol in 41 of 396classrooms (10%) (in 9 of 34 schools)due to children tasting it when eating, affecting use. Weekly classroom visits by school liaison research assistants who recorded quantity of sanitiser used Total amount of sanitiser per classroom was measured. adherence defined as dispensing a volume equivalent to at least45 mL per child of hand sanitiser solution over the trial period.100% dispensing 45 mL per child Average hand sanitiser dispensed/child for 34schools: 94 mL Median classroom difference in sanitiser usage between first 10 weeks and second 10 weeks amongst classes that switched products was 220 mL. 
Ram 2015Soap and intensive hand‐washing promotionHousehold compounds and its householders (adults and children) that had a householder with ILIReduce household transmission of ILI and influenza by promoting hand‐washing in households with householder with ILI as other householders who are well are at highest risk of exposure due to crowded and poorly ventilated homes.Followed constructs of Social Cognitive Theory and the Health Belief Model (Glanz 2008) and behaviour change communication using social marketing conceptsHand‐washing station in central location of each compound using:large water container with a tap;plastic case for soap;bar of soap. Cue cards depicting critical times for hand‐washing:after coughing or sneezing;after cleaning one’s nose or child’s nose,after defecation;after clearing a child who has defecated;before food preparation or serving;before eating.Hand‐washing station in each compound Didactic and interactive group‐level education and skills training describing influenza symptoms, transmission, and prevention, promoting health and non‐health benefits of hand‐washing with soap and identification of barriers and proposed solutions to hand‐washing with soap Daily surveillance including weighing of soap and replacing if ≥ 20 g and resupply of water in container if needed Posting of cue cards Asking householders to demonstrate hand‐washing with soap techniqueIntervention staff arranged provision of hand‐washing station and presumably provided education. Intervention staff conducted daily surveillance and reinforcement visits.All elements delivered face‐to‐face but at compound (facilities), group (education), and individual levels (reinforcement).Household compounds in a rural area of Bangladesh consisting of several households with common courtyard, shared latrine, water source, and cooking facilitiesInitiation of intervention within 18 hours of study enrolment, then daily visits until 10 days following resolution of index case patient’s symptoms Day 1 set up of hand‐washing stationDaily surveillance included observation of individual hand‐washing reinforcement and modelling as needed.None described.Daily surveillance of facilities and reinforcement and modelling of hand‐washing behaviours including observed hand‐washing Cue cards in common areas of courtyard Presence or absence of soap during each of first 10 days of surveillance from 180 household compounds Patterns and amount of soap use measured.[20]Soap present for at least 7 days in all compounds and on all 10 days in 133 compounds (74%). Soap and water together were present 7 or more of first 10 days in 99% of compounds, with water and soap observed together on all 10 days in 99 compounds (55%) Soap consumption per capita:median: 2.3 gmaximal: 5 g (on Day 7) 
Roberts 2000 Education about infection control measures, hand‐washing, and aseptic nose wipingChildcare centres and their staff and childrenReduce transmission of respiratory infections in childcare centres through improved infection control proceduresGloGerm (GloGerm, Moab, UT, USA) Newsletters to staff Songs and rhymes on hand‐washing Plastic bags (sandwich bags available at supermarkets) to cover hand for nose wipingStaff training in good health (developed by Kendrick 1994) and practical exercise of hand‐washing with GloGerm Fortnightly visits and newsletter to reinforce training and to communicate techniques Recommended hand‐washing technique as per guidelines of the time[21] and after toileting, before eating, after changing diaper (staff and child), and after wiping nose unless barrier used Teaching of technique to children and wash hands for infantsTraining and reinforcement activities provided by 1 of the researchers. Teachers delivered training to children based on their training. Face‐to‐face in groups for training and classes and individually as needed to children or staffChildcare centres in Canberra, Australia  8 months overall 3‐hour training in evening or 1‐hour during lunch for new staff after study start Duration of hand‐washing: “count to 10” to wash and “count to 10” to rinseTraining for new staff provided as needed.None described.6‐weekly adherence measured by recorded observation of recommended practice for 3 hours in the morning in each centre, graded by quantiles of frequency of recommended hand‐washing by children.Adherence was reported only in relation to analysis of outcomes. High adherence reported for nose wiping and child hand‐washing.  
Sandora 2005 Healthy Hands Healthy FamiliesFamilies with an index child in out‐of‐home childcareReduce illness transmission in the home through multifactorial campaign centred on hand hygiene education and hand sanitiserAlcohol‐based hand sanitiser: active ingredient: 62% ethyl alcohol (PURELL Instant Hand Sanitiser; GOJO Industries, Inc, Akron, OH, USA) Hand hygiene educational materials at home (fact sheets, toys, games)Supply of hand sanitiser and hand hygiene materials Biweekly telephone calls Biweekly educational materials Study investigatorNot stated whether materials mailed or delivered in personHomes in USA Sanitiser use in home5 months overall Biweekly educational materials Sanitiser dispensed 1 mL each pump.None described.None described.Recorded amount of hand sanitiser used (as reported by the primary caregiver)Median frequency of reported times of hand sanitiser use: 5.2 per day 38% used > 2 ounces of hand sanitiser per fortnight = 4 to 5 uses per day
Savolainen‐Kopra 2012further details from Savolainen‐Kopra 2010STOPFLUEnhanced hygiene2 active interventions IR1. Soap and water washIR2. Alcohol‐based hand rubOffice workers of office work unitsPrevent transmission of respiratory infections in workplaces through enhanced hand hygiene with behavioural recommendations to reduce transmission by droplets during coughing or sneezingIR1: Liquid hand soap (“Erisan Nonsid” by Farmos Inc., Turku,Finland) IR2: in addition:Alcohol‐based hand rub, 80% ethanol (“LV” by Berner Inc., Helsinki, Finland) Bottles of hand hygiene product (free of charge) to be used at home and in the office (IR2). Written instructions on hygiene for further referenceToilets equipped with liquid hand soap (all groups) or alcohol‐based hand rub (IR2). Guidance on other ways to limit transmission of infections, e.g. frequent hand‐washing in office and at home, coughing, sneezing into disposable handkerchief or sleeve, avoiding hand‐shaking Visits to work clusters and monitoring of materials availability Monthly electronic “information spot” about viral diseases for motivation to maintain hygiene habits Adherence activitiesIn collaboration with occupational health clinics servicing the corporation Specially trained research nurse provided guidance and visited worker clusters throughout intervention period.In‐person provision of soap or hand rub Guidance and written instructions given personally. Face‐to‐face visits by study nurseOffice work units in corporations in Helsinki, Finland15 to 16 months overall Monthly visits by nurse throughout  Nurses assisted with any practical problems with intervention as they arose. New employees received guidance on hand hygiene and habits.None described.Adherence assessed byan electronic self‐report survey of transmission‐limiting habits 3 times (more details in protocol). Use of soap (IR1) and alcohol‐based disinfectant(IR2) forpersonal use was recorded. Study nurse checked availability of soap and alcohol rub.Avoiding hand‐shaking became more common and remained high in both groups. Recorded use for personal use smaller than predicted use based on hand hygiene instructions.Soap or disinfectant usage per participant:IR1: 6.1IR2: 6.9  
Stebbins 2011“WHACK the Flu”(hand sanitiser and training in hand and respiratory hygiene)  Elementary schools and their students and homeroom teachersTargeted school‐aged children as important sources of influenza transmission through improved cough etiquette and hand hygiene in schools including sanitiser as potential inexpensive non‐pharmaceuticalinterventionsHand sanitiser dispenserswith 62% alcohol‐based hand sanitiser from PURELL (GOJO Industries, Inc, Akron, OH, USA) automatically dispensing 1 doseDelivery of grade‐specific presentations on “WHACK the Flu” concepts and proper hand‐washing technique and sanitiser use:(W)ash or sanitise your hands often; (H)ome is where you stay when you are sick; (A)void touching your eyes, nose and mouth; (C)over your coughs and sneezes; and (Keep your distance from sick people(provided URL no longer active) Desired frequency of hand wash use taught to student (see When and how much) Installation of hand sanitiser dispensers Refresher training at each school Reinforcement of message and monitoring of sanitiserProject staff provided education. Home room teachers reinforced message and monitored proper use of sanitiser.Face‐to‐face at schools, presumably as a group in classesElementary schools (Pittsburgh, USA) Dispensers installed in each classroom and all major common areas.Whole intervention over 1 influenza season One‐off installation of hand sanitiser dispensers One‐off 45‐minute education presentation and one‐off refresher training at onset of influenza season Goal of use of 1 dose (0.6 mL) of sanitiser 4 times per day[22]Encouraged to wash hands or use additional doses of hand sanitiser, or both, as neededNone reported.Monthly teacher surveys of observed NPI‐related behaviour in their students before, during, and after influenza season Measurement of hand sanitiser use at 2‐week intervals throughout the intervention periodTeacher surveys of observed classroom NPI behaviour indicated successful adoption and maintenance of behaviours throughout influenza season. Average sanitiser use: 2.4 times per day
Talaat 2011Intensive hand hygiene campaignSchools and their students, teachers, and parentsReduce or prevent transmission of influenza viruses amongst children through intensive hand hygiene intervention campaignSoap supplied as needed. Grade‐specific student booklets each including a set of 12 games and fun activities that promoted hand‐washing Hand hygiene activities materials including:games (e.g. how to escape from the germs);puzzles;soap activities (e.g. soap drawing);song specially developed to promote hand hygiene Teachers’ guidebook including detailed description of the students’ activities and methods to encourage students to practice these activities. Posters with messages to wash hands with soap and water upon arriving at school, before and after meals, after using the bathroom, and after coughing or sneezing. Informational flyers for parents reinforcing the messages delivered at the schools.Establishment of a hand hygiene team in each school Provision of hand hygiene activities:weekly exercises (e.g. games, aerobics, songs, experiments); school activities, (e.g. obligatory hand‐washing under supervision, morning broadcast, parent meetings, students‐parents information transfer);specific school initiatives: (e.g. competitions and awards, hand‐washing committee, school trips to soap factory and water purification plant) More details in Table 1 of paper Song played regularly. Social worker weekly visits Distribution of flyers to parentsHand hygiene team (3 teachers from social studies, arts, and sports and the school nurse) ensured that all pre‐designed activities for the hand hygiene campaign were implemented. 6 independent social workers visited the schools.Delivered face‐to‐face in groups and individuallyElementary schools (grades 1 to 3) in Cairo, Egypt In school environment and classrooms Poster near sinks in classrooms and on playground12 weeks overall Weekly hand hygiene campaign activities Weekly visits by social workers Twice‐daily obligatory supervised hand‐washing required by students for about 45 seconds, followed by proper rinsing and drying with a clean cloth towel.Soap and hand‐drying material provided by school administration if children did not bring their own as was the custom or families could not afford it. Schools could create own motivating activities such as selecting a weekly hand hygiene champion, developing theatre plays, and launching school contests for drawings and songs.None described.Observation by social workers of hand hygiene activities, availability of soap and drying material, and students’ hand‐washing during the day Schools created own activities to improve adherence.About 93% of the students had soap and drying material available. All but 2 intervention schools “had a rigorous system of ensuring that schoolchildren were washing their hands at least twice daily”.
Teesing 2021(additional sources: Teesing 2020a and Teesing 2020b)HANDSOME multimodal nursing home HH adherence interventionNH management staff and nurses and nursing students (with or of 3 or 4‐year nursing degree) and residentsChange hygiene policy and individual HH behaviour of nurses through multimodal intervention designed specifically for nursing homes based on literature, interviews at nursing homes and intervention mapping principles, the principle of repetition and informal discussions with members of over 20 nursing home organisations in an iterative process See protocol for more details of intervention mapping process using determinants and methods to develop strategies for intervention componentsMaterials for lessons about WHO‐defined 5 moments for HH[23] using HANDSOME novel method:‘Room In’ (moment 1), ‘Room Out’ (moments 4 and 5 combined), ‘Before Clean’ (moment 2), and ‘After Dirty’ (moment 3)[24] Nurse’s watches and certificates earned on completion of e‐learning Paint for washing hands exercise 28 stickers representing barriers to HH in 4 themes (facilities, forgetting, choosing not to do HH, and the telephone) E‐learning materials including videos modelling knowledge, guided practice and promotion of active learning 10 posters (multiple copies, new one each month) Prize for photo competition NH certificate of good HH Small bottle of hand sanitiser for lesson participants See website (www.zorgvoorbeter.nl/hygiene/handhygiene-verbeteren-verpleeghuis) for materials (in Dutch) used for intervention:[25]‐ Manual (84p)‐ E‐learning module‐ PowerPoint presentation and script‐ Assignments‐ Awareness activities‐ Audit materials‐ Policy materials‐ Posters Adherence recording application and computer table Adherence observer training materials using method adapted from a study in Dutch hospital[26]: videos and case studies and examination using videos from Hand Hygiene Australia[27][1] World Health Organization. (‎2012)‎. Hand hygiene in outpatient and home‐based care and long‐term care facilities: a guide to the application of the WHO multimodal hand hygiene improvement strategy and the “My Five Moments For Hand Hygiene” approach. World Health Organization. apps.who.int/iris/handle/10665/78060 (accessed 15 June 2022)[2] Moment 1 (before touching a resident) = Room In; Moment 4 (after touching a resident) and Moment 5 (after touching a resident’s surroundings) = Room Out; Moment 2 (before a clean/antiseptic procedure) = Before Clean; Moment 3 (after body fluid exposure risk) – After Dirty[3] Handsome: handhygiëne in verpleeghuizen.: Zorg voor beter; 2019 May 03. URL: www.zorgvoorbeter.nl/handsome (accessed 7 June 2022)[4] Veiligheid en Kwaliteit: Project Handen uit de Mouwen.: Stichting Samenwerkende Rijnmond Ziekenhuizen[5] Auditor training.: Hand Hygiene Australia URL: www.hha.org.au/audits/auditor-training (accessed 7 June 2022)See Table 1 of Teesing 2020a and Teesing 2020b for more details 1. Policy change:‐ management meeting (with senior nursing home manager, infection prevention specialist, and facilities manager),‐ personal hygiene rules ‐ HH materials audit 2. Nursing staff interventions (The New Way of Working)i) 3 live lessons:a. introduction of HANDSOME/WHO HH moments; teaching and discussion re HH when handling medication, food, laundry; when to use hand sanitiser/soap/gloves. Team HH goal‐setting;b. make inventory and solutions for barriers to HH adherence; andc. exercise washing hands with paint to see where missed; teaching how to disinfect handsii) e‐learning: introduction and 7 lessons showing:‐ correct/incorrect HH behaviour‐ common HH actions‐ when to use gloves‐ food and medication preparationQuizzes:iii) reminder posters hung throughout NH showing large picture of hands and text: “Did you remember to wash your hands?” (in Dutch’)iv) photo competition: prize for best photo of hands 3. Arts and craft project for residents involving hands that NH displays Adherence recording procedures Provision of hand sanitiser to lesson participants Provision of good HH certificate to NH if higher than average adherence Provision of nurse’s watch on completion of e‐learning Provision of adherence observers trainingMeeting and materials provided by researcher Study team member delivered 3 live lessons with involvement of senior NH manager Senior NH managers involved in delivery of aspects, including a lesson on NH personal hygiene policy between lessons 1 and 2 Nurses and doctors in training provided adherence observation and assessmentFace to face in groups (management and nursing staff) Lessons in groups of maximums of 18/session Online individual e‐learningIn residents’ rooms or other areas of 2 units each of 33 Dutch nursing homes with ≥ 3 nurses providing intense psychogeriatric and/ or somatic care to geriatric residents Meetings on‐site Lessons on‐site and online Posters throughout NH4 months (Jan to Apr 2017) Management meeting (45 to 60 min) Personal hygiene policy presentation (10 min) Live lessons:1 (20 min)2 (30 min)3 (40 min) given multiple times on 1 day E‐learning: 5 to 10 min each Adherence observer training: 2 to 3 days Adherence observation: during observation hours (8 am to 1.30 pm, weekdays)Persuasive communication used to encourage continuing when NH wanted to stop When < 3 nurses working at the unit, either the observers continued observations at an additional ward (who also received the intervention) or they stopped observing HH needed to happen in the same room as action occurred, except if a nurse brought a resident to another room, they carried something soiled or no door needed to be opened before leaving the room; for these instances, HH should take place at the end of actionNone described, except that the process was iterative in response to feedback from individual nursing homesUnobtrusive HH direct observation disguised as registering of frequency of health care activities recorded on computer tablet (see Figure 2 in Teesing 2020a and Table 3 of Teesing 2020b) Compliance registered if HH occurred immediately before (moments 1 and 2) or after (moments 3, 4 and 5) a HH opportunity without touching another object (e.g. door handle) and only if hand sanitiser or soap, water and paper towel used Hand‐related personal hygiene[28] for each nurse according to Dutch guidelines[29]1 / every nurse / day Attendance at live lessons and e‐learning was recorded Participants asked if HH policy information received and if posters seen HH compliance (12 m f/u)IG: 36%CG: 21%(OR 2.28, CI 1.67 to 3.11) HH compliance increased more for IG than CG for each WHO‐defined moment, except for moment 2 Estimated attendance at lessons:varied per unit: 23% had < 50% attending at least 1 lesson, 18% had 50% to 74% attendance at at least 1 lesson and 59% had > 75% attendance at least 1 lesson (n = 22).
Temime 2018Multifaceted hand hygiene programme (including alcohol‐based hand rub)Nursing home staff, residents, visitors, and outside care providersNursing homes and their residents, staff, and visitors and external providers have an increased risk of person‐to‐person transmission of pathogens, and HH is a simple and cost‐effective tool for infection control; however, compliance with HH is poor in nursing homes.Dispensers and pocket‐sized containers of hand rub solution Posters promoting hand hygiene Developed local HH guidelines eLearning module on infection control and HH training with online quizzes requiring sufficient performanceFacilitated access to hand rub solution Campaign to promote HH with posters and event organisation Formation of local work groups in each NH Development of local HH guidelines Staff education using eLearning Monitoring of quantity of hand rub solution usedSame nurse provided HH training for all NHs. Provision of hand rub by NH Local work group developed guideline. eLearning module and posters presumably developed by research team.Provision of materials face‐to‐face Education and quizzes via eLearningNursing homes in France1 year overall One‐off provision of hand rub One‐off eLearning repeated if unsatisfactory performance.If staff did not score sufficiently on online quiz, they were invited to repeat the eLearning.  None described.Estimated mean amount of hand rub solution used per resident per day assessed as proxy for HH frequency, based on quantity of hand rub solution bought by NH (which was routinely monitored in all the NHs).Hand rub solution used:baseline quantity of consumed hand rub solution was 4.5 mL per resident per day.Over the 1 year, mean quantity consumed was significantly higher in intervention NH (7.9 mL per resident per day) than control (5.7 per resident per day).
Turner 2004aClinical trial 1 3 active interventions (no control) Product:A. Ethanol
B. Salicylic acid
C. Salicylic acid with pyroglutamic acid Healthy volunteersAssess the residual virucidal activity of organic acids used in currently available over‐the‐counter skin products for the prevention of experimental rhinovirus colds1.7 mL of hand products:A. 62% ethanol, 1% ammonium lauryl sulphate, and 1% Klucel)B. 3.5% salicylic acid, or vehicle containingC. 1% salicylic acid and3.5% pyroglutamic acidDisinfection of hands then application of test product then allowed to dry.15 min later, fingertips of each hand contaminated with 155 TCID50of rhinovirus type 39 in a volume of 100 μL.Hands air‐dried for 10 min.Intentional attempted inoculation with virus by contact with fingers, conjunctiva, and nasal mucosa with fingers of right hand.Left hand eluted in 2 mL of virus‐collecting broth.ResearchersFace‐to‐face individuallyCommunities in Manitoba, Canada1.7 mL of product applied. See What for timingNot describedNot describedNot describedNot described
Turner 2004bClinical trial 22 active interventions (no control) Skin cleaner wipe product:
 A. Pyroglutamic acidB. EthanolHealthy volunteersAssess the residual virucidal activity of organic acids used in currently available over‐the‐counter skin products for the prevention of experimental rhinovirus coldsSkin cleanser wipe containing:A. 4% pyroglutamic acid formulated with 0.1% benzalkonium chlorideB. 62% ethanol Application of product to hands with towelette then allowed to dry.15 min later, fingertips of each hand contaminated with 106 TCID50of rhinovirus type 39 in a volume of 100 μL.Intentional attempted inoculation with virus by contact with fingers, conjunctiva, and nasal mucosa with fingers of right hand.Left hand eluted in 2 mL of virus‐collecting broth.ResearchersFace‐to‐face individuallyCommunities in Manitoba, CanadaDose not reported; see What for timing Additional group challenged 1 h after application; final group challenged 3 h after application (remained at study site and not allowed to use or wash hands between). Not describedNot describedNot describedNot described
Turner 2012Antiviral hand lotionHealthy adultsReduce rhinovirus infection and illness through hand disinfection with ethanol and organic acid sanitiserLotion containing 62% ethanol, 2% citric acid, and 2% malic acid Daily diaryProvision of lotion and instructions for use Meetings with participants to check compliance  Staff of study site presumably supplied lotion. Study site staff met with participants.Face‐to‐face and presumably individually, but not specifiedStudy site at university community in the USA9 weeks Every 3 hours whilst awakeand after hand‐washing for 9 weeks Compliance meetings twice weekly for first 5 weeks then weekly meetings with participantsNone reported.None reported.Self‐reported daily diary of time of each product application Twice weekly for 5 weeks then weekly meetings with participants to reinforce compliance with treatment“All subjects … applied at least 90% of the expected amount of hand treatment” (p. 1424)
Yeung 2011Multifaceted hand hygiene programme (including alcohol‐based hand rub)Long‐term care facilities and their healthcare workersPromote use of alcohol‐based hand rub by staff in LTCFs as an effective, timely, and low‐irritant method of hand hygiene in a high‐risk environmentFree supply of pocket‐sized containers of alcohol‐based antiseptic hand rub (either WHO formulation I (80% ethanol) or II (80% propanol) carried by each HCW (supplier: Vickmans Laboratories) Replacement hand rub as required Hand hygiene seminar content Reminder materials (3 to 5 posters and specially designed ballpoint pens)Provision of materials Provision of hand hygiene seminars to HCWs covering:indications, proper method, and importance of antiseptic hand rubbing and washing according to WHO 2006a) guidelines Provision of feedback session Direct, unobtrusive observation of hand hygiene adherence Training of observation staff  Study team delivered the materials, seminars, and observer training. Administrative staff of LTCF provided replacement hand rub and communicated with HCWs. 6 registered nurses conducted direct observation of adherence after 2‐hour training (100% interrater reliability).Delivered face‐to‐face and individually for hand rub and pens; not described if education was individually or by group, but seminar implies as a groupLTCFs in Hong Kong Posters posted in common areas. Adherence observations occurred in common rooms and resident rooms but not bathing or toilet areas.7 months overall Initial 2‐week intervention period, then 7 months of hand rub provision and reminders 3 identical seminars at start of intervention; each staff member to attend once Feedback session 3 months after start of intervention 2‐hour training of observers Adherence observations either 9 am to 12 pm or 3 pm to 6 pm, 1 LTCF at a timeReplacement of hand rub as requiredAs adherence dropped off in the middle months, the feedback session was delivered.Direct observation of HCW adherence to hand‐washing and antiseptic hand rubbing (recorded separately and anonymously) during bedside procedures or physical contact with residents 3300 hand hygiene opportunities during 248.5 hours of observation on 92 days90% attendance of seminars Hand rubbing with gel increased significantly from 1.5% to 15.9%. Hand‐washing decreased significantly from 24.3% to 17.4%.Control: 30% Overall hand‐washing adherence increased from 25.8% to 33.3%.
Zomer 2015Hand hygiene products and training  Daycare centres and their caregivers (staff)Reduce infections in children attending DCCs through improved access to HH materials (Zomer 2013a) and compliance of their DCC caregivers to hand hygiene guidelines based on socio‐cognitive and environmental determinants of caregivers’ HH behaviour[30] (Zomer 2013b)HH products:dispensers for paper towels, soap, alcohol‐based hand sanitiser, and hand cream, with refills for 6 months Reminder posters and stickers for children and DCC caregivers Training materials including bookletProvision of free HH products sponsored by SCA Hygiene Products, Sweden. Provision of posters and stickers for children and staff Provision of training about RIVM 2011 for mandatory HH[31] Distribution of training booklet Team training sessions aimed at goal‐setting and formulating HH improvement activities (Erasmus 2011; Huis 2013)Study team arranged supply of HH products and presumably provided training.Products provided to DCCs in person for staff use. Mode of training not specified. DCCs in regions of the Netherlands6 months overall Initial one‐off supply of products 3 training sessions with 1‐month interval 2 team training sessionsReplacement hand hygiene provided as required.None described.6‐month follow‐up observation of whether intervention dispensers and posters/stickers in use Survey of DCC caregivers HH guidelines compliance observed at 1, 3, and 6 months' follow‐up:no. of HH actions/no. of opportunities  2 DCCs did not use any HH products. Sanitiser products used in at least 1 of 2 groups in 94%, 89%, 86%, and 45% of intervention DCCs. Posters used in 86%, stickers in 74%. DCC survey results:79% attended at least 1 training session; 77% received HH guidelines booklet. HH compliance at 6 months:IG: 59% vs CG: 44% (Zomer TP, et al, unpublished data) All intervention DCCs received guidelines training; all but 2 received at least 1 team training.
Hand hygiene and masks
Aelami 2015Hygienic education and packageReligious pilgrimsPrevent influenza‐like illness by reduced infection transmission through personal hygiene measuresHygiene package of:alcohol‐based hand rub (gel or spray)surgical maskssoappaper handkerchiefsuser instructionsNot clearly described, but it appears that packages may have been distributed by trained physicians before departure to or on site of country of pilgrimageNot specifically describedNot described, but it appears that packages were distributed face‐to‐face and individuallyNot described if before departure (from Iran) or on site (in Saudi Arabia)One‐off during Hajj seasonNot describedNot describedNot describedNone described
Aiello 2010 2 active interventions: A. Face mask (FM)B. Face mask and hand hygiene (FM + HH)Students living in university residencesReduce the incidence of and mitigate ILI by use of non‐pharmaceutical interventions of personal protection measures7 face masks (standard medical procedure masks with ear loops TECNOL procedure masks; Kimberly‐Clark)7 re‐sealable plastic bags for mask storage when not in use (e.g. eating) and for disposal Alcohol‐based hand sanitiser(62% ethyl alcohol in a gel base, portable 2‐ounce squeeze bottle, 8‐ounce pump) Hand hygiene education (proper hand hygiene practices and cough etiquette) via emailed video, study website, written materials detailing appropriate hand sanitiser and mask useWeekly supply of masks through student mailboxes Provision of basic hand hygiene education through an email video link, the study website, and written materials; instruction to wear mask as much as possible; education in correct mask use, change of masks daily, use of provided re‐sealable bags for mask storage and disposal Provision of replacement supplies which students signed for upon receiptNot described, except education provided via study website (URL not provided) “Trained staff” for compliance monitoring Study‐affiliated residence hall staff provided replacement supplies.Education via email and study website; provision of masks and sanitiser in person to residencesUniversity residence halls in the USAOne‐off education, 6 weeks (excluding spring break) of face mask and/or hand hygiene measures which commenced at “the beginning of the influenza season just after identification of the first case of influenza on campus” (p.496). Replacement supplies provided as needed.Mask wearing during sleep optional and encouraged outside of residence.  University spring break occurred during weeks 4 and 5 of the study, with most students leaving campus and travelling; they were not required to continue protective measures at that time.Weekly web‐based student survey included: self‐reported average number of times hands washed/day and average duration of hand‐washing to obtain composite "optimal handwashing” score (at least 20 s ≥ 5/day);average no. of mask hours/day/week; average hand sanitiser use/day/week and amount used. Trained staff in residence hall common areas observed silently and anonymously improper mask use, instances of hand sanitiser use.Average mask use hours/day:FM + HH 2.99 versus FM 3.92 Average hand‐washing times/day:FM + HH 6.11 versus FM 8.18 vs control group 8.75 Daily washing seconds/day:FM + HH 20.65 versus FM 23.15 vs control 22.35 Hand sanitiser use times/day:FM + HH: 5.2 versus FM 2.31 vs control 2.02 No. of proper mask wearing participants/hour of observation:FM + HH 2.26 versusFM 1.94
Aiello 20122 interventions: A. Face mask (FM)
B. Face mask and hand sanitiser (FM + HH)Students living in university residencesPrevent ILI and laboratory‐confirmed influenza by use of non‐pharmaceutical interventions of personal protection measures (e.g. face masks and hand hygiene)Packets of 7 standard medical procedure masks with ear loops (TECNOL procedure masks, Kimberly‐Clark, Roswell, GA, USA) and plastic bags for storage during interruptions in mask use (e.g. whilst eating, sleeping) and for daily disposal Hand sanitiser (2‐ounce squeeze bottle, 8‐ounce pump bottle with 62% ethyl alcohol in a gel base) Replacement face masks and hand sanitiser Educational video: proper hand hygiene and use of standard medical procedure face masksIntervention materials and educational video provided. Supply of masks and instructions on wearing Provision of replacement masks or sanitisers as needed on siteTrained study staff available at tables in each residence hall for surplus masks and sanitiser and for observing complianceHygiene packs delivered to student mailboxes; face‐to‐face supply also availableUniversity residence halls in the USAOne‐off educational video at start Weekly supply of hygiene packs Masks to be worn at least 6 hours/day Study staff available onsite with replacement supplies as needed for duration of intervention (6 weeks, excluding spring break)Students encouraged but not obliged to wear masks outside of residence hall.1‐week university spring break during the study when majority of students left campusWeekly student survey including compliance (e.g. masks hours/day, frequency and amount of sanitiser use, number of hand washes/day, duration of hand‐washing (seconds) Observed compliance completed by trained study staff who daily and anonymously observed mask wearing in public areas of residences.Self‐reported mask wearing: no significant difference Sanitiser use:significantly more in FM + HH than FM or control groups More results in S1 of paper. Staff observed an average of 0.0007 participants properly wearing a mask for each hour of observation.
Cowling 2009 2 active interventions in addition to control of lifestyle education:
 A. Enhanced hand hygiene (HH)
 B. Face masks and enhanced hygiene (FM + HH) Householders with index patient with influenzaReduce transmission of influenza in households through personal protective measuresA. and B.Liquid soap for each kitchen and bathroom: 221 mL Ivory liquid hand soap (Proctor & Gamble, Cincinnati, OH, USA) Alcohol hand rub in individual small bottles (100 mL) WHO recommended formulation I, 80% ethanol, 1.45% glycerol, and 0.125% hydrogen peroxide (Vickmans Laboratories, Hong Kong, China) B. Adults: box of 50 surgical face masks (Tecnol–The Lite One (Kimberly‐Clark, Roswell, GA, USA) to each household member or C. Children 3 to 7: box of 75 paediatric masks    Home visits Provision of soap, hand rub, and masks as applicable and when to use them HH: education about efficacy of hand hygiene Demonstration of proper hand‐washing and antisepsis techniques + FM: education about efficacy of surgical face masks in reducing disease spread to household contacts if all parties wear masks Demonstration of proper wearing and hygienic disposal All groups: provision of education about the importance of a healthy diet and lifestyle, both in terms of illness prevention (for household contacts) and symptom alleviation (for the index case) Trained study nurse provided interventions.Face‐to‐face to householdersHouseholds in Hong KongInitial home visit scheduled within 2 days (ideally 12 h) of index case identification. Further home visits day 3 and 6, 7‐day follow‐up HH: use of liquid soap after every washroom visit, sneezing or coughing, when their hands were soiled. Use rub when first returning home and immediately after touching any potentially contaminated surfaces FM: masks worn as often as possible at home (except eating or sleeping) and when the index patient was with the household members outside of the householdNot describedNot describedMonitoring of adherence during home visits Evaluation of adherence on final visit by interview or self‐reported practices and counting of amount of soap and rub left in bottles and remaining masks for FM groupMost initial visits completed within 12 h. Intervention groups “reportedhigher adherence … than thecontrol group. Self‐reported data were consistent with measurements of amount of soap, alcohol hand rub,and face masks used” (p.443) (see Table 6 in paper).“Adherence to the hand hygiene intervention wasslightly higher in the hand hygiene group than the face maskplus hand hygiene group.” Median masks used:Index: 9Contact: 4 More details in paper and Appendices
Larson 2010 2 active interventions in addition to control of URI education: A. Alcohol‐based hand sanitiser (HS) B. Face masks and hand sanitiser (FM + HS)Hispanic householders with at least 1 preschool or elementary school childReduce incidence and secondary transmission of URIs and influenza through non‐pharmaceutical household level interventionsA. and B.2‐month supply of hand sanitiser in 8‐, 4‐, and 1‐ounce containers:PURELL (Johnson & Johnson, MorrisPlains, NJ, USA) B. 2‐month supply of masks:ProcedureFace Masks for adults and children (Kimberly‐Clark, Roswell, GA, USA) Replacement supplies at least once every 2 months Disposable thermometers Educational materials about URI prevention, treatment, and vaccination (written in Spanish or English language)Provision of materials and instructions for when to use including demonstration of use and observation of return demonstration by householder A. Mask worn when householder had: “temperature of ≥37.8°C and cough and/or sore throat in the absence of a known cause other than influenza” (CDC definition of influenza‐like illness at the time). Home visits to reinforce adherence, replenish supplies and record use, answer questions B. Telephone calls to reinforce mask use All groups received URI educational materials.4 trained bilingual research assistants (RAs) with minimum baccalaureate degree and experience in community‐based research; procedures were practised with each other until demonstrated proficiency  Face‐to‐face to householdersHouseholds in New York, USA19‐month follow‐up Initial home visit, then at least every 2 months Sanitiser for use at home, work, and school B. Telephone calls days 1, 3, 6 Masks worn for 7 days when within 3 feet of person with ILL or no symptoms.  Change masks between interactions with person with ILL Householders' questions and misconceptions addressed on home visits.  None described.RA home visits for adherence with random accompaniment by project manager, who also made random calls to householders Telephone calls to reinforce mask use Used bottles or face masks, or both, monitored for usage.Sanitiser use (mean ounces/month)HH: 12.1FM + HH: 11.6 Mask compliance was “poor”: 22/44 (50%) used within 48 hours of onset.Mask users reported mean mask use of 2. 
Simmerman 20112 active interventions: A. Hand‐washing education and hand‐washing kit (HW) B. Hand‐washing education, hand‐washing kit, and face masks (HW + FM)Households with a febrile, influenza‐positive childDecrease influenza virus transmission in household with a febrile influenza‐positive child through promoted use of hand‐washing or hand‐washing with face mask useA. and B.Hand‐washing kit per household including graduated dispenser with standard unscented liquid hand soap (Teepol brand. Active ingredients: linear alkyl benzene sulfonate, potassium salt, and sodium lauryl ether sulphate) Replacement soap as needed Written materials from education including pamphlets and posters attached near sinks in household. B. Box of 50 standard paper surgical face masks and 20 paediatricface masks (Med‐con company, Thailand #14IN‐20AMB‐30IN)A. and B.Provision of intensive hand‐washing education on initial home visit to household members with 5 approaches: discussion, individual hand‐washing training, self‐monitoring diary, provision of soap, and provision of written materials (Kaewchana 2012) Individual hand‐washing training ("why to wash", "when to wash", and "how to wash" in 7 hand‐washing steps described in Thailand Ministry of Public Health guidelines) B. Provision of education of benefits of and appropriate face mask wearing Soap replaced as needed. More details (Kaewchana 2012)Study nurse conducted home visits, provided education and monitoring activities.Education provided face‐to‐face as a group to household member and individually for hand‐washing training.In homes (in Bangkok, Thailand)One‐off provision of kits at initial home visit conducted within 24 hours of enrolment Subsequent home visits on days 3, 7, and 21 90‐day supply of hand‐washing supplies 30‐minute education provided at initial home visitB. No face masks whilst eating or sleeping as impractical and could hinder breathing in ill child Impromptu education and training provided by nurses as questions arose.  None described.Self‐monitoring diary recording hand‐washing frequency > 20 s and face mask use for that group Reinforcement of messages by nurses on subsequent home visits Amount of household liquid soap and number of face masks used Reported average hand‐washing episodes/day:HW: 4.7HW + FM: 4.9Parents had highest frequency (5.7), others (4.8), siblings (4.3), index cases (4.1). Average soap used/week:HW: 54 mL/personHW + FM: 58.1 mL/person B. Mask use:12/person/weekMask wearing median minutes/day: 211Parents 153,other relations59, index patients 35, siblings 17
Suess 20122 active interventions in addition to written information: A. Mask/hygiene (MH) B. Mask (M) Households with an influenza‐positive index case in the absence offurther respiratory illness within the preceding 14 daysPrevent influenza transmission inhouseholds through easily applicable and accessible non‐pharmaceutical interventionssuch as face masks or hand hygiene measures A. Alcohol‐based hand rub (Sterilium, Bode Chemie, Germany) A. and B.Surgical face masks in 2 different sizes:children < 14 years (Child’s Face Mask, Kimberly‐Clark, USA) and adults (Aérokyn Masques, LCH Medical Products, France) Written information provided on correct use of intervention and on infection prevention (Suess 2011) (tips and information on the new flu A/H1N1)(URL provided is no longer active) Digital tympanic thermometer General written information on infection prevention A. Provision of hand rub and masks A. and B. Provision of masks only Provision of thermometer and how to use it Mask fit assessed (at first household visit) Information provided by telephone and written instructions at home visit on proper use of interventions and recommendations to sleep in a different room than the index patient, not to take meals with the index patient, etc. (Suess 2011) In‐person demonstration of interventions at first home visit All participating households received general written information on infection prevention.Study personnel arranged provision of materials, rang the participants, visited the homes, demonstrated and assessed fit of masks.  Provision of materials in person to households Initial telephone delivery of information Face‐to‐face home visitsHouseholds in Berlin, GermanyOver 2 consecutive flu seasons Day 1 households received all necessary material instructions. Household visits no later than 2 days after symptom onset of the index case, then days 2, 3, 4, 6, 8 (5 times) or on days 3, 4, 6, 8 (4 times) depending on the day of recruitment Hand rub use: after direct contactwith the index patient (or other symptomatic householdmembers), after at‐risk activities or contact[31] Mask use: at all times when index patient and/or any other household member with respiratory symptoms were together in 1 room Regular change of face masks, not worn during the night or outside the householdAdult masks worn ifmasks for under 14‐year‐oldsdid not fit properly. If other household members developed fever (> 38.0 °C), cough, or sore throat, they were asked to adopt the same preventive behaviour as the index patient.In the season 2010/11 participants also recorded number of masks used per day.Self‐reported daily adherence with face masks, i.e. if they wore masks “always”, “mostly”, “sometimes”, or “never” as instructed.Participants of the MH households additionally noted the number of hand disinfections per day. Exit questionnaire about (preventive) behaviour during the past 8 days, general attitudes towards NPI, the actual amount of used intervention materials, and, if applicable, problems with wearingface masks. Used intervention material per household member was calculated by dividing the amount used per household by the number of household members. See paper and Suess 2011 for more details.Face mask use (median/individual):MH: 12.6M: 12.9 Daily adherence was good, reaching a plateau of over 50% in nearly all groups from the third day on. MH hand rub use (median):87 mL (Suess 2011) MH mean frequency of daily hand disinfection: 7.6 (SD 6.4) times per day See paper and Suess 2011 for more results.
Hand hygiene and surface/object disinfection
Ban 2015 Hand hygiene and surface cleaning or disinfectionKindergartens and the families of their studentsReduce transmission of infection in young children from contaminated surfaces or hands through hand hygiene and surface cleaning or disinfectionAntibacterial products for hand hygiene and surface cleaning or disinfection:liquid antimicrobial soap for hand‐washing (0.2% to 0.3% parachlorometaxylenol).Instant hand sanitiser for hand disinfecting (72% to 75% ethanol), antiseptic germicide (4.5% to 5.5% parachlorometaxylenol, diluting before use).Bleach (4.5% to 5.0% sodium hypochlorite, diluting before use) for surface disinfecting.Produced by Whealthfields Lohmann (Guangzhou) Company Ltd.Provision of products to kindergartens and families Instruction of parents or guardians and teachers in hand hygiene techniques and use of antibacterial products Daily cleaning of kindergartens with products At least twice/week cleaning of homes and weekly cleaning or disinfecting of items such as children’s toys, house furnishings, frequently touched objects (doorknobs, tables or desks), kitchen surfaces (utensils, cutlery, countertops, chopping boards, sinks, floors, etc.), bathroom surfaces (toilet, sink, floor, etc.) Monitoring activitiesResearch team provided products and instructions and monitoring.  Materials provided to kindergartens and families in person and presumably instructions in person to families and staff.  In kindergartens (hard surfaces) and families’ homes (Xiantao, China)1 year overall Daily hand‐washing with soap before eating, after using bathroom, nose blowing, and outdoor activities Hand sanitiser carried daily. Kindergarten cleaning daily Home cleaning at least twice/weekFamilies and teachers could contact study management at any time as needed. Exchange of empty bottles for new ones at any timeNot describedClose contact with teachers and families for monitoring, e.g. unscheduled parents’ meetings, quarterly home visits, phone interviews, and monthly cell phone messages Monthly survey of consumption of products by volume, total usage, person usageConsumption of products by person (mL/person/day).Liquid soap: 7.7Sanitiser: 1.4Bleach: 25.0Antiseptic‐germicide: 12.5  
Carabin 1999Hygiene programmeDaycare centres and their staff and childrenReduce infections in at‐risk children (under 3 years old) in DCCs with inexpensive, easily implementable and practical interventionsHygiene materials and documents, e.g. colouring books, hand‐washing posters, hygiene videotapes Materials for training Reimbursement of equivalent of 1 full‐time educator’s salary Bleach (diluted 1:10) for toy and play area cleaningProvision of comprehensive hygiene training session to entire DCC staff, especially the educators of participating classrooms Training in recommendations for hygiene practices:i. toy cleaningii. hand‐washing technique and scheduleiii. use of creative reminder cues for hand‐washingiv. open window for daily periodv. sandbox and play area cleaning Payment of salary of educator for the day to encourage participation DCC meetings to discuss training session with all staffTraining appears to have been provided by study team.Appears staff trained as a group, i.e. “entire DCC staff”  Daycare centres in Canada Location of training not described, except may have been off‐site from DCCs since 1 DCC did not “send” staff to training.15‐month trial One‐off 1‐day training Toy cleaning at least every 2 days Hand‐washing at least after DCC arrival, after outside play, after bathroom, before lunch Open windows at least 30 min/day Biweekly cleaning of sandbox/play areaTeachers to use creative reminder cues for hand‐washing with childrenNot describedFollow‐up telephone questionnaire for DCC directors about following training recommendationsUse of materials: colouring book: 22/24poster: 23/24videotapes: 18/24staff meetings: 19/24 Increased frequency of toy cleaning: 6/24Use of rake and shovel for sandpit: 17/24Frequency of cleaning sandbox: 14/24  
Kotch 1994 HygieneCaregivers at child daycare centres (CDCCs)Develop feasible, multi component hygienic intervention to reduce infections in children at CDCCs who are at increased riskHygiene curriculum for caregivers Availability of soap, running water, and disposable towels Waterless disinfectant scrub (Cal Stat) used only if alternative was not washing at all. Handouts posted in CDCC. Delivery of hygiene curriculum to caregivers through initial training session which required demonstration of participants’ hand‐washing and diapering skills Local procedures:Hand‐washing of children and staffDisinfection of toilet and diapering areasPhysical separation of diapering areas from food preparation and serving areasHygienic diaper disposalDaily washing and disinfection of toys, sinks, kitchen and bathroom floorsDaily laundering of blankets, sheets, dress‐up clothesHygienic preparation, serving, and clean up of food Separate training of food handlers As‐required induction training for new staff Onsite follow‐up training reinforcing adaptations, demonstrations and discussion of hygiene techniques, responding to questions, and review of handouts Monthly meeting with centre directors to encourage leadership and supportResearch team delivered training. Scrub donated by Calgon Vetal Laboratories.Face‐to‐face training and follow‐up group and individuallyClassrooms of child daycare centres in the USA8 months overall 3‐hour initial training session Cleaning schedules as described in column What (procedures) Onsite follow‐up training 1 week and 5 weeks later Follow‐up sessions addressed questions and local adaptations to procedures. As‐required induction training  During intervention, research team encouraged directors to address physical barrier to hygiene practice, such as distance between sink and diapering areas and sink access in rooms.Follow‐up sessions reinforced training. Meeting with directors 5 weekly unobtrusive recorded observation by training staffRate of compliance to barrier modification was better in younger centres, which were more likely to have written guidelines.
McConeghy 2017 Multifaceted hand‐washing and surface‐cleaning interventionNursing homes and their staffReduce exposure to pathogensand person‐person transmission in high‐risk facility of close environment and potentially contaminated surfaces through multifaceted intervention equipping staff to protect residents from infection within the “culture” of careEducation and launch materials Online module for certified nursing assistants about: infection prevention, product, and monitoring "Essential bundle" of hygiene products supplied at no cost:‐ hand sanitiser gel and foam‐ antiviral facial tissues‐ disinfecting spray‐ hand and face wipesPlus additional:‐ 4 skin cream and wipe products iPads for compliance audits Newsletters for support during intervention  Pre‐intervention:NH administrators required to:‐ identify a "Heroes In Prevention" champion and team‐ allow all staff participation in education‐ iPad use for staff in each floor or community‐ ask staff to incorporate intervention into workflow Delivery of 3 components:‐ education‐ cleaning products‐ compliance audit and feedback Education:Launch event for all staff to publicise programme and explain rolesIntensive training of "hygiene monitors" for data collection and compliance audit and feedback toolTraining of site championTraining of select group of certified nursing assistants (online module) Audit and feedback activities Ongoing support during intervention:‐ newsletter with best practices‐ teleconferences with each NH‐ "onboarding" education of new staffStudy personnel equipped staff with knowledge and tools and support. NH staff (e.g. champion, hygiene monitors, nursing assistants) delivered aspects of interventions after specific training.Face‐to‐face interaction with staff for planning and some aspects and delivery of products Some aspects delivered online (e.g. nursing modules, compliance auditing)Nursing homes in the USA Onsite and at unit/team levels Online training6 months overall: training period: 3 months 1‐hour launch event 1 or 2 hygiene monitors/site 1 champion/site 1‐hour online module for selected nursing assistants iPads for each community or floor Weekly teleconferencesinitially decreased in frequency over time. Weekly measurement of product consumptionSites could use existing comparable products from another vendor and fill in any gaps with study products. New staff provided with education, as needed and came onboard. Retraining of sites with low training participation rates2 sites retrained due to low training participation rate.Cloud‐based audit and feedback system via secure login to web browsers on NHs’ existing computers or via iPads included weekly product consumption to get measure:weekly count of product units consumed x no. of hand hygiene occasionsOnline training participation rates:> 90% for 3/5 sites,13% and 23% for 2/5 Administrators demonstrated high fidelity in reporting measures ofhand‐washing (> 80% of time). Hand‐washing rates in Figure 1B in paper reported as “relatively constant” and “not ideal in the first few months”, but improved significantly over time.  
Sandora 2008 Multifactorial intervention, including alcohol‐based hand sanitiser and surface disinfectionElementary school and its studentsReduce transmission of infections in schoolchildren through improved hand hygiene and environmental disinfection1 container of disinfecting wipes (Clorox Disinfecting Wipes (The Clorox Company, Oakland, CA, USA); active ingredient, 0.29% quaternary ammonium chloride compound) Pre‐labeled 1.7‐ounce containers of alcohol‐based hand sanitiser (AeroFirst non‐aerosol alcohol‐based foaming hand sanitiser (DEB SBS Inc, Stanley, NC, USA, for The Clorox Company); active ingredient, 70% ethyl alcohol) Receptacle in classrooms for empty containersSanitiser and wipes provided to classroom/teacher with instructions for use. Teachers disinfected desks once daily. Hand sanitiser to be used:before and after lunch, after use of the restroom (on return to the classroom; hand hygiene with soap and water occurred in the restroom, because sanitisers were not placed there), after any contact with potentially infectious secretions (e.g. after exposure to other ill children or shared toys that had been mouthed)Research team arranged supply of materials and instructed teachers on use. Teachers instructed in use of materials and in collecting empty containers and distributing new product.Products provided to schools. Instruction provided face‐to‐face to teachers and children.Elementary schools and their classrooms in the USA8‐week period Desks disinfected once a day.  Products replenished as needed.None described.Individually labelled containers collected every 3 weeks from the classroom to assess adherence.  Product usage: average wipes used/week: 897 (128 wipes/classroom/week) Average bottles of hand sanitiser used per week: 8.75 (1.25 bottles/classroom/week)
Quarantine/Physical distancing
Helsingen 2021Rapid‐Cycle Re‐Implementation of TRAining Facilities in Norway (TRAiN) hygiene and physical distancing measuresMembers of health and fitness training facilities aged 18 to 64 years not atincreased risk for severe COVID‐19Enable safe re‐opening of fitness training facilities to maintain health and fitness by reducing the risk of SARS‐CoV2 transmissionInfection mitigation measures described by “Norwegian guidelines for Hygiene and Social Distancing in Training Facilities during the COVID‐19 Pandemic” (in Norwegian t-i.no/wp-content/uploads/2020/04/Bransjestandard-for-sentre.pdf) See Supplementary Appendix for “Standard for COVID‐19 infection prevention measures in fitness centers during the TRAiN‐study” Disinfectant readily available at workstations and strategic places (reception, booking station, changing rooms, toilets, water taps used for drinking or refilling bottles) Rubbish cans without lids Washbasin with soap or hand disinfection Personal microphones for instructors (i.e. not shared) Infection preventive measures reminders online and via posters in facilitiesImplementation of the following during regular floor training facilities and group classes:‐ avoidance of body contact‐ 1 metre distance between individuals,‐ 2 metre distance for high intensity activities Provision of disinfectants at all workstations Requirement of HW and cleaning of all equipment by members before and after use with utensils provided No physical contact between participants or participants and instructors Regular cleaning of facilities by facility employees Create lists of what should be cleaned and how often Disinfection of instructor microphones Extra cleaning of frequently touched surfaces (e.g. door handles, card readers, washbasin batteries) Frequent refilling at all hygiene stations Avoid queuing by making sure group classes do not start and stop at same time and keep 15 min minimum between group classes Access control by facility employees Closure of showers and sauna but changing rooms open Staff presence during all opening hours Removal of lids on trash cans Reminders of infection preventive measures Communication to members about changes to training for social distancing Advice to members to stay home if any COVID‐19 related symptoms Advice to members to avoid touching eyes, nose and mouth Closure of childcare facilitiesFacility employees controlled access and enforced implementation of guidelines and procedures at all times Staff present during all opening hours Not reported if training needed for facility staffFace‐to‐face individually and as a group5 health and fitness training facilities in Oslo, Norway3 weeks May 22nd to June 15th, 2020 Hours of access not reported;presumably the participants had unlimited access to training facility within the procedures for distancingMasks not required, so were optional Change rooms available Access controlled to avoid overcrowding Staff monitored that distance measures were ensured Number of people attending depended on size of gym and associated changing rooms, showers and toilets. Facility to calculate the maximum number who could train at the same time while maintaining 1 to 2 m distance, as well as toilet, shower and change room capacityNone describedStaff monitored access and distancing No apparent measures of fidelityNone described
Miyaki 2011Quarantine from work (stay‐at‐home order)EmployeesPrevent spread of influenza in workplaces by quarantining workers who had a co‐habiting family member with an ILIFull wages to employeeNon‐compulsory asking of workers whose family members developed an ILI to stay at home voluntarily on full wages.Daily measuring of temperature before leaving work.Where symptoms were doubtful, industrial physician made judgement.Company doctors provided input on cancelling of stay‐at‐home orders as required.Health management department oversaw the procedures and decisions. Mode of advice to employees not described.Car industries in JapanStay‐at‐home order for 5 days after resolution of ILI symptoms or 2 days after alleviation of fever over 7.5 monthsStrict standard for cancelling of stay‐at‐home orders described.None described.Recording of compliance with stay‐at‐home request100% compliance to stay at home reported.
Young 2021(additional source: Denford 2022)Daily contact testing (DCT) with Lateral Flow Device (LFD) for contacts of COVID‐19 casesStudents and staff from secondary schools and further education collegesProvide a quicker, more convenient and alternative testing option and policy for COVID‐19 close contact testing in schools, as an alternative to self‐isolationSARS‐CoV‐2 Lateral Flow Device (LFD) (Orient Gene, Huzhou,China)[47]In addition to twice weekly asymptomatic testing with LFD according to national policy:students and staff who were close contacts[48] of students or staff members who had a positive LFD or PCR were identified and offered daily LFD testing on arrival at school or college each morning (if asymptomatic and no household member isolating due to testing positive for COVID‐19)
Participants swabbed own nose (anterior nares), supervised by trained staff. Swabs tested by school staff using LFC
Contacts with negative LFC attended education but were asked to self‐isolate at home after school and on weekends/holidays
Contacts with 5 negative tests (tests done over 7 consecutive days) including one on or after the 7th day of testing were released from self‐isolationContacts with positive test were required to self‐isolate for 10 days, along with their contacts. Their school‐based contacts were identified and process repeatedA study worker was funded at each school but role not specifiedSchool staff tested the swabs that were taken by studentsStudy staff trained according to national NHS Test and Trace standard process supervised LFD testingIndividually and face to face172 secondary government funded, residential, special and independent day schools and further education colleges in EnglandMarch to May 2021Daily contact testing was performed at arrival at school each morningDay 1 of testing began the day after a case was identifiedTesting was done over 7 consecutive days (allowing for no testing on weekends)Schools actively participate between 19 April 2021 to 27 June 2021 (considered periods of low to moderate COVID‐19 incidence)When testing could not start immediately following identification of a case (e.g. due to a weekend), testing could start within 3 days of case identificationNone reportedDaily participation rates in IG measured per day and per participantCompliance was calculated / school / week, and participant type, (= sum of all study school days of individuals eligible for DCT returning a test result or already having completed follow up each day, divided by the sum of individuals eligible for DCT.Qualitative interviews conducted to understand reasons for participation and not (reported separately in Denford 2022)Testing did not occur on 15.8% of person‐school‐days due to school or public health agency directivesIG participation rate: 42.4% with marked variation between schools (range 0% to 100%).See Figure 2 for non‐participation reasons breakdown (e.g. testing kit unavailable, whole cohort moved to isolation).Staff more likely to participate than students.See Figure 2 for participation by school type breakdown“Although contacts at government‐funded schools with students 11–16 years old with a low proportion of free school meals were most likely to participate, other school types were similar, such that differences in participation related to factors other than school type.” (p. 1227)Qualitative analysis of interviews indicated daily testing may be feasible and acceptable but needs improved communication to students and parents about rationale, test interpretation and actions (Denford 2022)
Other (miscellaneous/multimodal) interventions
Ashraf 2020(additional sources: Arnold 2013, Luby 2018, Parvez 2018, Rahman 2018, Unicomb 2018)6 active interventions of Water, sanitation, hygiene (WASH) and nutrition components:A. Water (W)B. Sanitation (S)C. Handwashing (H)D. Water + sanitation + handwashing (WSH)E. NutritionF. Nutrition + WSH (WSHNResidents of households of village compounds and for some interventions, particularly pregnant women and their infants and children < 5 yearsImprove environmental conditions to interrupt transmission of respiratory pathogens and improve child malnutrition thereby reducing childhood respiratory illness and improving childhood morbidity based on the Integrated Behavioural Model for Water Sanitation and Hygiene[33] and 2 years of iterative testing and revision.Intervention specific behavioural objectives:W: drink treated and safely stored waterS: safe faeces disposalH: HW with soap at key timesN: age‐appropriate nutrition birth to 24 monthsFree technologies and supplies:W: chlorine (sodium dichloroisocyanurate) tablets (Aquatabs, Medentech, Wexford, Ireland)‐ 10 L insulated safe storage vessel (Lion Star Plastics, Sri Lanka) with a lid and tap for drinking water per household S: Dual‐pit pour flush latrines with water seals for all compound households. Each pit had 5 concrete rings 0.3 m high;‐ Potties[34] (RFL, Bangladesh)‐ Sani‐scoops[35] (locally developed hand‐tool made for the trial for removal of faeces from compound) for households with index children H: 2 HW stations, 1 water reservoir near kitchen (16 L) and 1 near latrine (40 L), each with basins for rinsing with a soapy water bottle (RFL, Bangladesh) and detergent sachets for index households[36] N: supply of lipid‐based nutrient supplements (LNS, Nutriset; Malaunay, France) (for 6 to 24 months olds) 2 10g sachets per day per child; (118 kcal, 9.6g fat, 2.6g protein, 12 vitamins and 10 minerals)Cost: USD 0.08/day18‐month shelf life Stipends for CHWs (USD 20/month for 24 months) delivered through mobile phone network to ensure timely payments Promoter’s guide for visits for each relevant intervention including:‐ visit objective,‐ target audience‐ steps and materials to be used CHW ID badges Cell phones for CHW supervisors Training Plan and Manual for CHW supervisors covering:i) basic training‐ introduction of project, CHW roles and responsibilities, introduction to behaviour‐change principles based on the IBM‐WASH theoretical framework and interpersonal and counselling communication skills.ii) Intervention‐specific trainingiii) classroom practice / role playingProvision and delivery of supplies or installations as described in Materials column according to intervention type or combination. Interventions deployed so that they were in place before index children were born In combined intervention arms, the sanitation measures were delivered first, followed by handwashing, then water treatment. Household visits and community discussions based on behaviour change strategy by CHWs (paid a monthly stipend), including interactive sessions for developing solutions to improve practice. Key recommendations per IG:
 W: children drink treated, safely stored water from vessel (filled vessel with added 1 33 mg tablet, wait 30 min before drinking) S: family use double pit latrines, potty train children and how to safely dispose of faeces and clean and maintain latrines H: family wash hands with soap after defecation, after cleaning a child who has defecated, before eating or before feeding a child, and before food preparation N: recommendations for exclusive breastfeeding up to 180 days and maternal and infant nutrition to mothers and index children; introduce diverse complementary food at 6 months; feed LNS from 6 to 24 months, mixed into the child’s food (not intended as a replacement for breastfeeding or complementary foods). Messages adapted from the Alive & Thrive programme[37] On household visits, following a structured plan, CHWs greeted targeted household members, checked presence and functionality of relevant hardware and signs of use, observed recommended practice using a guide.CHWs used discussions, video dramas, storytelling, games and songs and provided training on hardware maintenance, where applicable Adherence observed and measured by separate team Supervision meetings of CHWs and periodic internal monitoring of their performance Intervention Delivery Team managed delivery through regular team phone calls, field meetings, field reports and liaison with relevant government and other stakeholders. It co‐ordinated CHWs to ensure rapid identification of issues with delivery. Including a dedicated training officer, it also trained the CHW supervisors who then trained the CHWs under their supervision (“train the trainer” approach)540 CHW or ‘promoters’ who were local women and residents of study villages recruited through transparent merit‐based selection methods and consultation with community leaders CHWs had completed minimum of 8 years formal education, lived within walking distance of IG cluster and passed a written and oral examination. They attended multiple training sessions and quarterly refreshers. Training covered active listening, strategies for developing collaborative solutions and technical aspects of interventions (see Table 1 of Luby 2018 for more details) CHWs were trained by 47 CHW supervisors who received direct training on intervention delivery Hardware installation team (n = 18) 9 field research officers The Intervention Delivery Team[38] co‐ordinated delivery including CHWs, overseen by Principal Investigators with consultation from Technical Advisory Group(see Unicomb, 2018) Dedicated Training Officer and Communication Development officer Adherence observed by separate team who received formal 21 day trainingMostly face to face in groups and individually with some activities by phoneHouseholds and compounds (n = 5551) of rural villages in Gazipur, Kishoreganj, Mymensingh and Tangail Districts in Bangladesh Households spread across 0.2 to 2.2 km radius2 years from May 2012 6 to 8 households / CHW 1:12 supervisor to CHW ratio CHWs visited households 1 / week for first 6 months, then at least 1 / fortnight Promoter training:Initial:W, S, HW: 4 days;N, WSH: 5 days;WSHN: 9 days Refresher training: 1 day each 21 day training of adherence team Monthly CHW supervisor meetingsCHWs identified and addressed any barriers that arose through ongoing dialogue with caregivers CHWs met with supervisors monthly to adapt technology and behaviour‐change approaches to meet evolving conditions CHW supervisors available by cell phone as needed Training of promoter varied in content and length depending on intervention type Potties provided if children < 3 yearsS: latrine pits adapted when insufficient space (2% of cases) Functional water seals count was low (< 80% benchmark) in initial months which triggered a rapid response which improved uptake (Rahman 2018); households were using own latrines with broken water seals in parallel with trial latrines so pre‐existing latrines were closed, visits by CHWs were increased and water‐seal removal or breakage was discouragedInitial professional trainer for CHW training did not engage trainees enough so replaced with internal training resource group Due to observation of intervention fatigue reported by CHWs and sub‐optimal practices observed, new behaviour change activities were developed (e.g. further technology use, increasing self‐efficacy and roles for men)Measured by a separate trained team (university graduates) at regular intervals using a priori benchmarks:a) surveys and spot checks in 30 to 35 households / IG / per month, over 20‐month period;b) 5‐hours of structured observations in 324 IG and 108 control households, approximately 15 months after interventions commenced. Measured:W: Presence of stored drinking water with detectable free chlorine (> 0.1 mg/L)S: a latrine with functional water seal, sani‐scoop accessibilityH: presence of soap at primary HW stationsN: reported consumption of LNS sachets See Rahman 2018 for more details (Table 1) Continuous oversight and periodic monitoring of CHWs performance (CHW replaced within 1 month of attrition or critically low performanceCHWs visited more than planned (5 to 7 / month) which researchers suggest may have affected uptake Reported “high adherence to all interventions” with “marked differences in promoted behaviors from the control group at both year 1 and year 2,” with over 75% adherence in the single IG and combined IGs.Similar adherence in single W, S, H and N IGs compared with WSH and WSHN S: observed use of latrines: 94% to 97%; child sanitation practices (37% to 54%)H: HW with soap in IG more common after toilet use (67% to 74%) versus 18% to 40% in non‐IGs and after cleaning child’s anus (61% to 72%) but low before food handlingW: > 65% mothers and children observed drinking chlorine‐treated water from safe containerN: LNS feeding > 80% 33 low performing CHWs discontinued See Luby 2018, Parvez 2018, Arnold 2013, Unicomb 2018 for more details
Farr 1988a
trial 1 2 active interventions in addition to control of no tissues: A. Virucidal nasal tissues
 B. Placebo tissuesFamiliesReduce transmission of viruses from hand contamination via hand‐to‐hand contact or large‐particle aerosol through tissues for nose blowing and coughs and sneezes3‐ply tissues with:A. 5.1 mg/inch2 (2.54 cm2) of the virucidal mixture (58.8% citric acid, 29.4% malic acid, 11.8% sodium lauryl sulphate)B. 3 mg/inch2 (2.54 cm2) of saccharin applied uniformly to all 3 plies of the tissue
 Tissues prepared by Kimberly‐Clark Corporation, Neenah, WI, USA.Family visits to distribute tissues Weekly contact of mother Families instructed to only use supplied tissues.Nurse epidemiologist visited families.Face‐to‐face visits to families and individuals in families (especially mothers)Communities in the USA6 months overall Monthly family visits Weekly contact with motherNot describedNot describedFamily visits and weekly contact with mother to encourage complianceNot described
Farr 1988b
trial 22 active interventions (no control): A. Virucidal nasal tissues B. Placebo tissuesFamiliesReduce transmission of viruses from hand contamination via hand‐to‐hand contact or large‐particle aerosol through tissues for nose blowing and coughs and sneezes2‐ply tissues containing:A. 4.0 mg/inch2 (2.54 cm2) of antiviral mixture (53.3% citric acid, 26.7% malic acid, 20% sodium lauryl sulphate)B. 3 mg/inch2 (2.54 cm2) of succinic acid, malic acid, sodium hydroxide, and polyethylene glycolTissues prepared by Kimberly‐Clark Corporation, Neenah, WI, USA.Family visits to distribute tissues and encourage compliance Weekly contact of mother Families instructed to only use supplied tissues.  Nurse epidemiologist visited families monthly. Study monitor visited bimonthly.Face‐to‐face visits to families and individuals in families (especially mothers)Communities in the USA6 months overall Monthly family visits Weekly contact with mother Bimonthly study monitor visitNone described.None described.Bimonthly study monitor visits to encourage compliance as well as monthly and weekly contact by nurseIn 124/222 families, 1 or more family members reported not using the tissues regularly and/or reported having side effects from the tissues.
Fretheim 2022a
(additional source: Fretheim 2022b (protocol)GLASSY (GLasses Against transmission of SARS‐CoV‐2 in the communitYAdult members of the public who did not regularly wear glasses and who owned or could borrow glasses to use (e.g. sunglasses)Provide a simple, readily available, environmentally friendly, safe and sustainable means of personal protection from infection with respiratory viruses including SARS‐CoV‐2Instructions via online portal Regular eyewear, e.g. sunglasses owned by participant or that could be borrowed by participantRequest to wear sunglasses or other types of glasses when outside home and close to others in public spaces for 14 daysResearch teamIndividually Instructions provided via email and online portal (Nettskjema‐platform)accessed via web‐page hosted by the Norwegian Institute of Public HealthOutside the home, e.g. on public transport, in shopping malls (inNorway)14 days when outside and close to others in public spaces Over 11 to 12 week period (February – April 2022)Could borrow glasses if did not own anyNone reported.No contact was made with participants between enrolment and data collection.Reported use of glasses often, almost always, or always:IG: 71%CG: 11% Negative experiences (especially fogging with mask use):IG: 21/76
Longini 1988 2 active interventions (no control): A. Virucidal nasal tissues B. Placebo tissuesHouseholds and their familiesPrevent intrafamilial transmission of viral agents in a community settingTreated tissues of 3‐ply material identified with no specific identifiers (Kimberly‐Clark Corporation) with inside layer containing:A. citric and malic acid plus sodium lauryl sulphate;B. succinic acid.Tissues delivered to households with specific instructions on use (all purposes, when blowing nose, coughing or sneezing) and to discard after use and to help young children use tissues if develop a cold.Tissues assigned by study sponsor (Kimberly‐Clark Corporation).Supply of tissues throughout 5‐month trial periodHouseholds in the USA5 months' overall supplyResupply of tissues as requiredNone described.Reported use of tissues “not at all, some of the time, most of the time, or all of the time”Reported use “all of the time”:A. versus B.82% versus 71%
Chard 2019(additional details from Chard 2018)Water, Sanitation, and Hygiene for Health and Education in Laotian Primary Schools (WASH HELPS)Primary schools and their studentsPrevent the spread of pathogens within schools through improved water supply and hygiene facilities and improved WASHhabits in children at home and throughout the life courseFor each school:Water supply for school compound: (borehole, protected dug well with pump, or gravity‐fed system) Water tank to supply toilet and hand‐washing station School sanitation facilities (3 toilet compartments) Hand‐washing facilities:2 sinks with tapped water and supply of soap available (1 bar of soap/pupil) 3 group hand‐washing tables with soap and water At least 1 drinking water filter per classroom Schedules of daily group hand‐washing, compound and toilet cleaning Cost per school: USD 13,000 to 17,500Provision of school:Water supply, sanitation facilities, hand‐washing facilities (individual and group), drinking water filters Behaviour change education and promotion including daily group hygiene activities Daily hand‐washing and cleaning schedulesUNICEF paid for materials. School and teachers conducted daily hand‐washing activities with children.Students participated in daily group cleaning activities.Facilities provided within schools. Children participated in group hand‐washing and cleaning.Primary schools and their classrooms (in Laos)  One‐off provision of water and hygiene facilities Daily hand‐washing activities and cleaning for 1 school year Cleaning schedules posted in at least 1 classroom near toilet.Water supply tailored to the school requirements/environment. Sanitation facilities provided as needed and designated for boys, girls, and students with disabilities.Rain water tank provision affected by rain water supply, so changed to tanks with motorised hand pumps or gravity‐fed water supply systems. Theft and animal consumption of supplied soap reduced supply.Unannounced visits every 6 to 8 weeks for structured observations to measure fidelity and adherence Fidelity Index score (0 to 20): for hardware provided see Table 1 in paper and protocol Adherence index: student report of behavioural outcomes index score (0 to 4)Fidelity: 30.9% across all schools and visitsAdherence: 29.4%Hardware provision: 87.8% of schoolsSchool‐level adherence: 61.4%Group compound cleaning: 94.8%, toilet use: 75.5%, group toilet cleaning: 68.3%, group hand‐washing: 48.7%, individual hand‐washing with soap after toilet use: 23.9%. Further details (Chard 2018)
Hartinger 2016 Integrated environmental home‐based intervention package (IHIP)Households and their householders including childrenReduce infections and improve child growth in households in rural communities with limited facilities through a multi component, low‐cost environmental intervention to improve drinking water, sanitation, personal hygiene, and household air quality developed in pilot (Hartinger 2011; Hartinger 2012) using a participatory approach that addressed local beliefs and cultural viewsPer household: "OPTIMA‐improved stove": improved ventilated solid‐fuel stove Kitchen sink with in‐kitchen water connection providing piped water Point‐of‐use water quality intervention applying solar disinfection to drinking water Community engagement with local and regional stakeholders in design and development Provision of stoves, kitchen sinks, and plastic bottles for solar water treatment, and hygiene education Training of mothers/caretakers in:‐ solar drinking‐water disinfection (SODIS)[39] according to standard procedures‐ hand hygiene (washing own and children’s hands with soap at critical times[40])‐ advice to separate animals and their excreta from the kitchen environment Project‐initiated repairs Health promoters hired local elementary school teachers and implemented and promoted the interventions. 4 teams of field staff conducted spot‐check observations.Face‐to‐face and to individual households; mode of delivery of training as individual or group not describedHouseholds in rural communities in PeruStoves and sinks installed over initial 3 months. Monthly reinforcement over 12 months of SODIS, child and kitchen hygiene Weekly spot checks of compliance Repairs after 9 months Environmental samples test middle and end of 12‐month surveillance.  Tailored to particular household facilities and environments as needed and to local beliefs and cultural customs Repairs to stoves as needed and checked at 9 monthsNot describedWeekly spot‐check observations of household hygiene and environmental health conditions (e.g. presence of SODIS bottles on the roof or kitchen) using a checklist Monthly self‐report by mothers of stove and sink use  SODIS use:60% initially and 10% at end of study Self‐reported use by mothers: 90% with slight decrease at end Self‐reported stove use: 90% daily Sink use: 66% daily 35% of stoves needed minor repairs,1% needed major repairs. Best‐functioning stoves achieved mean 45% and 27% reduction of PM2.5 and CO, respectively, in mothers’ personal exposure.
Huda 2012Sanitation Hygiene Education and Water Supply in Bangladesh (SHEWA‐B)Villages and their households with a child < 5 years oldReduce illness in children < 5 years by improving hygiene practices, sanitation and water supply and treatment in their householdMaterials for training of community hygiene promoters and promotion activities including flip charts and flash cards with messages alerting participants to presence of unobservable “germs” and practices to minimise germsSee Box 1 in paper for 11 key messages.[41]      Engaging local residents under guidance of local NGOs to develop community action plans addressing:Latrine coverage and usageAccess to and use of arsenic‐free waterImproved hygiene practices, especially hand‐washing with soap Recruitment and appointment of community hygiene promoters Household visits, courtyard meetings, and social mobilisation activities (e.g. water, sanitation and hygiene fairs, village theatre, group discussions in tea stalls (the social meeting point for village men)) by community promoters Structured observation in householdsCommunity hygiene promoters (local residents with at least 10 years' schooling trained for 10 days on behaviour change communication in water, sanitation, and hygiene)Face‐to‐face delivery to groups (villages and households) and individualsVillages and households in districts of Bangladesh Community activities held in villages. Meetings held in courtyards of groups of households. Household visits  18 months overall Expected household visit and courtyard meeting every 2 months Hand‐washing opportunities: after own or child’s defecation,prior to preparing and serving food, prior to eating and feedinga child  Community action plans developed for and by local residents.Not describedStructured observation of hand‐washing and child faeces disposal behaviour in households and spot checks of type of household water and sanitation facilitiesHW:Food‐related:No significant difference from baseline to 18 months;IG versus CGAfter anus cleaning: 36% versus 27%Defecation: 30% versus 23% No access to latrine decreased from 10.3% to 6.8%. No significant improvement in access to improved latrines, solid waste disposal, drainage systems, and covered containers for water storage
Ibfelt 2015 Disinfection of toysDaycare nurseriesReduce transmission of pathogens via shared toys in daycare environment through regular disinfection treatmentDisinfectants:Turbo Oxysan (Ecolab, Valby, Denmark) for washing machinesSirafan M, Ecolab (1% to 3% benzalkonium chloride, 1% to 3% didecyldimethylammonium chloride, and 5% to 7% alcohol ethoxylates) for immersion or wipingCollection and commercial cleaning of toys from nurseries:
‐ linen and toys suitable for washing machines were washed at 46 °C and subsequently disinfected‐ toys not suitable for washing machines immersed in disinfectant or wiped with microfibre clothCommercial cleaning company: Berendsen A/S, Søborg, DenmarkCleaning companies collected the toys and linen and cleaned them offsite, then returned them.Daycare nurseries in Denmark Commercial industrial cleaning facility2 to 3 months overall Cleaning every 2 weeksStaggered cleaning to ensure children had toys to play with whilst others were being cleanedNone described.None described.None described.
Najnin 2019 (see also Qadri 2015 for further details)2 active interventions: A. Combined cholera vaccine and 'behaviour change communication' intervention B. Cholera vaccine‐alone group Low‐income households and compoundsPrevent or reduce transmission of respiratory illness based on the Integrated Behavioural Model for Water Sanitation and Hygiene (IBM‐WASH) theoretical framework (Dreibelbis 2013; Hulland 2013)A. and B.Cholera vaccineShanChol™ (Shantha Biotechnics‐Sanofi, India) A. Following hardware per compound:a. Hand‐washing hardware:(i) Bucket with a tap (provided free of charge)(ii) Soapy water bottle (mixture of a commercially available sachet of powdered detergent(∼USD 0.03) with 1.5 L of water in a plastic bottle with a hole punched in the cap) supplied by participating compounds(iii) Bowl to collect rinse water afterwashing hands (see photo in text or in Najnin 2017 doi.org/10.1093/ije/dyx187) b. Water treatment hardware:Dispenser containing liquid sodium hypochloriteSee Figure 2 in Najnin 2017 for photos of both doi.org/10.1093/ije/dyx187and more details. Participants own water vessels for water treatment Print materials for behaviour change to compounds and householdsA. and B.Provision of cholera vaccine (2 doses at least 14 days apart) Provision of hand‐washing hardware and behaviour change communication activities Encouragement of hand‐washing after defecation, after cleaning child’s anus, and before preparing food Encouragement to add chlorine to own water vessels Benefits were again explained. Follow‐up visits by health promoters Dushtha Shasthya Kendra (DSK), an NGO, delivered the hardware and behavioural intervention (through community health promoters). Separate data collectors observed soap availability.Hand‐washing and water treatment hardware mostly delivered at the compound level in person. Behaviour change communication messages were delivered both at compound and household levels.Households and compounds (where severalhouseholds share a common water source, kitchen,and toilets) in BangladeshBehaviour change communication messages delivered first (within 3 months of cholera vaccination). Point‐of‐use water hardware provided 3 months later. Follow‐up health promoter visits 3 times in 2 months after hardware installation, then 2 times/month (over nearly 2 years).Hardware‐related problems (breakage/leakage) were addressed on health promoter follow‐up visits.None described.Unannounced home visits by data collectors who observed presence of soap/soapy water and water in most convenient place for hand‐washing (either reserved in a container or available at the tap) Residual chlorine was measured indicating uptake of chlorine dispenser.Presence of soap / soapy water and water:A. Handwashing group compounds: 45% (1729 / 3886);B. Vaccine‐only group compound: 22% (438 / 1965);C. Control: 28% (556 / 1991) Residual chlorine present in stored drinking water of 4% (160/3886) of households in the vaccine‐plus‐behaviour‐ change compound and none in the other 2 compounds.
Swarthout 2020 (additional sources: Arnold 2013, Christensen 2015, Dentz 2017, Null 2018, Pickering 2019)6 active interventions of water, sanitation, and handwashing (WASH), and nutrition components:A. Water (W)B. Sanitation (S)C. Handwashing (H)D. Combined (WSH)E. Nutrition (N)F. Combined (WSHN)Residents of households of villages and for some interventions, particularly pregnant women (Mamas) and their infants and children < 5 years; Landowners of communal water sources and compound heads for latrine upgrades and constructionImprove environmental conditions to interrupt transmission of respiratory pathogens and improve child malnutrition thereby reducing childhood respiratory illness and improving childhood morbidity based on a literature review, a theory‐based approach (health belief, social cognitive theory and persuasion theory),[42],[43],[44] formative research and the WASH Benefits pilot RCT (Christensen 2015)Free technologies as appropriate to IG: W: water treated with sodium hypochlorite (1.25% solution / 2 mg/L) using chlorine dispensers installed at communal water source collection points or bottled chlorine (1L for 333 20‐l jerry‐cans worth)[45] provided to households in compoundsChlorine strips to test chlorine levels S: installation of new or improvement of existing latrines with plastic slab latrines with tight‐fitting lids; plastic potties and sani‐scoops H: 2 HW stations (2‐foot pedal‐operated jerry‐cans that dispensed soapy and rinse water), 1 near food preparation, 1 near latrine.Rinse water provided by households; bar soap for soapy water container N: 2 x 10 g sachets / day / child of lipid‐based nutrient supplementation (LNS) “Mwanzobora”, (Nutriset, Malaunay, France) (118 kcal/day and 12 essential vitamins and 10 minerals) See Figure 2 of Christensen 2015 for photos of examples of some of the materials Community meeting and household visit summary sheets (in Kiswahili and English) and list of materials provided as PDFs at osf.io/7j9sk/ Key messages and visual aids provided at osf.io/7j9sk/Including ~6 primary key messages per intervention, each with a series of specific topics, visual aids, and engagement activities (e.g. storytelling, mottos, etc.). Visual aids included:‐ cue card reminders‐ picture sheets for use by promoters‐ calendars for households with key messages‐ stickers for LNS box depicting appropriate feeding and storage Promoter Training Materials for trainers and trainees for each intervention for initial training and for refresher training including detailed PDF training manuals available at osf.io/7j9sk/ focusing on key hygiene messages, visitation scripts and visual aids and hardware for each intervention[46] Promoters’ supplies:Branded t‐shirt, mobile phone, job aids and intervention materials, payment ($US15/month for first 6 months, then $9/month thereafter), detailed plans for every visit (key messages, scripts for visual aids, instructions for activities) Provision and delivery of supplies or installations as described in Materials column according to intervention type or combination Provision of study materials to promoters Community meetings Household and community visits by promoters who:‐ delivered intervention‐specific behaviour change messaging focusing on themes of nurture, aspiration and self‐efficacy, considering convenience and cultural norms to improve adherence using scripts and visual aids;‐ provided instructions on hardware use and consumable supplies where applicable‐ advocated:W: drinking water treatment with sodium hypochloriteS: use of improved latrines for defecation and safe disposal of children’s and animals’ faeces and use of plastic potties by children < 3 years and sani‐scoops for faeces removalH: HW with soap before food preparation and after defecating (including assisting child); helped participants identify compound members to refill taps and manage barriers to use such as running out of soapN: early initiation of breastfeeding, exclusive breastfeeding 0 to 6 months and continued till 24 months; at 6 months, introduction of appropriate and diverse complementary foods; feeding frequency and during illness; supply of LNS to children 6 to 24 months and instruction to mix it was foods twice/day Promoters used visual aids to promote messages:‐ cue cards provided to Mamas at initial visits to hang on walls for reminders‐ picture sheets used by promoter to explain key concepts or messages‐ calendars provided to households during first compound visit‐ stickers attached to LNS box Adherence checking unannounced visits Initial training on intervention‐specific behaviour change messages and materials Refresher training Periodic observation and supportive supervision by study staffCommunity‐based health promoters nominated by their local communities and trained in the relevant intervention to be implemented Field enumerators assessed adherence in compounds Study staff trained promoters, provided periodic observation and supervision and monthly phone callsFace to face in groups (e.g. households or compounds) or individuals (mothers and their children)8246 households and 7960 compounds of rural villages in Bungoma, Kakamega, and Vihiga counties in western KenyaInstallation and supply of materials before community meetings Community meeting 6 weeks after enrolment Monthly visits (45 to 60 min in 1st year) by promoters over 2 years (2012 to 2014) Timing of visits detailed in procedures provided at osf.io/7j9sk/ W: 1 L bottle of chlorine / 6 months H: bar soap provided every 3 months N: LNS introduced at 6 months of age of child Promoter training:6 days single IGs.7 days combined IGs.Refresher training at 6, 12 and 18 months after initial training Supervision and observation of promoter by study staff at 2, 4, 9, 14 and 21 months and monthly phone callsTraining tailored for different interventions Troubleshooting of solutions to barriers to adherence by promoter and participants as needed Nutrition messaging was tailored to be age‐appropriate Materials provided in both in Kiswahili and English Chlorine dispensers located based on list of sources participants reported (at baseline) using for water collection Sani‐scoops and potties were to be washed by caregivers with soap and water after use and tools kept out of reach of children (see the visual aids provided to participants:osf.io/9r4kg/for potties andosf.io/mz2c6/for sani‐scoops)None describedParticipant reports of visits by promoters in past month Unannounced visits by staff to a random sample of at least 20% of participants in IGs at 2, 6, 10, and 19 months after the interventions began to confirm delivery of materials and monitor availability of intervention materials and recommended behaviours after the interventions began (Null 2018) W: monthly tests of chlorine concentration in stored water; negative results prompted discussions to address chlorination barriers S: participant report of access to improved latrine; field enumerators observed if latrine had plastic or cement slab or ventilation pipe; caregiver report that child faeces safely disposed H: field enumerator observed if water and soap available N: report of LNS sachets consumed by child in last week / 14All interventions delivered within 3 months of enrolment Increased adherence indicators of ≥ 30% higher in all IGs relative to the control in the first year Adherence was comparable between the Individual IGs compared with combined IGs. W: 5 chlorine dispensers installed / cluster Year 1: 74%Year 2: 37% households were visited by a promoter in previous month W:Year 1: 42%Year 2: 21% had detectable total chlorineCG: 3% S:Year 1 and 2: > 80% had latrine accessCG: 20% HW:Year 1: 77%Year 2: 21% had HW materialsCG: 9% N:Year 1: 95%Year 2: 115%of expected sachets consumed See Null 2018 for more details
Oral and/or nasal applications
Almanza‐Reyes 2021Mouthwash and nose rinse with ARGOVIT silver nanoparticles(AgNPs)Healthcare personnel (doctors, nurses, administrative staff) of a metropolitan hospital caring for patients diagnosed with atypical pneumonia and/or COVID‐19Reduce morbidity in healthcare professionals exposed to SARS‐Co V‐2 by inhibiting virus replicationPer participant:‐ 50 ml bottle of RGOVIT® AgNPs mouthwash and nasal rinse [Investigationand Production Center Vector‐Vita Ltd., Novosibirsk, Russia] (metallic silver 0.06%, polyvinylpyrrolidone 0.63%, hydrolyzed collagen 0.31%, distilled water 99% wt.)‐ water‐ cotton swabsIndividuals provided with spray bottle containing AgNPs solution with 1 wt% concentration (0.6 mg/mL metallic silver) and instructed to do 1 of the following or a combination:a) mix 4 to 6 spray shots (~ 0.5 mL) with 20 mL of water and gargle solution for 15 to 30 seconds at least 3 times/day (gargle) orb) do not dilute with water and cover the oral cavity evenly with 1 to 2 direct spray shots (spray)c) apply the same solution to the inner part of the nasal alae and nasal passage with cotton swab twice a day (nasal rinse)Researchers supplied materials and instructions Participants self‐applied the mouthwash and nasal rinse materialsIndividually and face to faceGeneral hospital in Tijuana, MexicoOver a 9 week period (April to June 2020) 4 to 6 spray shots of AgNP solution (0.5 mL) with 20 mL of water or 1 to 2 spray shots of solution without water for 15 to 30 seconds ≥3 times / day and 1 nasal lavage 2 times / dayParticipants could choose application methodNone describedWeekly self‐report of number of:daily gargles;mouthwashes with spray;mouthwashes by gargle + spray; andnasal rinsesMean applications/ day:Gargle only: IG: 2 (n = 28)CG: 2.14Spray only:IG: 2 (n = 34).Both gargle and spray:IG: 2 gargles, 4 sprays (n = 52)Nasal rinse:IG: 0.70 (n = 64)CG: 0.25
Gutiérrez‐García 2022Nasopharyngeal and oropharyngeal rinses with a neutral electrolyzed water (SES)COVID‐19 front‐line medical staff (nurses and physicians, males or females)Reduce risk of COVID‐19 in frontline unvaccinated medical staffSES (pH 6.5 to 7.5; REDOX potential 750‑950 mV;0.0015% of active species of chlorine and oxygen) provided by Esteripharma S.A. de C.VPer participant:‐ 4 plastic flasks of 240 mL oral SES(ESTERICIDE® Bucofaríngeo, COFEPRISregistration no. 1003C2013 SSA) with a graduated cap and‐ 4 plastic flasks of 30 mL nasal rinse (EsteriFlu®, COFEPRISregistration no. 308C2015 SSA), with a valve for sprayingWritten instructions provided to follow a prophylactic rinse protocol with SES 3 times/day for 4 weeks with advice on correct way to use the mouthwashes and sprays and the need to report possible side effects immediately:a) nasal cavity: 4 vertical sprays in each nostril, inhaled deeply at the time of each sprayb) oral cavity: mouthwash and gargle 10 mL for 60 seconds, then spit out In addition to standard COVID‐19 safety protocols requiring wearing of adequate personal protection equipment at all times,[49] frequent handwashing[50] and disinfection of secondary uniform and footwear[51] and bath at end of working dayNot clearly specified; leaders of nursing and other relevant healthcare department distributed the study information and were the point of contact and monitored the protocol so they may have distributed intervention materialsIndividually and face to faceMexican COVID‐19 hospital4 nasal sprays (~ 0.4 mL) and 10 mL mouthwash gargle for 60 seconds 3 times / day for 4 weeks (September to November 2020)None describedNone describedNone describedNone described
Goodall 20142 active interventions:

A. Vitamin D3 supplementation
B. Gargling water
 University studentsDecrease the incidence of URTI through increased vitamin D levels (associated with greater frequency and severity of URTI) and gargling (as preventative measure against URTI)A. Vitamin D3: container of 8 capsules of 10,000 IU (purchased from Euro‐Pharm
International Canada Inc.)
Weekly email reminder
B. Gargling: 30 mL of tap water 2/day
 A. Vitamin D: instructed to take 1 pill weekly
B. Gargling: instructed to gargle twice daily for 30 secondsAll participants received general
lifestyle and health advice on sleep, nutrition, hand hygiene, and exercise.Not specified, presumably the researchers, including a study pharmacistVitamin D3 supplied individually, but no further details.
Method of lifestyle and health advice provision also not described.
 In university student housing (in residences or off‐campus) in Canada2 months overall

Vitamin D3: weekly supplementation and email reminder
Gargling: 30 mL of water for 30 seconds twice daily
 None described.None described.None described.None described.
Ide 20142 active interventions (no control):
A. Green tea gargling
B. Water gargling
 High school studentsPrevent influenza spread and infection in high school students who are at increased risk from close interaction through gargling as a non‐pharmaceutical intervention, specifically green tea containing highly bioactive catechin (‐)‐epigallocatechin gallate, with possible anti‐influenza virus propertiesA. Bottled green tea (500 mL)
containing a catechin concentration of 37 ± 0.2 mg/dL, including approximately 18% (‐)‐epigallocatechin gallate (manufactured by the Kakegawa Tea Merchants Association).
Concentration measured by high‐performance liquid chromatography based on the average concentration in 10 bottles from the same production
lot (September 2011) used for gargling in the study.
B. Tap water
 A. Provision of green tea
B. Advice to gargle with tap water and not to gargle green tea during study
A. and B.
Advice to gargle at least 3 times/day (after arriving at school, after lunch, and after school)
Consumption of green tea and other tea was not restricted for
either group.
Safety monitoring carried out throughout the study (not further described).
 Materials supplied by researchers.
High schools’ vice principals and head teachers assisted with safety monitoring.
 Green tea supplied individually to students.
Mode of gargling advice not described.
 High schools in JapanGargling 3 times/day for 90 daysNone described.None described.Daily questionnaire included questions about daily
adherence to gargling regimen.
Adherence rate of gargling at
or above 75%, and absence of green tea gargling when in the
water gargling group.
 Gargling adherence rate: green tea group: 73.7%; water group: 67.2%
 
Satomura 20052 active interventions:A. Water gargling
B. Povidone‐iodine gargling
 Healthy adultsPrevent URTIs through gargling water alone, which may wash out pathogens from the pharynx and oral cavity through whirling water or through chlorine, or povidone‐iodine for its perceived virucidal propertiesA. Water
B. 15 to 30 times diluted 7% povidone‐iodine (as indicated by manufacturer)
 Local administrators instructed participants to:
‐ gargle dose of water or povidone‐iodine 3 times/day;
‐ maintain hand‐washing routine;
‐ not change other hygiene habits;
‐ not take any cold remedies;
‐ complete gargling diary.
Weekly monitoring of
hygienic actions and encouragement to keep up assigned intervention every weekLocal project administrators (18 healthcare professionals) provided instructions and monitoring and encouragement.Not specified, but likely to have been face‐to‐face and individually, at least initially for instructions18 healthcare sites in Japan (4 in northern region, 9 in central region, 5 in western region)60 days overall
1. Water gargling:
20 mL for 15 s at least 3 times/day
2. Povidone‐iodine gargling:
20 mL of dilution 3 times/day
 If diluted povidone‐iodine caused serious discomfort
or was not available, participants were allowed
to gargle with water instead.
 3 participants assigned to povidone‐iodine gargled with water instead as the povidone‐iodine “did not agree with them”.Completion of gargling diary: frequency of gargling and hand‐washing
Weekly monitoring and encouragement by local administrators
 9 participants did not complete diary.Average frequency of gargling / person / day:With water:A: 3.6B: 0.8Control: 0.9With povidone‐iodine:A.: < 0.1B: 2.9Control: 0.2
 

Assessment of risk of bias in included studies

Four review authors (EF/EB/GB/MJ) independently assessed risk of bias for the method of random sequence generation and allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), outcome reporting (attrition bias), and selective reporting (reporting bias). In addition, for the cluster trials, we assessed selection bias due to how recruitment of participants was conducted. Participants should be identified before the cluster is randomised or, if not, recruitment should be by someone masked to the cluster allocation. Further, we considered whether there were sufficient numbers of clusters in each treatment group to ensure comparable groups, and excluded one study from the analysis due to insufficient number of clusters. We used the Cochrane risk of bias tool to assess risk of bias, classifying each risk of bias domain as 'low', ‘high’, or ‘unclear’. The following were indications for low risk of bias:

method of random sequence generation: the method was well‐described and is likely to produce balanced and truly random groups;allocation concealment: the next treatment allocation was not known to participant/cluster or treating staff until after consent to join the study;blinding of participants and personnel: the method is likely to maintain blinding throughout the study;blinding of outcome assessors: all outcome assessors were unaware of treatment allocation;outcome reporting: participant attrition throughout the study is reported, and reasons for loss are appropriately described; andselective reporting: all likely planned and collected outcomes have been reported.

Measures of treatment effect

When possible, we performed meta‐analysis and summarised effectiveness as risk ratio (RR) using 95% confidence intervals (CIs). For studies that could not be pooled, we used the effect measures reported by the trial authors (such as RR or incidence rate ratio (IRR) with 95% CI or, when these were not available, relevant P values). Where multiple analyses were reported on the same outcome we chose the analysis based on preferences for: (1) an adjusted analysis (over an unadjusted analysis), and (2) an analysis based on a longer follow‐up period, or a greater number of outcomes events.

Unit of analysis issues

Many of the included studies were cluster‐RCTs. To avoid any unit of analysis issues, we only included treatment effect estimates that were based on methods that were appropriate for the analysis of cluster trials, such as mixed models and generalised estimating equations. Given this restriction, we used the generalised inverse‐variance method of meta‐analysis. Some cluster‐RCTs that did not report cluster‐adjusted treatment effects provided sufficient data (number of events and participants by treatment group and intraclass correlations) for us to calculate appropriate treatment effect estimates and standard errors using the methods described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021a). For studies with multiple treatment groups but only one control group, where appropriate, we adjusted standard errors upwards to avoid unit of analysis errors in the meta‐analyses. We did this by splitting the control group into equal sized groups and adjusting standard errors upwards to account for the reduced sample size of the control subgroups (Higgins 2021b).

Dealing with missing data

Previously, whenever details of studies were unclear, or studies were only known to us by abstracts or communications at meetings, we corresponded with first or corresponding authors. For this 2022 review, we did not contact authors of studies.

Assessment of heterogeneity

Aggregation of data was dependent on types of comparisons, sensitivity and homogeneity of definitions of exposure, populations and outcomes used. We calculated the I²statistic and Chi² test for each pooled estimate to assess the presence of statistical heterogeneity (Higgins 2002; Higgins 2003).

Assessment of reporting biases

Given the widely disparate nature of our evidence base, we limited our assessment of possible reporting biases to funnel plot visual inspection if we had > 10 included studies for any single meta‐analysis.

Data synthesis

If possible and appropriate, we combined studies in a meta‐analysis. We used the generalised inverse‐variance random‐effects model where cluster‐RCTs were included in the analysis. We chose the random‐effects model because we expected clinical heterogeneity due to differences in pooled interventions and outcome definitions, and methodological heterogeneity due to pooling of RCTs and cluster‐RCTs.

Subgroup analysis and investigation of heterogeneity

We conducted one post hoc subgroup analyses of adults (18 years +) versus children (0 to 18 years) for the comparison of hand hygiene versus control.

We did not conduct further investigation of heterogeneity due to insufficient numbers of studies included in the comparisons.

Sensitivity analysis

We conducted a sensitivity analysis for hand hygiene versus control where we included the most precise and unequivocal measure of viral respiratory illness reported for each included study.

Summary of findings and assessment of the certainty of the evidence

We created three summary of findings tables using the following outcomes: numbers of cases of viral respiratory illness (including ARIs, ILI, COVID‐like illness and laboratory‐confirmed influenza/SARS‐CoV‐2 or other respiratory viruses), and adverse events related to the intervention (Table 1; Table 2; Table 3). We planned to include the secondary outcomes of deaths; severity of viral respiratory illness as reported in the studies; absenteeism; hospital admissions; and complications related to the illness (e.g. pneumonia). However, these data were poorly reported in the included studies. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of evidence as it related to the studies which contributed data to the meta‐analyses for the prespecified outcomes (Atkins 2004). We used the methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), employing GRADEpro GDT software (GRADEpro GDT). We justified all decisions to down‐ or upgrade the certainty of the evidence in footnotes, and made comments to aid the reader's understanding of the review where necessary.

Results

Description of studies

See Characteristics of included studies and Characteristics of excluded studies tables. Five trials were funded by government and pharmaceutical companies (Aiello 2010; Aiello 2012; Chard 2019; Yeung 2011; Zomer 2015), and nine trials were funded by pharmaceutical companies (Arbogast 2016; Carabin 1999; Luby 2005; Nicholson 2014; Sandora 2005; Sandora 2008; Turner 2004a; Turner 2004b; Turner 2012).

Results of the search

For this 2022 update we found 2667 records through database and trial registry searching, as well as 738 record through citation searching. After removing duplicates we had 2936 records that underwent title and abstract screening. 
We identified a total of 202 titles in this 2022 update. We excluded 180 titles and retrieved the full papers of 35 studies, to include 11 new studies. See Figure 1.

1 Study flow diagram. (Figure not reproduced here; see the original article.)

Included studies

In this 2022 update we included 11 new studies (610,872 participants); randomised controlled trials (RCTs) (n = 5) or cluster‐RCTs (n = 6) published between 2020 and 2022. In total 78 studies are included in this review update. For detailed descriptions of the interventions of the included studies, see Table 4.

Eighteen trials focused on using masks (Abaluck 2022; Aiello 2010; Aiello 2012; Alfelali 2020; Barasheed 2014; Bundgaard 2021; Canini 2010; Cowling 2008; Ide 2016; Jacobs 2009; Loeb 2009; MacIntyre 2009; MacIntyre 2011; MacIntyre 2013; MacIntyre 2015; MacIntyre 2016; Radonovich 2019; Suess 2012). Thirteen of the 18 trials compared medical/surgical masks to no mask (control) (Abaluck 2022; Aiello 2010; Aiello 2012; Alfelali 2020; Barasheed 2014; Bundgaard 2021; Canini 2010; Cowling 2008; Jacobs 2009; MacIntyre 2009; MacIntyre 2015; MacIntyre 2016; Suess 2012). One study compared catechin‐treated masks to no mask (Ide 2016), and one study included cloth masks versus control (third arm in MacIntyre 2015). Three of the 18 trials were in healthcare workers (Ide 2016; Jacobs 2009; MacIntyre 2015), whilst the remaining trials were in non‐healthcare workers (students, households, families, or pilgrims). Only one trial was conducted during the H1N1 pandemic season (Suess 2012), and two trials were conducted during the SARS‐CoV‐2 pandemic (Abaluck 2022; Bundgaard 2021).

Five of the 18 trials compared N95 masks or P2 masks to medical/surgical masks (Loeb 2009; MacIntyre 2009; MacIntyre 2011; MacIntyre 2013; Radonovich 2019). All of these trials, except for one study that was conducted on household individuals (MacIntyre 2009), included healthcare workers either in a hospital setting, Loeb 2009; MacIntyre 2011; MacIntyre 2013, or an outpatient setting (MacIntyre 2009; Radonovich 2019).

One trial evaluated the effectiveness of quarantining workers of one of two sibling companies in Japan whose family members had developed an influenza‐like illness (ILI) during the 2009 to 2010 H1N1 influenza pandemic (Miyaki 2011). Another trial conducted during the SARS‐CoV‐2 pandemic in Norway investigated fitness centre access with physical distancing compared to no access (Helsingen 2021); and one cluster trial compared daily testing for contacts of individuals with SARS‐CoV‐2 compared to self‐isolation at home in English secondary schools (Young 2021).

Nineteen trials compared hand hygiene interventions with no hand hygiene (control) and provided data suitable for meta‐analysis. The populations in these trials included adults, children, and families, in settings such as schools (Biswas 2019; Stebbins 2011), childcare centres (Azor‐Martinez 2018; Correa 2012; Roberts 2000; Zomer 2015), homes/households (Cowling 2008; Cowling 2009; Larson 2010; Little 2015; Nicholson 2014; Ram 2015; Sandora 2005; Simmerman 2011), offices (Hubner 2010), military trainees (Millar 2016), villages (Ashraf 2020; Swarthout 2020), and nursing homes (Teesing 2021). None of the trials were conducted during a pandemic, although some of the studies were conducted during peak influenza seasons.

A further 10 trials that compared a variety of hand hygiene modalities to control provided insufficient information to include in meta‐analyses. Three trials were in children: one was conducted in daycare centres in Denmark examining a multimodal hygiene programme (Ladegaard 1999), and two trials compared a hand hygiene campaign or workshop in an elementary school environment in Saudi Arabia, Alzaher 2018, and Egypt, Talaat 2011. Three trials tested virucidal hand treatment in an experimental setting, Gwaltney 1980; Turner 2004a, and in a community, Turner 2012, in the USA. Feldman 2016 compared hand‐washing with chlorhexidine gluconate amongst Israeli sailors. One trial compared hand sanitiser packaged in a multimodal hygiene programme amongst office employees in the USA (Arbogast 2016). Two trials were conducted in a long‐term facility setting: one trial examined the effect of a bundled hand hygiene programme on infectious risk in nursing home residents in France (Temime 2018), and the other trial compared the effect of using hand sanitisers in healthcare workers on the rate of infections (including respiratory infections) in nursing home residents in Hong Kong (Yeung 2011).

Five trials compared different hand hygiene interventions in a variety of settings such as schools (Morton 2004, in kindergartens and elementary schools in the USA; Priest 2014, in primary schools in New Zealand; and Pandejpong 2012 in kindergartens in Thailand). One study was conducted in low‐income neighbourhoods in Karachi, Pakistan (Luby 2005), and one was conducted in a workplace environment in Finland (Savolainen‐Kopra 2012). A variety of interventions were used across these trials such as soap and water (Luby 2005; Savolainen‐Kopra 2012), hand sanitiser (Morton 2004; Pandejpong 2012; Priest 2014; Savolainen‐Kopra 2012), body wash (Luby 2005), and alcohol‐based hand wipes (Morton 2004), with or without additional hygiene education. There was considerable variation in interventions, and the information in the trial reports was insufficient to permit meta‐analysis.

Seven trials compared a combined intervention of hand hygiene and face masks with control. Four of these trials were carried out in households in Germany (Suess 2012), Thailand (Simmerman 2011), Hispanic immigrant communities in the USA (Larson 2010), and households in Hong Kong (Cowling 2009). Two trials were conducted amongst university student residences (Aiello 2010; Aiello 2012), and two trials in groups of pilgrims at the annual Hajj (Aelami 2015; Alfelali 2020). Moreover, six trials evaluated the incremental benefit of combining surgical masks in addition to hand hygiene with soap (Simmerman 2011), hand sanitiser (Aiello 2010; Aiello 2012; Larson 2010; Suess 2012), or both (Cowling 2009), versus mask or hand hygiene alone on the outcomes of ILI and influenza. Aelami 2015 investigated a hygienic package (alcohol‐based hand rub (gel or spray), surgical masks, soap, and paper handkerchiefs) with a control group.

Seven trials compared a multimodal combination of hand hygiene and disinfection of surfaces, toys, linen, or other components of the environment with a control (Ban 2015; Carabin 1999; Ibfelt 2015; Kotch 1994; McConeghy 2017; Sandora 2008; White 2001). Variation in scope and type of interventions and insufficient data in trial reports precluded meta‐analysis. All studies except for one were in children (McConeghy 2017), which was in a nursing home population).

Three trials included in two papers investigated the role of virucidal tissues in interrupting transmission of naturally occurring respiratory infections in households (Farr 1988a; Farr 1988b; Longini 1988). Four cluster‐RCTs implemented complex, multimodal sanitation, education, cooking, and hygiene interventions (Chard 2019; Hartinger 2016; Huda 2012; Najnin 2019). All four of these trials were conducted in low‐income countries in settings with minimal to no access to basic sanitation.

Three trials assessed the effect of gargling on the incidence of upper respiratory tract infections (URTIs) or influenza: gargling with povidone‐iodine (Satomura 2005), green tea (Ide 2014), and tap water (Goodall 2014). Two trials investigated the use of mouth/nasal washes on the incidence of SARS‐CoV‐2 infection in healthcare workers during the COVID‐19 pandemic (Almanza‐Reyes 2021; Gutiérrez‐García 2022). One trial investigated the use of glasses against the transmission of SARS‐CoV‐2 (Fretheim 2022a).

Ongoing studies

We identified four ongoing studies during the course of the COVID‐19 pandemic, of which one is completed, but unreported (NCT04471766). The trials evaluated masks concurrent with the COVID‐19 pandemic. Three trials on other interventions are ongoing (Brass 2021; NCT03454009; NCT04267952).

Studies awaiting classification

We identified five studies awaiting classification (Contreras 2022; Croke 2022; Delaguerre 2022; Loeb 2022; Varela 2022).

A previous RCT (NCT04296643) reported as ongoing in the last version has now been recently published but was not able to be included in the summary of findings pooled results (Loeb 2022). In a multicentre, randomised non‐inferiority trial of 1009 healthcare workers (HCWs) across four countries randomised to medical mask versus fit‐tested N95 respirators for direct care of COVID‐19 patients or long‐term care residents, laboratory‐confirmed SARS‐CoV‐2 was found in 10.46% (52/497) versus 9.27% (47/507) in the medical/surgical mask group and fit‐tested N95 respirator group (hazard ratio 1.14 (95% CI 0.77 to 1.69), respectively. There was a 1.19% absolute increase in risk of COVID‐19 with medical masks versus N95 respirator  95% CI (‐2.5% to 4.9%). There were 47 (10.8%) adverse events related to the intervention reported in the medical mask group and 59 (13.6%) in the N95 respirator group. The use of medical masks was found to be non‐inferior to N95 respirators in the direct care of COVID‐19 patients and the study crossed over into the more transmissible Omicron variant period of the COVID‐19 pandemic.

Excluded studies

We excluded a total of 180 studies. We identified 20 new studies for exclusion at the data extraction stage of this 2022 update, all of which appeared to be eligible at screening. Five of the 20 studies were ineligible due to evaluating treatments for patients with disease (Cyril Vitug 2021; Ferrer 2021; Meister 2022; Sanchez Barrueco 2022; Sevinc Gul 2022), two were excluded because they did not assess clinical outcomes (Costa 2021; Seneviratne 2021), four were excluded due to not assessing viral outcomes (Gharebaghi 2020; Giuliano 2021; Karakaya 2021; Kawyannejad 2020), five were excluded as they were experiments that did not measure any of our outcomes of interest (Ahmadian 2022; Dalakoti 2022; Egger 2022; Malaczek 2022; Montero‐Vilchez 2022); three were excluded because they were not RCTs (Chen 2022; Lim 2022; Mo 2022), and one was excluded as it was a report of another study (Munoz‐Basagoiti 2022).

Risk of bias in included studies

The overall risk of bias is presented graphically in Figure 2 and summarised by included study in Figure 3. Details on the judgements can be found in the descriptions of individual included studies (Characteristics of included studies table). Out of 78 included studies, only two were rated as low risk of bias for all domains. One of those studies compared two different types of masks (Radonovich 2019), and the other compared hand sanitiser to no treatment (Turner 2012). Notably, neither of these two studies was blinded, however, trial procedures were sufficiently robust that the risk of performance bias was low. Overall,approximately only 20% of the studies were rated as low risk of performance bias. This risk of bias domain was particularly problematic because most interventions studied could not be blinded from participants and/or investigators. The two risks of bias domains that were rated the least problematic were attrition bias and random sequence generation where around 50% of studies were rated as low risk of bias. Allocation concealment, blinded outcome assessment and selective reporting were rated as low risk of bias for around 40% of the included studies. Many of the included studies were cluster‐RCTs where the randomisation process was not well reported leading to ratings of unclear risk of bias.

2 'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included trials. (Figure not reproduced here; see the original article.)

3 'Risk of bias' summary: review authors' judgements about each risk of bias item for each included trial. (Figure not reproduced here; see the original article.)

Allocation

For this 2022 review, 10 of the 11 newly included studies provided adequate information on randomisation and were  judged to have low risk of bias (Abaluck 2022; Alfelali 2020; Almanza‐Reyes 2021; Ashraf 2020; Bundgaard 2021; Fretheim 2022a; Helsingen 2021; Swarthout 2020; Teesing 2021; Young 2021). Six of these studies described the use of a computerised random number generator (Almanza‐Reyes 2021; Bundgaard 2021; Helsingen 2021; Swarthout 2020; Teesing 2021; Young 2021). Almanza‐Reyes 2021 described the use of computer‐generated stratified block scheme, while Bundgaard 2021 reported the use of a computer algorithm stratified by the five regions of Denmark. In Fretheim 2022a, the investigators used a digital platform (Nettskjema) for recruitment, randomisation and allocation. Three studies mentioned the use of a random number generator, with no additional specifics (Helsingen 2021; Swarthout 2020; Teesing 2021), while Young 2021 mentioned that randomisation was performed in blocks of two and stratified using nine strata to ensure a sample representative of schools and colleges in England. Abaluck 2022 reported pairwise cross randomisation, whilst Ashraf 2020 reported using a block random number generator. Alfelali 2020 described using coin‐tossing by an individual who was not a member of the research team (i.e. a fellow pilgrim who was not a participant in the trial, a tour operator, or a medical volunteer). One study provided insufficient information to judge the sequence generation bias (Gutiérrez‐García 2022).

The success of randomisation was judged as low risk of bias in one study only that used an off‐site investigator to allocate groups (Ashraf 2020). Four new studies provided insufficient information to make a judgment on the adequacy of the process (Bundgaard 2021; Swarthout 2020; Teesing 2021; Young 2021). The remaining six newly included studies were judged as high risk of allocation bias (Abaluck 2022; Alfelali 2020; Almanza‐Reyes 2021; Fretheim 2022a; Gutiérrez‐García 2022; Helsingen 2021). In Abaluck 2022, there was a significant difference in the numbers of households included in each treatment group, suggestive of a lack of allocation concealment. Alfelali 2020 used coin tossing, which can lead to a large imbalance. In Almanza‐Reyes 2021 baseline prognostic factors (vaccination and frequency of handwashing) were unbalanced between the two arms. In Fretheim 2022a, a higher number of participants used face masks in the intervention group. In Gutiérrez‐García 2022 there as a significant age difference between the two groups. Helsingen 2021 described assigning the randomised sequence by a member of the research team, with no further description.

For the review published in 2020, information on sequence generation was overall poorly reported in most of the  included studies. Nineteen of the included studies provided adequate information on the randomisation scheme and were judged as at low risk of bias (Aiello 2012; Azor‐Martinez 2016; Azor‐Martinez 2018; Biswas 2019; Canini 2010; Correa 2012; Ide 2014; MacIntyre 2015; MacIntyre 2016; Millar 2016; Najnin 2019; Radonovich 2019; Ram 2015; Simmerman 2011; Stebbins 2011; Suess 2012; Talaat 2011; Turner 2012; Zomer 2015). Nine studies described the use of computerised sequence generation program/software (Aiello 2012; Azor‐Martinez 2018; Biswas 2019; Canini 2010; Millar 2016; Najnin 2019; Radonovich 2019; Talaat 2011; Turner 2012). One study used random number tables for sequence generation (Azor‐Martinez 2016). Three studies described using the random function in Microsoft Excel (Microsoft Excel 2018) (Correa 2012; MacIntyre 2016; Suess 2012). Two studies used statistical software to generate a randomisation allocation (MacIntyre 2015; Priest 2014). Two studies reported using block randomisation: Ram 2015 used block randomisation, and an independent investigator‐generated the list of random assignments, whilst Simmerman 2011 performed block randomisation. Stebbins 2011 used constrained randomisation, and Zomer 2015 reported using stratified randomisation by means of computer generation with a 1:1 ratio in each of the strata.

Fourteen studies reported insufficient information to permit a judgement on the adequacy of the process to minimise selection bias (Aelami 2015; Alzaher 2018; Arbogast 2016; Barasheed 2014; Chard 2019; DiVita 2011; Feldman 2016; Hubner 2010; Ibfelt 2015; McConeghy 2017; Miyaki 2011; Pandejpong 2012; Savolainen‐Kopra 2012; Yeung 2011). Six studies provided some description about sequence generation, but it was still unclear (Hartinger 2016; Huda 2012; Ide 2016; Little 2015; MacIntyre 2011; MacIntyre 2013). Huda 2012 mentioned random number tables, but it was unclear if this was for random selection or randomisation. Ide 2016 used computer‐generated randomisation, but the method was not stated. Hartinger 2016 used covariate‐constrained randomisation, but the method was not described. In Little 2015, participants were automatically randomly assigned by the intervention software, but the sequence generation was not described. Two studies used a secure computerised randomisation program (MacIntyre 2011; MacIntyre 2013), but the sequence generation was not described.

Three of the studies included in the 2020 review, were poorly randomised (Ban 2015; Nicholson 2014; Temime 2018). Ban 2015 included only two clusters, and the randomisation scheme was not reported. Nicholson 2014 used coin tossing, which can lead to a large imbalance. Temime 2018 used “simple randomisation” with no further description.

For the RCTs included in previous versions of the review, three were poorly reported with no description of randomisation sequence or concealment of allocation (Gwaltney 1980; Turner 2004a; Turner 2004b). The quality of the cluster‐RCTs varied, with four studies not providing a description of the randomisation procedure (Carabin 1999; Kotch 1994; Morton 2004; White 2001). We rated seven studies as at low risk of bias for sequence generation (Cowling 2008; Cowling 2009; Luby 2005; Roberts 2000; Sandora 2005; Sandora 2008; Satomura 2005), and a further six studies as at unclear risk of bias (Farr 1988a; Farr 1988b; Ladegaard 1999; Loeb 2009; Longini 1988; MacIntyre 2009).

Many of the newly included cluster‐RCTs did not report adequately on allocation concealment. Twenty‐one of these studies reported adequate allocation and were judged as at low risk of bias (Aiello 2012; Alzaher 2018; Azor‐Martinez 2016; Azor‐Martinez 2018; Biswas 2019; Canini 2010; Chard 2019; Goodall 2014; Ide 2014; Ide 2016; Little 2015; MacIntyre 2011; MacIntyre 2015; Nicholson 2014; Priest 2014; Radonovich 2019; Ram 2015; Savolainen‐Kopra 2012; Stebbins 2011; Suess 2012; Turner 2012). Aiello 2012 randomised all residence houses in each of the residence halls prior to the intervention implementation. Alzaher 2018 allocated schools prior to all schoolgirls attending selected schools being invited to participate. Azor‐Martinez 2016 allocated schools/classes prior to children's recruitment. Azor‐Martinez 2018 assigned clusters prior to recruitment. Biswas 2019 completed the allocation prior to individuals being recruited. Chard 2019 allocated schools prior to individuals being recruited. Goodall 2014 used opaque, sealed, serially numbered envelopes that were only accessed when two study personnel were present. Ide 2014 also reported using individual drawing of sealed, opaque envelopes to randomly assign participants to the study groups. MacIntyre 2011 randomised hospitals prior to inclusion of participants. In MacIntyre 2015, hospital wards were randomised prior to recruitment of individuals. Nicholson 2014 used coin tossing to assign communities to intervention or control arms. Radonovich 2019 used constrained randomisation to resolve any potential imbalance between covariates between the trial arms. Four studies reported the use of central randomisation: Canini 2010 used central randomisation by employing an interactive voice response system; Ide 2016 used central randomisation services; Little 2015 participants were automatically randomly assigned by the intervention software; and Ram 2015 described a central allocation through data collectors notifying the field research officer, who consulted the block randomisation list to make the assignment of the household compound to intervention or control. Savolainen‐Kopra 2012 randomised clusters by matching prior to the onset of the interventions. Four studies reported that allocation was assigned by personnel (investigator, physician, or statistician) unaware of the randomisation sequence (Priest 2014; Stebbins 2011; Suess 2012; Turner 2012). Twenty‐two studies reported insufficient information to permit a judgement on the adequacy of the process to minimise selection bias (Aelami 2015; Arbogast 2016; Ban 2015; Barasheed 2014; Correa 2012; DiVita 2011; Feldman 2016; Hartinger 2016; Hubner 2010; Huda 2012; Ibfelt 2015; MacIntyre 2013; McConeghy 2017; Millar 2016; Miyaki 2011; Najnin 2019; Pandejpong 2012; Simmerman 2011; Talaat 2011; Temime 2018; Yeung 2011; Zomer 2015). Two studies provided some information about allocation, but it was not enough to permit a judgement on the risk of bias (Barasheed 2014; Simmerman 2011). Barasheed 2014 randomised pilgrim tents using an independent study co‐ordinator who was not an investigator, but did not describe how this was done. Simmerman 2011 described using a study co‐ordinator to assign households to the study arm (after consent was obtained). Only one of the newly added studies was judged as at high risk of bias, where the random assignment was allocated by doctors enrolling the participants (MacIntyre 2016). Of the previously included RCTs, 14 provided no or an insufficient description of concealment of allocation (Carabin 1999; Farr 1988a; Farr 1988b; Gwaltney 1980; Kotch 1994; Ladegaard 1999; Larson 2010; MacIntyre 2009; Morton 2004; Roberts 2000; Sandora 2008; Turner 2004a; Turner 2004b; White 2001). We assessed all of the remaining studies as at low risk of bias (Canini 2010; Cowling 2008; Cowling 2009; Loeb 2009; Longini 1988; LLuby 2005; Sandora 2005;Satomura 2005). Aiello 2010 used the drawing of a uniform ticket with the name of each hall out of a container and was rated as at high risk of bias.

Blinding

Although blinding is less of a concern in cluster‐RCTs, the risk of bias is substantial when the outcomes are subjective and the outcome assessor is not blinded.

In this 2022 review, five RCTs (Almanza‐Reyes 2021; Bundgaard 2021; Fretheim 2022a; Gutiérrez‐García 2022; Helsingen 2021), and six cluster‐RCTs were all judged to have a high risk of detection bias (Abaluck 2022; Alfelali 2020; Ashraf 2020; Swarthout 2020; Teesing 2021; Young 2021).

We judged two of the newly included studies to have a low risk of detection bias as the outcome is laboratory‐confirmed (Alfelali 2020; Gutiérrez‐García 2022). One study provided insufficient information to enable judgment (Almanza‐Reyes 2021). The remaining eight of the 11 new studies have a high risk of detection bias (Abaluck 2022; Ashraf 2020; Bundgaard 2021; Fretheim 2022a; Helsingen 2021; Swarthout 2020; Teesing 2021; Young 2021). In Abaluck 2022, investigators dropped individuals for whom symptom data were missing. In addition, other outcomes were subjective and can be influenced by the unblinded mask promoters, and mask surveillance staff. Moreover, blood testing in the protocol specified baseline testing which was not done, and no further explanation was provided. In Ashraf 2020, although the data collection team was separate from the intervention team, they were not blinded, and the outcome was respiratory illness measured through caregiver‐reported symptoms. In Bundgaard 2021, case detection was based on patient‐reported symptoms on home tests. In Fretheim 2022a, the outcome was self‐reported positive COVID‐19 test result, notified to the Norwegian Surveillance System for Communicable Diseases (MSIS). However, the public policy requiring confirmatory PCR‐test had changed during the study, which may have affected reporting. In Helsingen 2021, although the outcome was a positive test for COVID‐19 based on SARS‐CoV‐2 ribonucleic acid, the samples were collected and sent by participants, and there was a difference in adherence in testing between the two groups. Swarthout 2020, Teesing 2021, and Young 2021 all had subjective outcomes and assessors were not blinded. As for the detection bias,  six of the newly included studies were considered to have a high risk of detection bias (Bundgaard 2021; Gutiérrez‐García 2022; Helsingen 2021; Swarthout 2020; Teesing 2021; Young 2021. In Bundgaard 2021, case detection was based on patient‐reported symptoms and results from home point‐of‐care (POCT) testing. The primary outcome of Gutiérrez‐García 2022 was participants' self‐reported symptoms. Case detection in Helsingen 2021 was based on a home‐test kit. Swarthout 2020, Teesing 2021, and Young 2021 had subjective outcomes.

In the 2020 review, we judged 36 studies to have a high risk of bias (Aiello 2012; Abaluck 2022; Alfelali 2020; Almanza‐Reyes 2021; Alzaher 2018; Arbogast 2016; Ashraf 2020; Azor‐Martinez 2016; Azor‐Martinez 2018; Ban 2015; Biswas 2019; Bundgaard 2021; Carabin 1999; Chard 2019; Correa 2012; Cowling 2008; Gutiérrez‐García 2022; Helsingen 2021; Ide 2014; Kotch 1994; Ladegaard 1999; Little 2015; MacIntyre 2011; MacIntyre 2015; MacIntyre 2016; McConeghy 2017; Najnin 2019; Nicholson 2014; Ram 2015; Sandora 2008; Savolainen‐Kopra 2012; Swarthout 2020; Teesing 2021; Temime 2018; Young 2021; Zomer 2015). We assessed five cluster‐RCTs as at low risk of bias. Farr 1988a and Farr 1988b were double‐blinded studies and were judged as at low risk of bias. MacIntyre 2013 and Simmerman 2011 reported laboratory‐confirmed influenza, and blinding would not have affected the result. In Miyaki 2011 the self‐reported respiratory symptoms were confirmed by a physician.

We judged four cluster‐RCTs to have a low risk of detection bias because the outcome was laboratory‐confirmed influenza (Alfelali 2020; Barasheed 2014; Suess 2012), or physician‐confirmed ILI, Pandejpong 2012. Another two cluster‐RCTs were judged to have a low risk of bias because outcome assessors were blinded (Abaluck 2022; Ashraf 2020). One RCT (Almanza‐Reyes 2021) and two cluster‐RCTs (Talaat 2011; Yeung 2011) provided insufficient data to judge the effect of non‐blinding. Talaat 2011 included outcomes that were both self‐reported ILI and laboratory‐confirmed influenza. In Yeung 2011 the detection of cases was based on records for hospitalisation related to infection (including pneumonia). Eleven cluster‐RCTs were not blinded, but we judged the primary outcome to be unaffected by non‐blinding. Seven trials reported laboratory‐confirmed influenza (Aiello 2012; Cowling 2009; Larson 2010; Loeb 2009; MacIntyre 2009; Millar 2016; Stebbins 2011). Four studies reported self‐reported outcomes (Canini 2010; Priest 2014; Roberts 2000; Sandora 2008), but outcome assessors were not aware of the intervention assignment. Five RCTs were double‐blinded and were judged as at low risk of bias (Goodall 2014; Ide 2016; Longini 1988; Luby 2005; White 2001), whilst two studies were single‐blinded where investigators, Radonovich 2019, or laboratory personnel, Turner 2012, were blinded. Four RCTs were not blinded and were judged as at high risk of bias given the subjective nature of the outcome assessed (Hubner 2010; Ibfelt 2015; Jacobs 2009; Satomura 2005). Turner 2004a and Turner 2004b were double‐blind studies, but insufficient information was provided to assess the risk of bias.

Incomplete outcome data

In this 2022 review, six of the 11 newly included studies had reasonable attrition and provided sufficient evidence about participant flow throughout the study and reasons of loss to follow‐up, and hence were assessed as having a low risk of attrition bias (Alfelali 2020; Ashraf 2020; Bundgaard 2021; Fretheim 2022a; Gutiérrez‐García 2022; Swarthout 2020). Two studies provided insufficient information to assess the attrition risk (Almanza‐Reyes 2021; Teesing 2021). The remaining three studies were judged at high risk of attrition bias. In Abaluck 2022, laboratory testing results were only available for 40% of the symptomatic participants. In Helsingen 2021, more people in the control group withdrew from the study and reasons for withdrawal were not provided. In the Young 2021 study there was high attrition at different rates between the two groups.

In the 2020 review, we assessed 26 newly included trials as having a low risk of attrition bias, with sufficient evidence from the participant flow chart, and explanation of loss to follow‐up (which was minimal) similar between groups (Aiello 2012; Alzaher 2018; Arbogast 2016; Azor‐Martinez 2018; Barasheed 2014; Canini 2010; Chard 2019; Correa 2012; Goodall 2014; Hartinger 2016; Hubner 2010; Ide 2014; Ide 2016; MacIntyre 2011; MacIntyre 2013; MacIntyre 2015; MacIntyre 2016; Miyaki 2011; Pandejpong 2012; Radonovich 2019; Ram 2015; Simmerman 2011; Suess 2012; Turner 2012; Yeung 2011; Zomer 2015). Seven studies did not report sufficient information on incomplete data (attrition bias) (Aelami 2015; DiVita 2011; Feldman 2016; Hartinger 2016; Ibfelt 2015; McConeghy 2017; Priest 2014). Twelve studies had a high risk of attrition bias (Azor‐Martinez 2016; Ban 2015; Biswas 2019; Huda 2012; Little 2015; Millar 2016; Najnin 2019; Nicholson 2014; Savolainen‐Kopra 2012; Stebbins 2011; Talaat 2011; Temime 2018). In Azor‐Martinez 2016, attrition levels were high and differed between the two groups. Ban 2015 did not report on reasons for loss to follow‐up. Biswas 2019 did not provide information on missing participants (28 children in the control schools and two children in the intervention schools). Huda 2012 did not provide a flow diagram of study participants. Little 2015 had high attrition that differed between the two groups. Attrition in Millar 2016 differed amongst the three groups. In addition, ARI cases were captured utilising clinic‐based medical records for those participants who sought hospital care only. In Najnin 2019, there was high migration movement during the study, which could have distorted the baseline characteristics even more. There was no description of how such migration and changes in the intervention group were dealt with. In Nicholson 2014, households were removed from the study if they provided no data for five consecutive weeks. Although attrition was reported in Savolainen‐Kopra 2012, and 76% of volunteers who were recruited at the beginning of the reporting period completed the study, new recruits were added during the study to replace volunteers lost in most clusters. The total number of reporting participants at the end of the trial was 626 (91.7%) compared to the beginning, meaning that 15.7% of participants were replaced during the study. In Stebbins 2011,reasons for episodes of absence in 66% of the study participants were not reported. Talaat 2011 did not provide a flow chart of clusters flow during the study period and provided no information on withdrawal. Temime 2018 was greatly biased due to underreporting of outcomes in the control groups. Furthermore, no study flow chart was provided, and there was no reporting on any exclusions.

Selective reporting

For this 2022 review update, six of the 11 newly included studies reported all specified outcomes and were judged to have a low risk of selective reporting (Ashraf 2020; Bundgaard 2021; Fretheim 2022a; Gutiérrez‐García 2022; Helsingen 2021; Young 2021). Three studies had no published protocol and were considered to have an unclear risk of selective reporting (Alfelali 2020; Almanza‐Reyes 2021; Teesing 2021). The remaining two new included studies are considered to have a high risk of bias in this domain. Abaluck 2022 did not report on prespecified seroconversion, while in Swarthout 2020, none of the outcomes reported were prespecified in the trial registry.

In the 2020 review, 22 included studies reported all specified outcomes and were judged as at low risk of reporting bias (Aiello 2012; Barasheed 2014; Canini 2010; Chard 2019; Goodall 2014; Hartinger 2016; Ibfelt 2015; Ide 2016; Little 2015; MacIntyre 2011; MacIntyre 2013; MacIntyre 2015; MacIntyre 2016; Pandejpong 2012; Priest 2014; Radonovich 2019; Savolainen‐Kopra 2012; Simmerman 2011; Suess 2012; Temime 2018; Turner 2012; Zomer 2015). For 18 studies, it is unlikely that other outcomes were measured and not reported, although no protocol was available to assess reporting bias (Aelami 2015; Alzaher 2018; Arbogast 2016; Azor‐Martinez 2016; Azor‐Martinez 2018; Ban 2015; Biswas 2019; Correa 2012; DiVita 2011; Feldman 2016; Hubner 2010; Huda 2012; Ide 2014; Miyaki 2011; Nicholson 2014; Stebbins 2011; Talaat 2011; Yeung 2011). Three studies were at high risk of reporting bias (McConeghy 2017; Millar 2016; Najnin 2019). In McConeghy 2017, URTI was mentioned in the methods (the intervention presumably would have targeted these), but only lower respiratory tract infection (LRTI) and overall infection were reported. Millar 2016 was originally conducted for another purpose; we could not find the respiratory outcomes reported in the study as part of the original study protocol. In Najnin 2019, the published study protocol did not include respiratory illness as an outcome.

Other potential sources of bias

An additional consideration for cluster‐RCTs is identification/recruitment bias, where individuals are recruited in the trial after clusters are randomised. Such bias can introduce an imbalance amongst groups.

In this 2022 review, of the six cluster‐RCTs included, we judged four to have a low risk of identification/recruitment bias (Abaluck 2022; Ashraf 2020; Swarthout 2020; Teesing 2021). In Abaluck 2022, all of people in the village were assigned to one study arm (control, cloth mask or surgical mask villages). In Ashraf 2020, participants were unaware of their intervention group assignment until after the baseline survey and randomisation. In Swarthout 2020, village clusters comprised of 12 enrolled households, while in Teesing 2021 randomisation was done per nursing home. Alfelali 2020 recruited individuals after cluster‐randomisation and is judged to have a high risk of recruitment bias, while in Young 2021, participation of students and staff contacts were made after random assignment of the school through written consent or electronic completion of a consent form.

Of the cluster‐RCTs included in our 2020 review, we judged 13 to have a low risk of identification/recruitment bias (Arbogast 2016; Biswas 2019; Canini 2010; Cowling 2008; Longini 1988; Luby 2005; MacIntyre 2015; MacIntyre 2016; Roberts 2000; Sandora 2005; Suess 2012; Temime 2018; White 2001). In Arbogast 2016, all identified individuals (office workers) were included in the assigned cluster. Schools were identified and then randomised to the clusters; students were then randomly selected from each classroom and school. Nine studies described the identification of participants, consenting/enrolling, and then randomising to the clusters (Canini 2010; Cowling 2008; Longini 1988; Luby 2005; MacIntyre 2015; MacIntyre 2016; Roberts 2000; Sandora 2005; White 2001). Suess 2012 identified and consented patients, then recruitment was performed by physicians unaware of cluster assignment. In Temime 2018, directors of the included nursing homes agreed to participate in the study before randomisation, and written consent was not required from the residents.

Amongst the newly included studies, we judged four cluster‐RCTs as at low risk of identification/recruitment bias (Abaluck 2022; Swarthout 2020; Teesing 2021; Young 2021). In Abaluck 2022, the village was the unit of randomisation and all households received one arm of the study (control, surgical mask or cloth mask). In Swarthout 2020, village clusters were each randomised by blocks (group of nine adjacent clusters) into eight groups. In Teesing 2021 nursing homes were computer randomised after baseline hand hygiene measurements to either the intervention arm or the control arm. In Young 2021, schools were randomly assigned (1:1) to either a policy of offering contacts daily testing over seven days to allow continued school attendance (intervention group) or to follow the usual policy of isolation of contacts for 10 days (control group). In two studies there were insufficient details to permit a judgement of the risk of bias (Alfelali 2020; Ashraf 2020).

In the 2020 review, we judged 11 cluster‐RCTs as at high risk of identification/recruitment bias (Aiello 2010; Aiello 2012; Azor‐Martinez 2018; Chard 2019; Correa 2012; Cowling 2009; Larson 2010; McConeghy 2017; Nicholson 2014; Priest 2014; Savolainen‐Kopra 2012). In Aiello 2010 and Aiello 2012, recruitment continued for two weeks after the start of the study, which could have introduced bias. Six trials identified and recruited participants after cluster randomisation (Azor‐Martinez 2018; Chard 2019; Cowling 2009; Larson 2010; McConeghy 2017; Nicholson 2014). Three trials recruited new participants after the start of the study to replace those lost to follow‐up (Correa 2012; Priest 2014; Savolainen‐Kopra 2012). We judged five cluster‐RCTs to have probable identification/recruitment bias (Alzaher 2018; Barasheed 2014; MacIntyre 2011; Najnin 2019; Radonovich 2019), whereas in 19 studies there were insufficient details to permit a judgement of risk of bias (Carabin 1999; DiVita 2011; Feldman 2016; Hartinger 2016; Huda 2012; Ibfelt 2015; Kotch 1994; Ladegaard 1999; MacIntyre 2009; MacIntyre 2013; Millar 2016; Miyaki 2011; Pandejpong 2012; Radonovich 2019; Sandora 2008; Stebbins 2011; Talaat 2011; Yeung 2011; Zomer 2015).

Two of the newly included cluster‐RCTs reported intracluster correlation coefficient (ICC) to adjust sample size, taking into consideration clustering effects, and described adjusting outcomes for clustering effect using different statistical methods, or provided justification for not performing adjusted analysis for clustering (Alfelali 2020; Swarthout 2020). For four studies there were insufficient details to permit a judgement of risk of bias (Abaluck 2022; Ashraf 2020; Teesing 2021; Young 2021) since they provided insufficient details on ICC and/or did not perform adjusted analysis or justified the absence of it.

Twenty‐six cluster‐RCTs identified in the 2020 review reported intracluster correlation coefficient (ICC) to adjust sample size, taking into consideration clustering effects, and described adjusting outcomes for clustering effect using different statistical methods, or provided justification for not performing adjusted analysis for clustering (Aiello 2010; Aiello 2012; Arbogast 2016; Canini 2010; Carabin 1999; Correa 2012; Cowling 2008; Cowling 2009; Hartinger 2016; Huda 2012; Little 2015; Luby 2005; MacIntyre 2009; MacIntyre 2011; MacIntyre 2013; MacIntyre 2015; MacIntyre 2016; McConeghy 2017; Priest 2014; Radonovich 2019; Ram 2015; Roberts 2000; Stebbins 2011; Suess 2012; Talaat 2011; Temime 2018). Five cluster‐RCTs did not report the ICC but described adjusting outcomes for clustering effect using different statistical methods, or explained why adjusted analysis for clustering was not performed (Biswas 2019; Chard 2019; McConeghy 2017; Simmerman 2011; Zomer 2015). Thirteen cluster‐RCTs provided insufficient details on ICC and/or did not perform adjusted analysis or justified the absence of it (Alzaher 2018; Azor‐Martinez 2016; Azor‐Martinez 2018; Barasheed 2014; Feldman 2016; Larson 2010; Millar 2016; Miyaki 2011; Najnin 2019; Nicholson 2014; Pandejpong 2012; Savolainen‐Kopra 2012; Yeung 2011). Two cluster‐RCTs reported the ICC but did not perform adjusted analysis or justified the absence of it (Sandora 2005; Sandora 2008).

Effects of interventions

See: Table 1; Table 2; Table 3

Comparison 1: Medical/surgical masks compared to no masks

We included 12 trials (10 of which were cluster‐RCTs) comparing medical/surgical masks versus no masks (Abaluck 2022; Alfelali 2020; Aiello 2012; Barasheed 2014; Bundgaard 2021; Canini 2010; Cowling 2008; Jacobs 2009; MacIntyre 2009; MacIntyre 2015; MacIntyre 2016; Suess 2012). Two trials were conducted with healthcare workers (HCWs) (Jacobs 2009; MacIntyre 2015), whilst the other 10 studies included people living in the community. In the acute care hospital setting, as opposed to the community setting, variable mask use occurred, according to usual practices in the settings where the studies were undertaken, varying from just under 16% most of the time to 23.6% wearing for > 70% of all working hours (Jacobs 2009; MacIntyre 2015). We therefore excluded the two studies in the acute care hospital setting from the meta‐analysis, and report results from these studies narratively. Ten trials were conducted in non‐pandemic settings, and two were conducted during the SARS‐CoV‐2 pandemic (Abaluck 2022; Bundgaard 2021).

Primary outcomes

1. Numbers of cases of viral respiratory illness

Influenza/COVID‐like illness

Pooling of nine trials conducted in the community found an estimate of effect for the outcomes of influenza/COVID‐like illness cases (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; 9 trials; 276,917 participants; moderate‐certainty evidence; Analysis 1.1) suggesting that wearing a medical/surgical mask will probably make little or no difference for this outcome. Two studies in healthcare workers provided inconclusive results with very wide confidence intervals: RR 0.88, 95% CI 0.02 to 32; and RR 0.26, 95% CI 0.03 to 2.51, respectively (Jacobs 2009; MacIntyre 2015).

Laboratory‐confirmed influenza/SARS‐CoV‐2 cases

Similarly, the estimate of effect for laboratory‐confirmed influenza/SARS‐CoV‐2 cases (RR 1.01, 95% CI 0.72 to 1.42; 6 trials, 13,919 participants; moderate‐certainty evidence; Analysis 1.1) suggests that wearing a medical/surgical mask probably makes little or no difference compared to not wearing a mask for this outcome.

Laboratory‐confirmed other respiratory viruses

One community study reported on laboratory‐confirmed other respiratory viruses, showing RR 0.58, 95% CI 0.25 to 1.31; Analysis 1.1, and another study in healthcare workers reported RR 0.79, 95% CI 0.42 to 1.52 (MacIntyre 2015).

Assessing both source control and personal protection

The design of most trials assessed whether masks protected the wearer. Six trials were cluster‐RCTs, with all participants in the intervention clusters required to wear masks, thus assessing both source control and personal protection. In two trials the clusters were households with a member with new influenza; neither of these studies found any protective effect (RR 1.03 in 105 households (Canini 2010); RR 1.21 in 145 households (MacIntyre 2009)). In two trials the clusters were college dormitories during the influenza season; neither study found any reduction (RR 1.10 in 37 dormitories (Aiello 2012); RR 0.90 in three dormitories (Aiello 2010)).

Studies conducted during the SARS‐CoV‐2 pandemic

Two studies were conducted during the SARS‐CoV‐2 pandemic (Abaluck 2022; Bundgaard 2021), with the former being a very large cluster‐RCT of villages in Bangledesh and the latter a large RCT conducted in Denmark.

Exclusion of study due to insufficient number of clusters

We excluded Aiello 2010 from the meta‐analysis since we did not consider 'randomisation' of three clusters to three arms to be a proper randomised trial.

2. Adverse events related to the intervention

Canini 2010 reported that 38 (75%) of participants in the intervention arm experienced discomfort with the mask use due to warmth (45%), respiratory difficulties (33%), and humidity (33%). Children reported feeling pain more frequently (3/12) than other participants wearing adult face masks (1/39; P = 0.04). In MacIntyre 2015, adverse events associated with face mask use were reported in 40.4% (227/562) of HCWs in the medical‐mask arm. General discomfort (35.1%; 397/1130) and breathing problems (18.3%; 207/1130) were the most frequently reported adverse events. Suess 2012 reported that the majority of participants (107/172; 62%) did not report any problems with mask‐wearing. More adults reported no problems (71%) compared to children (36/72; 50%; P = 0.005). The main issues when wearing a face mask for adults as well as for children were "heat/humidity" (18/34; 53% of children; 10/29; 35% of adults; P = 0.1), followed by "pain" and "shortness of breath". Alfelali 2020 reported the most common side effects of wearing a mask in Hajj pilgrims were difficulty in breathing (26%) and discomfort (22%). Although no details were provided, Bundgaard 2021 mentioned that 14% of participants had adverse reactions. Cowling 2008 and Abaluck 2022 mentioned that no adverse events were reported. The other trials did not report measuring adverse outcomes.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Jacobs 2009 reported that participants in the mask group were significantly more likely to experience more days with headache and feeling bad. They found no significant differences between the two groups for symptom severity scores. None of the other trials reported this outcome.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 2: N95/P2 respirators compared to medical/surgical masks

We included five trials comparing medical/surgical masks with N95/P2 respirators (Loeb 2009; MacIntyre 2009; MacIntyre 2011; MacIntyre 2013; Radonovich 2019). All of these trials except MacIntyre 2009 included HCWs. MacIntyre 2009 included carers and household members of children with a respiratory illness recruited from a paediatric outpatient department and a paediatric primary care practice in Sydney, Australia. None of the trials were conducted during the SARS‐CoV‐2 pandemic.

Primary outcomes

1. Numbers of cases of viral respiratory illness

Clinical respiratory illness

Pooling of three trials found an estimate of effect suggesting considerable uncertainty as to whether an N95/P2 respirator provides any benefit compared to medical/surgical masks for the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; 7799 participants, very low‐certainty evidence; Analysis 2.1) (MacIntyre 2011; MacIntyre 2013 (two arms); Radonovich 2019).

Influenza‐like‐illness

Based on five trials conducted in four healthcare settings and one household, the estimates of effect for the outcome of ILI (RR 0.82, 95% CI 0.66 to 1.03; 8407 participants, low‐certainty evidence; Analysis 2.1) suggest that N95/P2 respirators may make little or no difference for this outcome (Loeb 2009; MacIntyre 2009; MacIntyre 2011; MacIntyre 2013; Radonovich 2019).

Laboratory‐confirmed influenza

The estimate of the effect for the outcome of laboratory‐confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; 8407 participants, moderate‐certainty evidence; Analysis 2.1) suggests that the use of a N95/P2 respirator compared to a medical/surgical mask probably makes little or no difference for this more precise and objective outcome.

The outcomes clinical respiratory illness and ILI were reported separately. Considering how these outcomes were defined, it is highly likely that there was considerable overlap between the two, therefore these outcomes were not combined into a single clinical outcome (Analysis 2.1). The laboratory‐confirmed viral respiratory infection outcome included influenza primarily but multiple other common viral respiratory pathogens were also included in several studies. The laboratory‐confirmed viral infection outcome was considered more precise and objective in comparison to the clinical outcomes, which were more subjective and considered to be less precise. The findings did not change when we restricted the evidence to HCWs (Analysis 2.2).

2. Adverse events related to the intervention

Harms were poorly reported, but generally discomfort wearing medical/surgical masks and N95/P32 respirators was mentioned in several studies. Radonovich 2019 mentioned that participants wearing the N95 respirator reported skin irritation and worsening of acne. MacIntyre 2011 reported that adverse events were more common with N95 respirators; in particular, discomfort was reported in 41.9% of N95 wearers versus 9.8% of medical‐mask wearers (P < 0.01); headaches were more common with N95 (13.4% versus 3.9%; P < 0.01); difficulty breathing was reported more often in the N95 group (19.4% versus 12.5%; P = 0.01); and N95 caused more problems with pressure on the nose (52.2% versus 11.0%; P < 0.01). In MacIntyre 2013, fewer participants using the N95 respirator reported problems (38% (195/512) versus 48% (274/571) of participants in the medical‐mask arm; P = 0.001). Loeb 2009 mentioned that no adverse events were reported.

The one trial conducted in the community mentioned that more than 50% of participants reported concerns with both types of masks, mainly that wearing them was uncomfortable, but there were no significant differences between the P2 (N95) and surgical‐mask groups (MacIntyre 2009).

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Loeb 2009 reported that 42 participants (19.8%) in the surgical‐mask group reported an episode of work‐related absenteeism compared with 39 (18.6%) of participants in the N95 respiratory group (absolute risk difference −1.24%, 95% CI −8.75% to 6.27%; P = 0.75).

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Loeb 2009 reported that there were no episodes of LRTIs.

Comparison 3: Hand hygiene compared to control

Nineteen trials compared hand hygiene interventions with control and provided sufficient data to include in meta‐analyses (Ashraf 2020; Azor‐Martinez 2018; Biswas 2019; Correa 2012; Cowling 2008; Cowling 2009; Hubner 2010; Larson 2010; Little 2015; Millar 2016; Nicholson 2014; Ram 2015; Roberts 2000; Sandora 2005; Simmerman 2011; Stebbins 2011; Swarthout 2020; Teesing 2021; Zomer 2015). The populations of these studies included adults, children, and families, in settings such as schools, childcare centres, homes, and offices. None of the studies was conducted during a pandemic, although a few studies were conducted during peak influenza seasons. A further 16 trials comparing hand hygiene to a control had other outcomes or insufficient information to include in meta‐analyses (Alzaher 2018; Arbogast 2016; Azor‐Martinez 2016; DiVita 2011; Feldman 2016; Gwaltney 1980; Ladegaard 1999; Luby 2005; Morton 2004; Priest 2014; Savolainen‐Kopra 2012; Talaat 2011; Temime 2018; Turner 2012; White 2001; Yeung 2011). The results of these trials were consistent with the findings of our meta‐analyses. The results for all outcomes from the 19 trials that were meta‐analysed and the 16 trials that were not meta‐analysed are shown in Table 5.

2 Results from trials of hand hygiene compared to control
StudyComparison (see Table 4 for details of interventions)Reported outcomesResults
Alzaher 2018cluster‐RCTSaudi ArabiaHand‐washing workshop and posters versus usual practice% absence days due to URI0.39% and 0.72% in intervention group schools; 0.86% and 1.39% in control schools
Arbogast 2016cluster‐RCTUSAHand sanitiser + wipes + hand foam versus noneBoth groups received education + signage about hand‐washing1. Health insurance claims for preventable illnesses per employee2. Absences per employee1. 0.30 claims in intervention; 0.37 in control (27% relative reduction; P = 0.03)2. 1.45 in intervention; 1.53 in control (5.0% relative reduction in intervention; P = 0.30)
Ashraf 2020 cluster‐RCTBangladesh6 intervention arms: water quality, sanitation, hand washing, combined WSH, nutrition, nutrition + WSH7‐day prevalence of acute respiratory illness (ARI). Hand washing reduced ARI cases by 32% (RR 0.68, 95% CI 0.52 to 0.88)
Azor‐Martinez 2016RCTSpainHand‐washing with soap and water plus hand sanitiser versus usual hand‐washing practices% absence days due to URI1.15% in intervention; 1.68% in control. Significantly lower in intervention (P < 0.001)
Azor‐Martinez 2018cluster‐RCTSpain Education and hand hygiene with soap and water versus hand hygiene with sanitiser versus usual hand‐washing procedures1. URI incidence rate ratio (primary)2. Percentage difference in absenteeism days1. HH soap versus control 0.94 (95% CI 0.82 to 1.08); HH sanitiser versus control 0.77 (95% CI 0.68 to 0.88); HH soap versus HH sanitiser 1.21 (95% CI 1.06 to 1.39)2. HH soap 3.9% versus control 4.2% (P < 0.001); HH sanitiser 3.25% versus control 4.2% (P = 0.026); HH soap 3.9% versus HH sanitiser 3.25% (P < 0.001)
Biswas 2019cluster‐RCTBangladeshHand sanitiser and respiratory hygiene education and cough/sneeze hygiene versus no intervention1. ILI incidence rate (at least 1 episode)2. Laboratory‐confirmed influenza1. 22 per 1000 student‐weeks in intervention; 27 per 1000 student‐weeks in control, not statistically significantly different2. 3 per 1000 student‐weeks in intervention; 6 per 1000 student‐weeks in control, P = 0.01
Correa 2012cluster‐RCTColombiaAlcohol‐based hand sanitiser in addition to hand‐washing versus usual hand‐washing practice ARIs in 3rd trimester of follow‐upHazard ratio for intervention to control 0.69 (95% CI 0.57 to 0.83)
Cowling 2008cluster‐RCTHong Kong
 Hand hygiene (36 households) versus face mask (mask) versus education (control)Secondary attack rate for:1. laboratory‐confirmed influenza;2. ILI definition 1;3. ILI definition 2;4. ILI definition 3.1. HH 0.06; mask 0.07; control 0.062. HH 0.18; mask 0.18; control 0.183. HH 0.11; mask 0.10; control 0.114. HH 0.04; mask 0.08; control 0.04 
Cowling 2009cluster‐RCTHong Kong Hand hygiene (HH) versus face mask + hand hygiene (HH + mask) versus education (control)Secondary attack rate for:1. laboratory‐confirmed influenza;2. ILI definition 1;3. ILI definition 2.1. HH 5; HH + mask 7; control 102. HH 16; HH + mask 21; control 193. HH 4; HH + mask 7; control 5
DiVita 2011 (conference abstract)RCTBangladeshHand‐washing stations with soap and motivation vs none1. SAR for laboratory‐confirmed influenza2. SAR for ILI1. SAR higher in intervention group (11.0% versus 7.5%)2. SAR higher in intervention group (14.2% versus 11.9%)
Feldman 2016cluster‐RCTIsraelHand disinfection + soap and water installed versus none1. Number of respiratory infections2. Number of off‐duty days1. 11 in each group2. 112 in intervention; 104 in control
Gwaltney 1980
RCTUSAVirucidal hand wash versus placebo1. Number with illness after immediate exposure2. Number with illness after 2‐hour delay in exposure1. 0 of 8 in intervention; 7 of 7 in control2. 1 of 10 in intervention; 6 of 10 in control
Hubner 2010RCTGermanyHand disinfection provided versus noneOdds ratios (95% CI) (intervention:control)1. Influenza2. Common cold3. Sinusitis4. Sore throat5. Fever6. Cough1. 1.02 (0.20 to 5.23)2. 0.35 (0.17 to 0.71)3. 1.87 (0.52 to 6.74)4. 0.62 (0.31 to 1.25)5. 0.38 (0.14 to 0.99)6. 0.45 (0.22 to 0.91)
Ladegaard 1999RCTDenmarkHand hygiene and education versus noneSick days during the "effect period"22 days/child in the intervention group versus 36 days/child in the control group
Larson 2010cluster‐RCTUSAEducation versus education with alcohol‐based hand sanitiser versus education with hand sanitiser and face masks  Incidence rate ratios (episodes per 1000 person‐weeks) for:
1. URI;
2. ILI;
3. influenza.Secondary attack rates for:
4. URI/ILI/influenza;
5. ILI/influenza.1. HS 29; HS + masks 39; control 352. HS 1.9; HS + masks 1.6; control 2.33. HS 0.6; HS + masks 0.5; control 2.34. HS 0.14; HS + masks 0.12; control 0.145. HS 0.02; HS + masks 0.02; control 0.02
Little 2015RCTEnglandBespoke automated web‐based hand hygiene motivational intervention with tailored feedback versus noneNumber of participants with 1 or more episodes of URIRisk ratio for intervention to control 0.86 (95% CI 0.83 to 0.89; P < 0.001)
Luby 2005RCTPakistanAntibacterial soap and education about hand‐washing versus plain soap and education versus none1. Cough or difficulty breathing in children < 15 yrs (episodes/100 person‐weeks)2. Congestion or coryza in children < 15 yrs (episodes/100 person‐weeks)3. Pneumonia in children < 5 yrs (episodes/100 person‐weeks)All outcomes significantly lower than control1. 4.21 in antibacterial soap group; 4.16 in plain soap group; 8.50 in control group2. 7.32 in antibacterial soap group; 6.87 in plain soap group; 14.78 in control group3. 2.42 in antibacterial soap group; 2.20 in plain soap group; 4.40 in control group
Millar 2016
cluster‐RCTUSAStandard educational promotion of hand‐washing versus enhanced promotion versus promotion plus a once‐weekly application of chlorhexidine‐based body washIncidence rates of ARI over 20 months37.7 enhanced + body wash; 29.3 enhanced; 35.3 standard; RR for enhanced + body wash to standard 1.07 (95% CI 1.03 to 1.11); RR for enhanced to enhanced + body wash 0.78 (95% CI 0.75 to 0.81)
Morton 2004cluster‐RCTcross‐over studyUSAAlcohol gel plus education versus regular hand‐washingAbsence due to infectious illnessResults not stated numerically
Nicholson 2014cluster‐RCTIndiaCombination hand‐washing promotion with provision of free soap versus noneTarget children:
1. Episodes of ARI (per 100 person‐weeks)
2. School absence episodes (per 100 person‐days)Families:
3. Episodes of ARI1. 16 in intervention; 19 in control2. 1.2 in intervention; 1.7 in control3. 10 in intervention; 11 in control
Priest 2014cluster‐RCTNew ZealandHand hygiene education and hand sanitiser versus education alone1. % absence days due to respiratory illness2. % absence days due to any illness1. 0.84% in intervention group; 0.80% in control (P = 0.44)2. 1.21% in intervention group; 1.16% in control (P = 0.35)
Ram 2015RCTBangladeshEducation to promote intensive hand‐washing in households plus soap provision versus none1. Secondary attack ratio for intervention to control for ILI2. Laboratory‐confirmed influenza1. 1.24 (95% CI 0.93 to 1.65)2. 2.40 (95% CI 0.68 to 8.47)
Roberts 2000cluster‐RCTAustraliaHand‐washing programme with training for staff and children versus noneIncidence rate ratio for ARIIRR 0.92 for intervention to control (95% CI 0.86 to 0.99)
Sandora 2008
cluster‐RCTUSAHand sanitiser and education versus noneIncidence rates for ARI (episodes per person‐month)0.43 in intervention; 0.42 in control
Savolainen‐Kopra 2012cluster‐RCTFinlandHand hygiene with soap and water (IR1 group) versus with alcohol‐based hand rub (IR2 group) versus control (none); intervention groups also received education1. Number of respiratory infection episodes/week2. Number of reported infection episodes/week3. Number of reported sick leave episodes/week1. 0.076 in IR1; 0.085 in IR2; 0.080 in control, NS2. 0.097 in IR1; 0.107 in IR2; 0.104 in control, NS3. 0.042 in IR1; 0.035 in IR2; 0.035 in control. Significantly higher in IR1 compared with control
Simmerman 2011cluster‐RCTThailandHand‐washing (HW) versus handwashing plus paper surgical face masks (HW + FM) versus control (none)Odds ratios for secondary attack rates for influenzaOR for HW: control 1.20 (95% CI 0.76 to 1.88)OR for HW + masks: control 1.16 (95% CI 0.74 to 1.82)OR for HW + masks: HW 0.72 (95% CI 0.21 to 2.48)
Stebbins 2011
cluster‐RCTUSATraining in hand and respiratory (cough) hygiene + hand sanitiser versus noneIncidence rate ratios for intervention to control for:
1. laboratory‐confirmed influenza (RT‐PCR);
2. influenza‐A;
3. absence.1. IRR 0.81 (95% CI 0.54 to 1.23)2. IRR 0.48 (95% CI 0.26 to 0.87)3. IRR 0.74 (95% CI 0.56 to 0.97)
Swarthout 2020 cluster‐RCTKenyaThere were 6 intervention groups: chlorinated drinking water (W), improved sanitation (S), handwashing with soap (H), combined WSH, improved nutrition (N) through counselling lipid based nutrient supplementation (LNS) combined WSHN There were 2 control groups passive control (no promotional visits), a double‐sized active control (monthly visits to measure mid–upper arm circumference)Prevalence of ARIs in childrenNo evidence of an effect: RR 0.97, 95% CI 0.90 to 1.04.
Talaat 2011cluster‐RCTEgyptMandatory hand‐washing intervention + education versus none1. Number of absence days due to ILI2. Number of absence days1. 917 in intervention; 1671 in control (P < 0.001)2. 13,247 in intervention; 19,094 in control (P < 0.001)
Teesing 2021cluster‐RCTNetherlandsHand hygiene enhancement activities versus no activities. Incidence of gastroenteritis, influenza‐like illness (ILI), assumed pneumonia, urinary tract infections (UTIs), and infections caused MRSA in residentsHand hygiene reduced risk of ILI (RR 0.51, 95% CI 0.31 to 0.83)
Temime 2018cluster‐RCTFranceHand hygiene with alcohol‐based hand rub, promotion, staff education, and local work groups versus noneIncidence rate of ARI clusters (5 or more people in same nursing home)2 ARI clusters in intervention; 1 in control
Turner 2012RCTUSAAntiviral hand treatment versus no treatment1. Number of rhinovirus infections2. Common cold infections3. Rhinovirus‐associated illnesses1. 49 in intervention; 49 in control, NS2. 56 in intervention; 72 in control, NS3. 26 in intervention; 24 in control, NS
White 2001DB‐RCTUSA Hand rub with benzalkonium chloride (hand sanitiser) versus placeboARI symptomsLaboratory: testing of virucidal and bactericidal activity of the product30% to 38% decrease of illness and absenteeism (RR for illness absence incidence 0.69; RR for absence duration 0.71)
Yeung 2011cluster‐RCTHong KongAlcohol‐based hand gel + materials + education versus control (basic life support workshop)Difference between pre‐study period and post study in pneumonia infections recorded in residents0.63/1000 reduction in intervention group; 0.16/1000 increase in control
Zomer 2015
cluster‐RCTNetherlands4 components:
1. Hand hygiene products, paper towel dispensers, soap, alcohol‐based hand sanitiser, and hand cream provided for 6 months2. Training and booklet3. 2 team training sessions aimed at hand hygiene improvement4. Posters and stickers for caregivers and children as reminders.Combination versus usual practiceIncidence rate ratio for intervention to control for common cold IRR 1.07 (95% CI 0.97 to 1.19)8.2 episodes per child‐year in intervention; 7.4 episodes per child‐year in control

Primary outcomes

1. Numbers of cases of viral respiratory illness

Acute respiratory infection (ARI)

Pooling of nine trials for the broad outcome of ARI showed a 14% relative reduction in the numbers of participants with ARI (RR 0.86, 95% CI 0.81 to 0.90; 52,105 participants, moderate‐certainty evidence; Analysis 3.1.1) in the hand hygiene group (Analysis 3.1), suggesting a probable benefit (Ashraf 2020; Azor‐Martinez 2018; Correa 2012; Larson 2010; Little 2015; Millar 2016; Nicholson 2014; Sandora 2005; Swarthout 2020).

Influenza‐like‐illness (ILI) and laboratory‐confirmed influenza

When considering the more strictly defined outcomes of ILI (Biswas 2019; Cowling 2008; Cowling 2009; Hubner 2010; Larson 2010; Little 2015; Ram 2015; Roberts 2000; Simmerman 2011; Teesing 2021; Zomer 2015), and laboratory‐confirmed influenza (Biswas 2019; Cowling 2008; Cowling 2009; Hubner 2010; Larson 2010; Ram 2015; Simmerman 2011; Stebbins 2011) the estimates of the effect were heterogeneous, suggesting that hand hygiene may make little or no difference (RR 0.94, 95% CI 0.81 to 1.09 for ILI; 34,503 participants, low‐certainty evidence; Analysis 3.1.2); (RR 0.91, 95% CI 0.63 to 1.30 for laboratory‐confirmed influenza; 8332 participants; low‐certainty evidence; Analysis 3.1.3).

Composite outcome ‘ARI or ILI or influenza'

All 19 trials could be pooled for analysis of the composite outcome ‘ARI or ILI or influenza’, with each study only contributing once with the most comprehensive outcome (in terms of number of events) reported showing an 11% relative reduction in participants with a respiratory illness, suggesting that hand hygiene may offer a benefit (RR 0.89, 95% CI 0.83 to 0.94; low‐certainty evidence; Analysis 3.2), but with high heterogeneity. A funnel plot of the 19 trial results did not appear to suggest any small study effects for this outcome (Figure 4).

4 (Figure not reproduced here; see the original article.)

Sensitivity analysis

In a sensitivity analysis we used only the most precise and unequivocal (with laboratory confirmed considered the most precise and an undefined ARI considered the least precise) outcome reported in each of 12 studies identified by JMC, an infectious disease physician, and found an estimate of effect in favour of hand hygiene, but with wider CIs (RR 0.88, 95% CI 0.77 to 1.02; Analysis 3.3).

Subgroup analysis by age group

We considered that studies in children might have a different effect than studies in adults, so we conducted subgroup analysis by age group. We found no evidence of a difference in treatment effect by age group (P = 0.18; Analysis 3.4).

2. Adverse events related to the intervention

Correa 2012 reported that no adverse events were observed; in the study by Priest 2014, skin reaction was recorded for 10.4% of participants in the hand sanitiser group versus 10.3% in the control group (RR 1.01, 95% CI 0.78 to 1.30).

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Three trials measured absenteeism from school or work and demonstrated a 36% relative reduction in the numbers of participants with absence in the hand hygiene group (RR 0.64, 95% CI 0.58 to 0.71; Analysis 3.5) (Azor‐Martinez 2016; Hubner 2010; Nicholson 2014).

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 4: Hand hygiene + medical/surgical masks compared to control

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza)

Six trials (Aelami 2015; Aiello 2012; Cowling 2009; Larson 2010; Simmerman 2011; Suess 2012) were able to be pooled to compare the use of the combination of hand hygiene and medical/surgical masks with control. Four of these trials were in households, two in university student residences, and one at the annual Hajj pilgrimage. For the outcomes ILI and laboratory‐confirmed influenza, pooling demonstrated an estimate of effect suggesting little or no difference between the hand hygiene and medical/surgical mask combination and control. The number of trials and events was lower than for comparisons of hand hygiene alone, or medical/surgical masks alone, and the confidence interval was wide. For ILI, the RR for intervention compared to control was 1.03 (95% CI 0.77 to 1.37; 4504 participants; Analysis 4.1.1), and for influenza it was 0.97 (95% CI 0.69 to 1.36; 3121 participants; Analysis 4.1.2). Full results of these trials are shown in Table 6

3 Results from trials of hand hygiene + medical/surgical masks compared to control
StudyComparison (see Table 4 for details of interventions)Reported outcomesResults
Aelami 2015 (conference abstract)RCTSaudi ArabiaHand hygiene education + alcohol‐based hand rub + soap + surgical masks vs noneProportion with ILI (defined as presence of ≥ 2 of the following during their stay: fever, cough, and sore throat)52% in intervention; 55.3% in control (P < 0.001)
Aiello 2010cluster‐RCTUSAFace mask use (FM) vs face masks + hand hygiene (FM + HH) vs controlNote that this study is not included in meta‐analysis as each treatment group included only 1 cluster.1. ILI
2. Laboratory‐confirmed influenza A or BSignificant reduction in ILI cases in both intervention groups compared with control over weeks 3 to 6
No significant differences between FM and FM + HH
Aiello 2012cluster‐RCTUSAFace mask use (FM) vs face masks + hand hygiene (FM + HH) vs control1. Clinical ILI
2. Laboratory‐confirmed influenza A or B1. Non‐significant reductions in FM group compared with control over all weeks. Significant reduction in FM + HH group compared with control in weeks 3 to 62. Non‐significant reductions in both intervention groups compared with control
Cowling 2009cluster‐RCTHong KongHand hygiene (HH) vs hand hygiene plus face masks (HH + mask) vs controlSecondary attack ratio for:
1. laboratory‐confirmed influenza;
2. ILI definition 1;
3. ILI definition 2.1. HH 5; HH + mask 7; control 10
2. HH 16; HH + mask 21; control 19
3. HH 4; HH + mask 7; control 5
Larson 2010cluster‐RCTUSAEducation (control) vs education with alcohol‐based hand sanitiser (HS) vs education + HS + face masks (HS + mask)Incidence rate ratios (episodes per 1000 person‐weeks) for:
1. URI;
2. ILI;
3. influenza.Secondary attack rates for:
4. URI/ILI/influenza;
5. ILI/influenza.1. HS 29; HS + mask 39; control 35
2. HS 1.9; HS + mask 1.6; control 2.3
3. HS 0.6; HS + mask 0.5; control 2.3
4. HS 0.14; HS + mask 0.12; control 0.14
5. HS 0.02; HS + mask 0.02; control 0.02
Simmerman 2011cluster‐RCTThailandControl vs hand‐washing (HW) vs hand‐washing + paper surgical face masks (HW + mask)Odds ratio for secondary attack rates for influenzaOR for HW: control 1.20 (95% CI 0.76 to 1.88)
OR for HW + mask: control 1.16 (95% CI 0.74 to 1.82)
OR for HW + mask: HW 0.72 (95% CI 0.21 to 2.48)
Suess 2012cluster‐RCTGermanyFace mask + hand hygiene (mask + HH) vs face masks only (mask) vs none (control)Secondary attack rates in household contacts:
1. Laboratory‐confirmed influenza
2. ILI1. Mask 9; mask + HH 15; control 23
2. Mask 9; mask + HH 9; control 17

2. Adverse events related to the intervention

Adverse events related to mask wearing in the study by Suess 2012 are reported under Comparison 1 (medical/surgical masks). There was no mention of adverse events related to hand hygiene.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness, e.g. pneumonia

Not reported.

Comparison 5: Hand hygiene + medical/surgical masks compared to hand hygiene

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI and laboratory‐confirmed influenza)

Three trials studied the addition of medical/surgical masks to hand hygiene (Cowling 2009; Larson 2010; Simmerman 2011). All three trials had three arms, and are also included in the comparison of hand hygiene plus medical/surgical mask versus control (Comparison 4). All three studies showed no difference between hand hygiene plus medical/surgical mask groups and hand hygiene alone, for all outcomes. The estimates of effect suggested little or no difference when adding masks to hand hygiene compared to hand hygiene alone: for the outcome ILI (RR 1.03, 95% CI 0.69 to 1.53; 3 trials) and the outcome laboratory‐confirmed influenza (RR 0.99, 95% CI 0.69 to 1.44), the estimates of effect were not different and the CIs were relatively wide, suggesting little or no difference (Analysis 5.1). However, the CIs around the estimates were wide and do not rule out an important benefit.

2. Adverse events related to the intervention

Not reported.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 6: Medical/surgical masks compared to other (non‐N95) masks

One trial compared medical/surgical masks with cloth masks in hospital healthcare workers (MacIntyre 2015), and another trial compared catechin‐treated masks versus control masks in healthcare workers and staff of hospitals, rehabilitation centres, and nursing homes in Japan (Ide 2016).

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza)

MacIntyre 2015 found that the rate of ILI was higher in the cloth mask arm compared to the medical/surgical masks arm (RR 13.25, 95% CI 1.74 to 100.97).

Ide 2016 did not find a benefit from the catechin‐treated masks over untreated masks on influenza infection rates (adjusted odds ratio (OR) 2.35, 95% CI 0.40 to 13.72; P = 0.34).

2. Adverse events related to the intervention

In MacIntyre 2015 adverse events associated with face mask use were reported in 40.4% (227/562) of HCWs in the medical/surgical mask arm and 42.6% (242/568) in the cloth mask arm (P = 0.45). The most frequently reported adverse events were general discomfort (35.1%; 397/1130) and breathing problems (18.3%; 207/1130). Laboratory tests showed the penetration of particles through the cloth masks to be very high (97%) compared with medical/surgical masks (44%). Ide 2016 reported that there were no serious adverse events associated with the intervention.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 7: Soap + water compared to sanitiser, and comparisons of different types of sanitiser

Two trials compared soap and water with sanitiser (Azor‐Martinez 2018; Savolainen‐Kopra 2012). Another trial compared different types of hand sanitiser in a virus challenge study (Turner 2004a; Turner 2004b), and one trial studied the frequency of use of hand sanitiser (Pandejpong 2012). The full results of these four trials are shown in Table 7.

4 Results from trials of soap + water compared to hand sanitisers
StudyComparison (see Table 4 for details of interventions)Reported outcomesResults
Azor‐Martinez 2018cluster‐RCTSpainEducation and hand hygiene with soap and water (HH soap) vs hand hygiene with sanitiser (HH sanitiser) vs usual hand‐washing procedures1. URI incidence rate ratio (primary)
2. Percentage difference in absenteeism days1: HH soap vs control 0.94 (95% CI 0.82 to 1.08); HH sanitiser vs control 0.77 (95% CI 0.68 to 0.88); HH soap vs HH sanitiser 1.21 (95% CI 1.06 to 1.39)
2: HH soap 3.9% vs control 4.2% (P < 0.001); HH sanitiser 3.25% vs control 4.2% (P = 0.026); HH soap 3.9% vs HH sanitiser 3.25% (P < 0.001)
Pandejpong 2012cluster‐RCTThailandAlcohol hand gel applied every 60 minutes vs every 120 minutes vs once before lunch (3 groups).Absent days due to confirmed ILI/present days0.017 in every hour group; 0.025 in every 2 hours group; 0.026 in before lunch group. Statistically significant difference between every hour group and before lunch group, and between every hour and every 2 hours groups
Savolainen‐Kopra 2012cluster‐RCTFinlandHand hygiene with soap and water (IR1 group) vs with alcohol‐based hand rub (IR2 group) vs control (none); intervention groups also received education1. Number of respiratory infection episodes/week
2. Number of reported infection episodes/week
3. Number of reported sick leave episodes/week1. 0.076 in IR1; 0.085 in IR2; 0.080 in control, NS
2: 0.097 in IR1; 0.107 in IR2; 0.104 in control, NS
3: 0.042 in IR1; 0.035 in IR2; 0.035 in control. Significantly higher in IR1 compared with control
Turner 2004a and Turner 2004bRCTCanadaStudy 1. Ethanol vs salicylic acid 3.5% vs salicylic acid 1% and pyroglutamic acid 3.5%
Study 2. Skin cleanser wipe vs ethanol (control)% of volunteers infected with rhinovirus7% in each intervention group; 32% in control (study 1)
22% in intervention, 30% in control (study 2)

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza)

In the trial by Azor‐Martinez 2018, ARI incidence was significantly higher in the soap‐and‐water group compared with the hand sanitiser group (rate ratio 1.21, 95% CI 1.06 to 1.39). In contrast, there was no significant difference between interventions in Savolainen‐Kopra 2012. In the rhinovirus challenge study (Turner 2004a; Turner 2004b), all hand sanitisers tested led to a significant lowering of infection rates, but no differences between sanitisers were observed. The study sample size was small.

2. Adverse events related to the intervention

Two trials stated that no adverse events were observed (Pandejpong 2012; Savolainen‐Kopra 2012).

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

The authors of Azor‐Martinez 2018 also observed a significant benefit for hand sanitiser in reduction in days absent, whereas there was no difference between intervention groups in the Savolainen‐Kopra 2012 trial. The study on frequency of use of sanitiser found that use of sanitiser every hour significantly reduced days absent compared with use every two hours or with use only before the lunch break (Pandejpong 2012).

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 8: Surface/object disinfection (with or without hand hygiene) compared to control

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza)

Six trials contributed data to this comparison (Ban 2015; Carabin 1999; Ibfelt 2015; Kotch 1994; McConeghy 2017; Sandora 2008). Full results of these trials are shown in Table 8. Five of the six trials combined disinfection with other interventions such as hand hygiene education, provision of hand hygiene products, and audits. Ban 2015 utilised a combination of provision of hand hygiene products, and cleaning and disinfection of surfaces, and demonstrated a significant reduction in ARI in the intervention group (OR 0.47, 95% CI 0.48 to 0.65). A similar result was seen in Carabin 1999, with a significant reduction in episodes of ARI. Two studies tested multi component interventions and observed no significant difference in ARI outcomes (Kotch 1994; McConeghy 2017).

5 Results from trials of surface/object disinfection (with or without hand hygiene) compared to control
StudyComparison (see Table 4 for details of interventions)Reported outcomesResults
Ban 2015cluster‐RCTChinaHand hygiene products, surface cleaning and disinfection provided to families and kindergartens vs none1. Respiratory illness
2. Cough and expectoration1. OR 0.47 for intervention to control (95% CI 0.38 to 0.59)
2. OR 0.56 (95% CI 0.48 to 0.65)
Carabin 1999cluster‐RCTCanadaOne‐off hygiene education and disinfection of toys with bleach vs noneDifference in incidence rate for URTI (cluster‐level result)0.28 episodes per 100 child‐days lower in intervention group (95% CI 1.65 lower to 1.08 higher); URTI incidence rate IRR 0.80 (95% CI 0.68 to 0.93)
Ibfelt 2015cluster‐RCTDenmarkDisinfectant washing of linen and toys by commercial company every 2 weeks vs usual carePresence of respiratory viruses on surfacesStatistically significant reduction in intervention group in adenovirus, rhinovirus, RSV, metapneumovirus, but not other viruses including coronavirus
Kotch 1994RCTUSATraining in hand‐washing and diapering and disinfection of surfaces vs noneRespiratory illness incidence rate in:
1. children < 24 months;2. children >= 24 months.1. 14.78 episodes per child‐year in intervention; 15.66 in control2. 12.87 in intervention; 11.77 in control
McConeghy 2017RCTUSAStaff education, cleaning products, and audit of compliance and feedback vs noneInfection ratesUpper respiratory infections not reliably recorded or reported.
Sandora 2008cluster‐RCTUSAHand sanitiser and disinfection of classroom surfaces vs materials about good nutrition (control)Absence due to respiratory illness (multivariable analysis)Rate ratio 1.10 for intervention to control (95% CI 0.97 to 1.24)

One trial compared disinfection alone to usual care (Ibfelt 2015). This study demonstrated a significant reduction in some viruses detected on surfaces in the childcare centres (adenovirus, rhinovirus, respiratory syncytial virus (RSV), and metapneumovirus), but not in other viruses, including coronavirus.

2. Adverse events related to the intervention

Not reported.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Only one study measured this outcome (Sandora 2008), observing no significant difference between groups for the outcome of absence due to respiratory illness (rate ratio for intervention to control 1.10, 95% CI 0.97 to 1.24).

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 9: Complex interventions compared to control

Complex interventions are either multifaceted environmental programmes (such as those in low‐income countries) or combined interventions including hygiene measures and gloves, gowns, and masks.

Four trials studied complex hygiene and sanitation interventions in low‐income country settings (Chard 2019; Hartinger 2016; Huda 2012; Najnin 2019). Full results from these studies are given in Table 9.

6 Results from trials of complex interventions compared to control
StudyComparison (see Table 4 for details of interventions)Reported outcomesResults
Complex hygiene and sanitation interventions compared to control
Chard 2019cluster‐RCTLaosComplex sanitation intervention and education vs nonePupil‐reported symptoms of respiratory infection over 1 weekNS difference between groups. 29% of intervention group; 32% control group; adjusted risk ratio 1.08 (95% CI 0.95 to 1.23)
Hartinger 2016cluster‐RCTPeruCooking and sanitation provision and education vs noneNumber of ARI episodes per child‐yearNS difference between groups. Risk ratio for intervention to control 0.95 (95% CI 0.82 to 1.10)
Huda 2012cluster‐RCTBangladeshSanitation provision and education vs noneRespiratory illness12.6% in intervention group; 13.0% in control group. Not adjusted for multiple outcome measurements. No CIs reported.
Najnin 2019cluster‐RCTBangladeshSanitation and behaviour change intervention (plus cholera vaccine) vs noneRespiratory illness in past 2 days2.8% in intervention group; 2.9% in control group

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza)

All four trials of complex interventions observed no significant differences between groups in rates of viral respiratory illness.

2. Adverse events related to the intervention

Not reported.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 10: Physical distancing/quarantine

We found three RCTs that assessed physical distancing/quarantine interventions. A quasi‐cluster‐RCT assessed the effectiveness of quarantining workers of one of two sibling companies in Japan whose family members developed an ILI during the 2009 to 2010 H1N1 influenza pandemic (Miyaki 2011). Workers in the intervention group were asked to stay home on full pay until five days after the household member(s) showed resolution of symptoms or two days after alleviation of fever. A second RCT conducted during the SARS‐CoV‐2 pandemic investigated whether attending fitness centres with physical distancing  was non‐inferior compared to no access in terms of COVID‐19 transmission (Helsingen 2021). The third study was a cluster‐RCT conducted during the SARS‐CoV‐2 pandemic that compared voluntary daily lateral flow device testing for seven days with negative contacts remaining at school to self‐isolation of school‐based COVID‐19 contacts for 10 days in a non‐inferiority design (Young 2021).

Primary outcomes

1. Numbers of cases of viral respiratory illness (including laboratory‐confirmed influenza and SARS‐CoV‐2)

Miyaki 2011 reported adherence with the intervention was 100%. In the intervention group 2.75% of workers contracted influenza, compared with 3.18% in the control group (Cox hazard ratio 0.799, 95% CI 0.66 to 0.97; P = 0.02), indicating that the rate of infection was reduced by 20% in the intervention group. However, the risk of a worker being infected was 2.17‐fold higher in the intervention group where workers stayed at home with their infected family members. The authors concluded that quarantining workers who have infected household members could be a useful additional measure to control the spread of respiratory viruses in an epidemic setting.

Helsingen 2021 reported 3016 participants were tested for SARS‐CoV‐2 resulting in one positive case in the fitness centre access arm versus zero in the no access arm at 14 days (risk difference (RD) 0.053%, 95% CI − 0.050 to 0.156%;  P = 0.32). In addition, 11 in the fitness centre access arm versus 27 in the no access arm tested positive for SARS‐CoV‐2 antibodies at one month (RD − 0.87%, 95% CI − 1.52% to − 0.23%; P = 0.001). The authors concluded that access to fitness centres with physical distancing and low population prevalence of SARS‐CoV‐2 infection did not increase risk of SARS‐CoV‐2 infection.

Results from Young 2021 suggested no difference between the two treatment arms for SARS‐CoV‐2 infection (RR 0.96, 95% CI 0.75 to 1.22) leading the study authors to conclude non‐inferiority of daily contact testing of school‐based contacts (intervention) compared to self‐isolation (control).

2. Adverse events related to the intervention

Not reported.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Young 2021 reported COVID‐19 related absences from school were similar in the two treatment groups (RR 0.80, 95% CI  0.54 to 1.19).

4. Hospital admissions

Helsingen 2021 reported no hospital admissions in either treatment arm.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 11: Eye protection compared to control

Primary outcomes

1. Numbers of cases of viral respiratory illness (including laboratory‐confirmed influenza and SARS‐CoV‐2)

We only identified one trial of eye protection which was a preprint only (Fretheim 2022a). This was a pragmatic RCT conducted in Norway from 2 February to 24 April 2022, where 3717 participants were randomised to an intervention group asked to wear glasses (e.g. sunglasses) for two weeks when close to others in public spaces. COVID‐19 cases in the national registry were 3.7% in the intervention group (68/1852) and 3.5% (65/1865) in the control group (RR 1.10, 95% CI 0.75 to 1.50). Positive COVID‐19 tests based on self‐reporting were 9.6% and 11.5% (RR 0.83, 95% CI 0.69 to 1.00). Given the high risk of bias and wide CIs, no policy conclusions can be drawn, but replication studies are clearly warranted. Almost a third of the participants reported respiratory infections. However, a lower proportion of those (215 participants) were in the intervention group compared to the control group (RR 0.90; 95% CI 0.82 to 0.99).

2. Adverse events related to the intervention

A total of 76 participants reported a negative experience from participating in the trial (53 in the intervention group and 23 in the control group). The most common complaint related to the combination of wearing glasses and face masks, and 21 participants in the intervention group cited fogging as an issue. Some participants reported feeling tired or uncomfortable wearing glasses, and a few participants complained of reduced vision when wearing sunglasses or reading glasses. In the control group some participants reported headaches from not being able to wear glasses, and one participant in the intervention group reported a fall due to reduced vision.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness, e.g. pneumonia

Not reported.

Comparison 12: Gargling/nose rinsing compared to control

Five trials investigated the effect of gargling/nose rinsing. Satomura 2005 compared throat gargling with povidone‐iodine versus tap water in healthy adults. Ide 2014 compared gargling with green tea versus tap water in high school students, and Goodall 2014 compared gargling with tap water with no gargling in university students. Two additional trials were conducted during the SARS‐CoV‐2 pandemic: Almanza‐Reyes 2021 compared silver mouth wash/nose rinse versus conventional mouthwashes and nose rinse in health workers; and Gutiérrez‐García 2022 compared neutral electrolysed water mouth and nose rinses versus no rinses in health workers.

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza and SARS‐CoV‐2)

Satomura 2005 reported that gargling with tap water reduced the incidence of URTIs compared to the control group (usual care) (hazard ratio (HR) 0.60, 95% CI 0.39 to 0.95). Gargling with povidone‐iodine did not reduce the incidence of URTIs compared to the control group (HR 0.88, 95% CI 0.58 to 1.34).

Goodall 2014 found no difference in laboratory‐confirmed URTIs between the gargling (tap water) and no‐gargling groups (RR for gargling versus no gargling 0.82, 95% CI 0.53 to 1.26; P = 0.36).

In a meta‐analysis of gargling versus control based on two trials the pooled estimate of effect suggested little or no difference for the outcome of clinical URTI due to gargling (RR 0.91, 95% CI 0.63 to 1.31; 830 participants; Analysis 6.1) (Goodall 2014; Satomura 2005).

There was no difference in the incidence of laboratory‐confirmed influenza between high school students gargling with green tea compared with those using tap water (adjusted OR 0.69, 95% CI 0.37 to 1.28; P = 0.24) (Ide 2014). There was also no difference in the incidence of clinically defined influenza (adjusted OR 0.75, 95% CI 0.50 to 1.13; P = 0.17). However, the authors reported that adherence to the interventions amongst students was low.

Almanza‐Reyes 2021 reported the incidence of SARS‐CoV‐2 infection was statistically significantly lower in the silver mouth wash/nose rinse group (two out of 114, 1.8%) compared to the conventional mouthwash group (33 out of 117, 28.2%), and Gutiérrez‐García 2022 reported the incidence of COVID‐19‐positive cases in the nasal and oral rinses group was 1% compared to 13% in the control group (RR 0.09, 95% CI of 0.01 to 0.72). A meta‐analysis of these two studies showed a 93% reduction in risk of SARS‐CoV‐2 (RR 0.07, 95% CI 0.02 to 0.23; 394 participants; Analysis 6.2).

2. Adverse events related to the intervention

Satomura 2005 reported no adverse events during the 60‐day intervention period. Ide 2014 also did not observe any adverse events during the study. Goodall 2014 did not report on adverse effects. There were no adverse reactions in the study by Almanza‐Reyes 2021 or side effects in the study by Gutiérrez‐García 2022.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Satomura 2005 reported that the mean peak score in bronchial symptoms was lower in the water gargling group (0.97) than in the povidone‐iodine gargling group (1.41) and the control group (1.40), P = 0.055. Other symptoms were not significantly different between groups. Goodall 2014 reported that symptom severity was greater in the gargling group for clinical and laboratory‐confirmed URTI, but this was not statistically significant (225.3 versus 191.8, and 210.5 versus 191.8, respectively). Ide 2014 did not report symptom or illness severity.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Comparison 13: Virucidal tissues compared to control

Two reports (three trials) conducted in the USA studied the effect of virucidal tissues (Farr 1988a; Farr 1988b; Longini 1988). Full results from these studies are given in Table 10.

7 Results from trials of virucidal tissues compared to control
StudyComparisonReported outcomesResults
Virucidal tissues compared with placebo or no tissues
Farr 1988a and Farr 1988bcluster‐RCTUSA Trial 1 and Trial 2Trial 1. Virucidal nasal tissues vs placebo vs noneTrial 2. Virucidal nasal tissues vs placeboRespiratory illnesses per person over 24 weeks
Trial 1
Trial 2Trial 1: 3.4 in tissues group; 3.9 in placebo group; 3.6 in no‐tissues group
Trial 2: 3.4 in tissues group; 3.6 in placebo group
NS
Longini 1988DB‐PC RCTUSAVirucidal nasal tissues vs placeboSecondary attack rate of viral infections (number of infections in household members of index case)10.0 in intervention; 14.3 in placebo; NS

Primary outcomes

1. Numbers of cases of viral respiratory illness (including ARIs, ILI, and laboratory‐confirmed influenza)

The three trials of virucidal tissues reported no differences in infection rates between tissues and placebo, and between tissues and no tissues (Farr 1988a; Farr 1988b; Longini 1988).

2. Adverse events related to the intervention

Farr 1988b reported cough in 4% of participants using virucidal tissues versus 57% in the placebo group, but 24% reported nasal burning in the virucidal tissue group versus 8% in the placebo group. Longini 1988 did not report on adverse effects.

Secondary outcomes

1. Deaths

Not reported.

2. Severity of viral respiratory illness as reported in the studies

Not reported.

3. Absenteeism

Not reported.

4. Hospital admissions

Not reported.

5. Complications related to the illness (e.g. pneumonia)

Not reported.

Discussion

Summary of main results

See Table 11.

8 Summary of main results of the review for the primary outcomes
Interventions RCT/cluster‐RCT (N = 78)
Medical/surgical masksMasks (medical/surgical) compared to no masks
9 trials in the community showed no effect on ILI (RR 0.95, 0.84 to 1.09) (Abaluck 2022; Aiello 2010; Alfelali 2020; Barasheed 2014; Canini 2010; Cowling 2008;; MacIntyre 2009;; MacIntyre 2016; Suess 2012); and 6 trials in the community showed no effect on laboratory‐confirmed influenza 95% CI RR 1.01 (0.72 to 1.42) (Aiello 2012; Alfelali 2020; Bundgaard 2021; Cowling 2008; MacIntyre 2009; Suess 2012). Two trials in health care workers where the control group wore masks if they were required provided inconclusive results with very wide confidence intervals (Jacobs 2009; MacIntyre 2015).Medical/surgical masks versus other (non‐N95) masks: 1 trial showed more ILI with cloth mask (RR 13.25, 1.74 to 100.97) (MacIntyre 2015); 1 trial showed no effect of catechin‐treated masks on influenza (adjusted OR 2.35, 0.40 to 13.72) (Ide 2016).
N95 respiratorN95 respirators compared to medical/surgical masks3 trials showed no difference for clinical respiratory illness (RR 0.70, 0.45 to 1.10) (MacIntyre 2011; MacIntyre 2013; Radonovich 2019);4 trials showed no difference for ILI (95% CI RR 0.81, 0.62 to 1.05) (Loeb 2009; MacIntyre 2009; MacIntyre 2011; Radonovich 2019); and 4 trials showed no difference for laboratory‐confirmed influenza (95% CI RR 1.06, 0.81 to 1.38) (Loeb 2009; MacIntyre 2009; MacIntyre 2011; Radonovich 2019). 4 trials conducted in HCWs: 3 trials showed no difference for clinical respiratory illness (RR 0.70, 0.45 to 1.10) (MacIntyre 2011; MacIntyre 2013; Radonovich 2019); 3 trials  showed no difference for ILI (RR 0.64, 0.32 to 1.31) (Loeb 2009; MacIntyre 2011; Radonovich 2019); and 3 trials showed no difference for laboratory‐confirmed ILI (RR 1.02, 0.73 to 1.43) (Loeb 2009; MacIntyre 2011; Radonovich 2019).
Hand hygieneHand hygiene compared to control
19 trials found an effect on combined outcome (ARI or ILI or influenza) (RR 0.89, 0.83 to 0.94) (Ashraf 2020; Azor‐Martinez 2018; Biswas 2019; Correa 2012; Cowling 2008; Cowling 2009; Hubner 2010; Larson 2010; Little 2015; Millar 2016; Nicholson 2014; Ram 2015; Roberts 2000; Sandora 2005; Simmerman 2011; Stebbins 2011; Swarthout 2020; Teesing 2021; Zomer 2015); 9 trials showed an effect on ARI (RR 0.86, 0.81 to 0.90) (Ashraf 2020; Azor‐Martinez 2018; Correa 2012; Larson 2010; Little 2015; Millar 2016; Nicholson 2014; Sandora 2005; Swarthout 2020); 11 trials showed no effect on ILI (RR 0.94, 0.81 to 1.09) (Biswas 2019; Cowling 2008; Cowling 2009; Hubner 2010; Larson 2010; Little 2015; Ram 2015; Roberts 2000; Simmerman 2011; Teesing 2021; Zomer 2015); and 8 trials no effect on laboratory‐confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30) (Biswas 2019; Cowling 2008; Cowling 2009; Hubner 2010; Larson 2010; Ram 2015; Simmerman 2011; Stebbins 2011).
Hand hygiene + medical/surgical masksHand hygiene + medical/surgical masks compared to control7 trials showed no effect on ILI (95% CI RR 0.97, 0.80 to 1.19) (Aelami 2015; Aiello 2010; Aiello 2012; Cowling 2009; Larson 2010; Simmerman 2011; Suess 2012); and 4 trials showed no effect on laboratory‐confirmed influenza (RR 0.97, 0.69 to 1.36) (Cowling 2009; Larson 2010; Simmerman 2011; Suess 2012).Hand hygiene + medical/surgical masks compared to hand hygiene
3 trials showed no effect on ILI (RR 1.03, 0.69 to 1.53) or laboratory‐confirmed influenza (RR 0.99, 0.69 to 1.44) (Cowling 2009; Larson 2010; Simmerman 2011).
Soap + water compared to sanitiser, and comparisons of different types of sanitiserSoap + water compared to sanitiser, and comparisons of different types of sanitiser1 trial hand sanitiser was more effective than soap and water (Azor‐Martinez 2018); 1 trial there was no difference (Savolainen‐Kopra 2012).2 trials in children antiseptic was more effective (Morton 2004; White 2001); 1 trial in children antiseptic = soap (Luby 2005).1 trial hand sanitisers were better than placebo, but no difference between sanitisers (Turner 2004a); 1 trial no difference between different wipes (Turner 2004b).
Surface/object disinfection (with or without hand hygiene) compared to controlSurface/object disinfection compared to control
2 trials were effective on ARI (Ban 2015; Carabin 1999); 1 trial was effective for viruses detected on surfaces (Ibfelt 2015); 2 trials showed no difference in ARIs (Kotch 1994; McConeghy 2017).
Disinfection of living quarters‐
Complex interventionsComplex interventions compared to control4 trials in low‐income countries found no effect on respiratory viral illness (Chard 2019; Hartinger 2016; Huda 2012; Najnin 2019).
Physical interventions (masks, gloves, gowns combined)‐
Gloves‐
Gowns‐
Physical distancingPhysical distancing compared to self‐isolation1 trial reported 1 positive SARS‐CoV‐2 case in the fitness centre access arm versus 0 in the no access arm (risk difference 0.05%, 95% CI − 0.05 to 0.16%) (Helsingen 2021)
Quarantine in the communityQuarantine compared to control1 trial effective for influenza (Cox hazard ratio 0.799, 95% CI 0.66 to 0.97) (Miyaki 2011).  Daily contact testing compared to self‐isolation1 trial showed non‐inferiority of daily contact testing of school‐based contacts compared to self‐isolation for SARS‐CoV‐2 (RR 0.96, 95% CI 0.75 to 1.22) (Young 2021)
Eye protectionGlasses compared to no glasses
1 pragmatic RCT conducted in Norway wearing any type of eyeglasses when close to other people outside their home (on public transport, in shopping malls etc.), over a 14‐day period. Positive COVID‐19 tests based on self‐reporting were 9.6% and 11.5% (RR 0.83, 95% CI 0.69 to 1.00) (Fretheim 2022a).
GarglingGargling compared to control
1 trial gargling with tap water was effective, povidone‐iodine was not effective (Satomura 2005); 1 trial gargling with green tea was not more effective than tap water (Ide 2014); 1 trial gargling with water was not effective (Goodall 2014); pooling of 2 trials showed no effect of gargling (RR 0.91, 95% CI 0.63 to 1.31) (Goodall 2014; Satomura 2005).Mouth/nose rinse compared to control 2 trials found a large protective effect on SARS‐CoV‐2 (RR 0.07, 0.01 to 0.23) (Almanza‐Reyes 2021; Gutiérrez‐García 2022).
Virucidal tissuesVirucidal tissues compared to control1 trial had a small effect (Farr 1988a) ("The study authors conclude that virucidal tissues have only a small impact upon the overall rate of natural acute respiratory illnesses"); 2 trials showed a non‐significant difference (Farr 1988b; Longini 1988).
Nose wash‐

1. Medical/surgical masks compared to no masks

The pooled estimates of effect from randomised controlled trials (RCTs) and cluster‐RCTs for wearing medical/surgical masks compared to no masks in the community suggests probably little or no difference in interrupting the spread of influenza‐like illness (ILI)/COVID‐19 like illness (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.84 to 1.09; moderate‐certainty evidence), or laboratory‐confirmed influenza/SARS‐CoV‐2 (RR 1.01, 95% CI 0.72 to 1.42; moderate‐certainty evidence). Six trials were cluster‐RCTs, with all participants in the intervention clusters required to wear masks, thus assessing both source control and personal protection. In two trials the clusters were households with a member with new influenza; neither trial found any protective effect (RR 1.03 in 105 households (Canini 2010); RR 1.21 in 145 households (MacIntyre 2009). In two trials the clusters were college dormitories during the influenza season; neither trial found any reduction (RR 1.10 in 37 dormitories (Aiello 2012); RR 0.90 in three dormitories (Aiello 2010)). Two studies were conducted during the COVID‐19 pandemic and their addition had minimal impact on the pooled estimate of effect previously reported from the earlier studies focused on influenza (Abaluck 2022; Bundgaard 2021). We excluded Aiello 2010 from meta‐analysis since we did not consider 'randomisation' of three clusters to three arms was a proper randomised trial.

Less than half of the trials comparing masks with no masks addressed harms of mask wearing (Canini 2010; Cowling 2008; MacIntyre 2015; Suess 2012). Warmth, respiratory difficulties, humidity, and general discomfort were the most frequently reported adverse events. Neither of the RCTs conducted during the COVID‐19 pandemic directly assessed harms of mask wearing. More adults reported no harms compared to children.

In one trial cloth masks were associated with a significantly higher risk of both ILI and laboratory‐confirmed respiratory virus infection in healthcare workers (HCWs) (MacIntyre 2015). In addition, filtration capacity of the two‐ply cotton cloth masks was found to be only 3% and markedly less than with medical/surgical masks based on standardised particle testing. The authors suggested moisture retention, poor filtration, and penetration of the virus through the mask as plausible explanations for the increased risk of infection.

We did not find any randomised trials assessing the effectiveness of barrier interventions using a combination of masks, gloves, and gowns.

2. N95 respirators compared to medical/surgical masks

Comparisons between N95 respirators and medical/surgical masks, used as needed for exposure to at‐risk patients, for the outcomes of clinical respiratory illness and the outcome of laboratory‐confirmed influenza showed estimates of effect suggesting considerable uncertainty for any benefit of N95 respirators for the former outcome and probably little or no difference for the latter outcome. Five trials (four in healthcare settings and one in a household setting) compared N95/P2 respirators with medical/surgical masks. Pooling of three of these trials showed an estimate of effect suggesting considerable uncertainty as to whether there was any benefit comparing N95 respirators and medical/surgical face masks for the outcome of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; very low‐certainty evidence), and that N95 respirators may make little or no difference for the outcome of ILI (RR 0.82, 95% CI 0.66 to 1.03; low‐certainty evidence), and probably little or no difference for the outcome of laboratory‐confirmed influenza (RR 1.10, 95% CI 0.90 to 1.34; moderate‐certainty evidence). The presence of imprecision (wide CIs) and heterogeneity, particularly for the more subjective and less precise outcomes of clinical respiratory illness and ILI compared to laboratory‐confirmed influenza infection, makes it difficult to assess whether there may be a benefit of either medical/surgical masks or N95/P2 respirators. Restricting the pooling to HCWs made no difference to the overall findings. The two trials with the largest event rates were quite consistent in their findings of no significant differences between N95 and medical/surgical masks for the outcomes of laboratory‐confirmed influenza and all laboratory‐confirmed viral infections (Loeb 2009; Radonovich 2019). Three of the trials contributing to this analysis were carried out by members of the same group (MacIntyre 2009; MacIntyre 2011; MacIntyre 2013).

In general, harms were poorly reported or not reported at all in trials comparing N95 respirators with surgical masks. General discomfort resulting in reduced wear adherence was the most frequently reported harm.

3. Hand hygiene compared to control

We found that the estimate of effect may offer a benefit for hand hygiene for the composite outcome 'acute respiratory infections (ARI) or ILI or influenza' (RR 0.89, 95% CI 0.83 to 0.94; low‐certainty evidence), and probably offers a benefit for the outcomes ARI alone (RR 0.86, 95% CI 0.81 to 0.90; moderate‐certainty evidence), and absenteeism (RR 0.64, 95% CI 0.58 to 0.71). An observed estimate of effect in favour of hand hygiene for laboratory‐confirmed influenza, but with wider CIs may be a consequence of smaller sample sizes in conjunction with a more rigorous outcome measure.

4. Hand hygiene + medical/surgical masks compared to control

The estimate of effect of combined hand hygiene and medical/surgical mask interventions compared to control in six (mostly small) trials suggested that the intervention may make little or no difference for the outcomes ILI (RR 1.03, 95% CI 0.77 to 1.37), and laboratory‐confirmed influenza (four trials) (RR 0.97, 95% CI 0.69 to 1.36).

5. Hand hygiene + medical/surgical masks compared to hand hygiene

We also found an estimate of effect suggesting that adding medical/surgical masks to hand hygiene compared to hand hygiene alone may make little or no difference for the outcomes ILI (RR 1.03, 95% CI 0.69 to 1.53; 3 trials), and laboratory‐confirmed influenza (RR 0.99, 95% CI 0.69 to 1.44).

6. Medical/surgical masks compared to other (non‐N95) masks

One trial found that medical/surgical masks were more effective than cloth masks at reducing the rate of ILI (RR 13.25, 95% CI 1.74 to 100.97) (MacIntyre 2015), but the extremely wide CIs make this finding difficult to interpret. One trial did not find a benefit from catechin‐treated masks over untreated masks on influenza infection rates (adjusted odds ratio (OR) 2.35, 95% CI 0.40 to 13.72; P = 0.34) (Ide 2016).

Harms of wearing masks were reported in 40.4% of HCWs using medical/surgical masks, and in 42.6% of those wearing cloth masks (P = 0.45) (MacIntyre 2015). The penetration of particles was higher in cloth masks (97%) compared to medical/surgical masks (44%).

7. Soap + water compared to sanitiser, and comparisons of different types of sanitiser

There were too few trials comparing different types of hand hygiene interventions to be certain of any true differences between soap and water, alcohol‐based hand sanitisers, or other types of interventions. Also, it is uncertain whether the incremental effect of adding virucidals or antiseptics to hand‐washing actually decreased the respiratory disease burden outside the confines of the rather atypical studies. The extra benefit may have been, at least in part, accrued by confounding additional routines.

8. Surface/object disinfection (with or without hand hygiene) compared to control

We identified six trials on surface/object disinfection (with or without hand hygiene), and although they were heterogeneous (and therefore could not be pooled), three of them showed a clear benefit compared to controls (Ban 2015; Carabin 1999; Ibfelt 2015).

We found no RCTs of nose disinfection, or disinfection of living quarters, as described in observational studies reported in Jefferson 2011.

9. Complex interventions compared to control

Four trials studied complex hygiene and sanitation interventions, all in low‐income country settings (Chard 2019; Hartinger 2016; Huda 2012; Najnin 2019). These trials could not be pooled due to the heterogeneity of the interventions and settings. All four trials found no significant differences between groups in the rates of viral respiratory illness.

10. Physical distancing/quarantine compared to control

We identified one trial that evaluated the effect of quarantine and found a reduction in influenza transmission to co‐workers when those with infected household members stayed home from work (Miyaki 2011). However, staying home increased their risk of being infected two‐fold. Two studies conducted during the COVID‐19 pandemic on SARS‐cov‐2 transmission showed (1) non‐inferiority of daily contact testing of school‐based contacts (intervention) compared to self‐isolation (control) (Young 2021); and (2) access to fitness centres with physical distancing and low population prevalence of SARS‐CoV‐2 infection did not increase risk of SARS‐cov‐2 infection (Helsingen 2021).

11. Eye protection compared to control

We only identified one trial of eye protection which was a preprint only (Fretheim 2022a).

12. Gargling compared to control

Three trials addressed the use of gargling in preventing respiratory infections (Goodall 2014; Ide 2014; Satomura 2005). Although the trials used a variety of liquids and different outcomes, pooling the results of the two trials that compared gargling with tap water versus control did not show a favourable effect in reducing URTIs (RR 0.91, 95% CI 0.63 to 1.31) (Goodall 2014; Satomura 2005). Two trials of mouthwash/nose rinse were conducted during the SARS‐cov‐2 pandemic in HCWs: Almanza‐Reyes 2021 compared silver mouth wash/nose rinse versus conventional mouthwashes and nose rinse; and Gutiérrez‐García 2022 compared neutral electrolysed water mouth and nose rinses versus no rinses. Both studies reported large protective effects of the intervention on SARS‐CoV‐2 infection with reported outcomes of  SARS‐C0V‐2 infection in 28.2% and 12.7% in the HCWs not using the interventions versus 1.8% and 1.2% in those using the intervention, despite the use of  full personal protective equipment (PPE) and the high outcome rates raise questions about risk of bias, and no data were provided about baseline rates in other settings with full use of PPE.

13. Virucidal tissues compared to control

Two reports (three trials) identified in Jefferson 2011 studied the effect of virucidal tissues compared to placebo or no tissues (Farr 1988a; Farr 1988b; Longini 1988). These trials found no differences in infection rates and could not be pooled.

Overall completeness and applicability of evidence

Several features need consideration before making generalisations based on the included studies.

The settings of the included studies, which were conducted over five decades, were heterogeneous and ranged from suburban schools, Carabin 1999, to emergency departments, intensive care units, and paediatric wards, Loeb 2009, in high‐income countries; slums in low‐income countries (Luby 2005); and an upper Manhattan immigrant Latino neighbourhood (Larson 2010). Few attempts were made to obtain socio‐economic diversity by (for example) involving more schools in the evaluations of the same programme. We identified only a few studies from low‐income countries, where the vast majority of the burden of ARIs lies and where inexpensive interventions are so critical. Additionally, limited availability of over‐the‐counter medications and national universal comprehensive health insurance provided with consequent physician prescription of symptomatic treatment may further limit the generalisability of findings.

The included trials generally reported few events and were conducted mostly during non‐epidemic periods with the exception of the trials carried out during the influenza H1N1 and SARS‐CoV‐2 pandemics. The large study by Radonovich 2019 is an exception as it crossed over two of the highest reporting years for influenza in the USA between 2010 and 2017 (Elflein 2019). None of the trials were conducted during pandemics of SARS‐CoV‐1or in outbreaks of Middle East respiratory syndrome (MERS).

Of the trials assessing the effect of masks, six were carried out in those at greater exposure (i.e. HCWs) (Jacobs 2009; Loeb 2009; MacIntyre 2011; MacIntyre 2013; MacIntyre 2015; Radonovich 2019). None of these studies included HCWs undertaking aerosol‐generating procedures, for which the World Health Organization (WHO) currently recommends the N95 or equivalent mask. Three trials on hand hygiene interventions were carried out in nursing homes, and included HCWs (McConeghy 2017; Temime 2018; Yeung 2011). The scarcity of RCTs on HCWs limits the generalisability of such results.

The variable quality of the methods of some studies is striking. Incomplete or no reporting of randomisation (Turner 2004a), blinding (Farr 1988a; Farr 1988b), numerators and denominators (Carabin 1999; Kotch 1994), interventions, and cluster coefficients in the relevant trials (Carabin 1999), led to a considerable loss of information. Potential biases were often not discussed.

Inappropriate placebos caused design problems. In some studies the placebo probably carried sufficient effect to dilute the intervention effects (Longini 1988). Two valiant attempts with virucidal tissues probably failed because placebo handkerchiefs were impregnated with a dummy compound that stung the users' nostrils (Farr 1988a; Farr 1988b).

Some studies used impractical interventions. Volunteers subjected to the intervention hand cleaner (organic acids) were not allowed to use their hands between cleaning and virus challenge, so the effect of normal use of the hands on the intervention remains unknown (Turner 2004a; Turner 2004b). Two per cent aqueous iodine painted on the hands, although a successful antiviral intervention, causes unacceptable cosmetic staining, which is impractical for all but those at the highest risk of epidemic contagion (Gwaltney 1980).

Adherence with interventions, especially educational programmes, was a problem for many studies despite the importance of many such low‐cost interventions. Adherence with mask wearing varied; it was generally around 60% to 80%, but was reported to be as low as 40% (see Table 4). Overall, the logistics of carrying out trials that involve sustained behaviour change are demanding, particularly in challenging settings such as immigrant neighbourhoods or students' halls of residence.

The identified trials provided sparse and unsystematic data on adverse effects of the intervention, and few of the RCTs measured or reported adherence with the intervention, which is especially important for the use of medical/surgical masks or N95 respirators. No studies investigated how the level of adherence may have influenced the effect size.

We identified one study assessing the effects of eye protection (Fretheim 2022a), and we identified three studies on physical distancing/quarantine (Helsingen 2021; Miyaki 2011; Young 2021). The dearth of evidence and predominant setting of seasonal viral circulation limits generalisability of our findings to other contexts and any future epidemics due to other respiratory viruses such as the COVID‐19 pandemic although there have been increasing numbers of RCTs and cluster‐RCTs in the latter setting which are adding to the evidence base.

The two recent small trials from Mexico assessing local mouth/nose rinses airways prophylactic as interventions treatments report large but uncertain reductions in transmission to healthcare workers which warrant further study and replication by other investigator (Almanza‐Reyes 2021; Gutiérrez‐García 2022).

Certainty of the evidence

We found the available evidence base identified through our search processes to be of variable quality. Reporting of sequence generation and allocation concealment were poor in 30% to 50% of studies across the categories of intervention comparisons. Given the nature of the intervention comparison, blinding of treatment allocation after randomisation was rarely achieved. Although blinding of outcome assessment is highly feasible and desirable, most outcomes were assessed by self‐reports. Outcomes in some studies were poorly defined, with a lack of clarity as to the possible aetiological agents (bacterial versus viral). Some studies used laboratory‐confirmed outcomes, both adding precision and avoiding indirectness by having an accurate outcome measure and lowering the risk of bias (see Table 12 for heterogeneity of trial outcome definitions). We found no evidence of selective reporting of outcomes within the included studies. We believe publication bias is unlikely, as the included studies demonstrated a range of effects, both positive and negative, over all study sizes. The variable quality of the studies hampers drawing any firm conclusions.

9 Trial authors’ outcome definitions
StudyOutcome definitions
Masks (n = 16)
Abaluck 2022cluster‐RCTBangladeshCOVID‐19 symptoms as per the WHO case definition of probable COVID‐19 given epidemiological risk factors: (i) fever and cough; (ii) 3 or more of the following symptoms (fever, cough, general weakness and/or fatigue, headache, myalgia, sore throat, coryza, dyspnoea, anorexia, nausea, and/or vomiting, diarrhoea, and altered mental status); or (iii) loss of taste or smell. The owner of the household’s primary phone completed surveys by phone or in‐person at weeks 5 and 9 after the start of the intervention. They were asked to report symptoms experienced by any household member  consistent with the WHO.
COVID‐19 case definition. Laboratory: seropositivity was defined by having detectable IgG antibodies in blood samples against SARS‐CoV‐2, using the SCoV‐2 Detect™ IgG ELISA kit (InBios, Seattle, Washington). This assay detects IgG antibodies against the spike protein subunit (S1) of SARS‐CoV‐2.Safety: harms were not directly assessed in this study, but it is stated no adverse events were reported. 
Alfelali 2020cluster‐RCTHaj in Makkah, Saudi ArabiaLaboratory: swabs were placed it into UTM™ (COPAN) viral transport media. Swabs labelled with the participant’s unique barcode number were stored in an icebox at –20˚C before being re‐stored by day’s end in a –80˚C freezer at the laboratory of the Hajj Research Center at Umm Al‐Qura University, Makkah. After Hajj, these swabs were shipped in refrigerated or cold containers to the Centre for Infectious Disease and Microbiology Laboratory Services, Westmead Hospital, NSW, Australia. There, nucleic acid was extracted with the Qiagen bioROBOT EZ instrument (Qiagen, Valencia, CA), and amplification was performed using the Roche LC 480 (Roche Diagnostics GmbH, Mannheim, Germany) instrument. Respiratory viruses were detected using a real‐time, multiplex reverse transcription polymerase chain reaction assay targeting human coronaviruses (OC43, 229E and NL63), influenza A and B viruses, respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3, human metapneumovirus, rhinovirus, enterovirus and adenovirus. Middle East respiratory syndrome coronavirus (MERS‐CoV) assay targeting the upstream region of the E gene (upE) was also performed.Safety: harms of using face masks were difficulty in breathing (26.2%); discomfort (22%); and a small minority (3%) reported feeling hot, sweating, a bad smell or blurred vision with eyeglasses.
Bundgaard 2021RCTDenmarkLaboratory: viral RNA was extracted from swab samples in DNA/RNA Shield (Zymo Research) using Quick‐RNA Microprep Kit (Zymo Research) with the below modifications. 200 µl samples were incubated for 1 min with proteinase K (Qiagen) in a final concentration of 0.2 µg/µl prior to treatment with lysis buffer (Quick‐RNA Microprep Kit). Only a single washing step using 400 µl RNA Wash Buffer (Quick‐RNA Microprep Kit) was performed before elution in 15µl RNase free water.Participants tested for SARS‐CoV‐2 IgM and IgG antibodies in whole blood using a point‐of‐care test (Lateral Flow test [Zhuhai Livzon Diagnostics]) according to the manufacturer's recommendations. After puncturing a fingertip with a lancet, they withdrew blood into a capillary tube and placed 1 drop of blood followed by 2 drops of saline in the test chamber in each of the 2 test plates (IgM and IgG).Safety: harms were not mentioned as an outcome in the methods, but psychological adverse effects were mentioned, and 14% reported adverse reactions from other people regarding wearing a face mask.
Cowling 2008cluster‐RCTHong KongLaboratory:
QuickVue Influenza A+B rapid test
Viral culture on MDCK (Madin‐Darby canine kidney cells)
Samples were harvested using NTS, but the text refers to a second procedure from June 2007 onwards with testing for influenza viruses on index participants with a negative QuickVue result but a fever ≥ 38 °C who were also randomised and further followed up. Data on clinical signs and symptoms were collected for all participants, and an additional NTS was collected for later confirmation of influenza infection by viral culture. It is noteworthy that dropout was higher in households of index participants who had a negative result on the rapid influenza test (25/44, 57%) compared to those who had a positive result (45/154, 29%).Effectiveness: secondary attack ratios (SAR): SAR is the proportion of household contacts of an index case who subsequently were ill with influenza (symptomatic contact individuals with at least 1 NTS positive for influenza by viral culture or PCR)3 clinical definitions were used for secondary analysis:fever ≥ 38 °C or at least 2 of the following symptoms: headache, coryza, sore throat, muscle aches and pains;at least 2 of the following S/S: fever ≥ 37.8 °C, cough, headache, sore throat and muscle aches and pains; andfever of ≥ 37.8 °C plus cough or sore throat.Safety: harms were not mentioned as an outcome in the methods, but it was reported in the results that there were no adverse events.
Jacobs 2009RCT
JapanLaboratory‐confirmation not reported.Effectiveness: URTI is defined on the basis of a symptom score with a score > 14 being a URTI according to Jackson’s 1958 criteria ("Jackson score"). These are not explained in text, although the symptoms are listed in Table 3 (any, sore throat, runny nose, stuffy nose, sneeze, cough, headache, earache, feel bad) together with their mean and scores (SD) by intervention arm.Safety: the text does not mention or report harms. These appear to be indistinguishable from URTI symptoms (e.g. headache, which is reported as of significantly longer duration in the intervention arm). Compliance is self‐reported as high (84.3% of participants).
Loeb 2009cluster‐RCT
HCW
CanadaClinical respiratory illness, influenza‐like illness, and laboratory‐confirmed respiratory virus infection.Clinical respiratory illness, defined as 2 or more respiratory symptoms or 1 respiratory symptom and a systemic symptom.Influenza‐like illness, defined as fever ≥ 38 °C plus 1 respiratory symptom.Laboratory‐confirmed viral respiratory infection. Laboratory confirmation was by nucleic acid detection using multiplex RT‐PCR for 17 respiratory viruses.Safety: harms were not mentioned as an outcome in the methods, but it is stated in the results that no adverse events were reported by participants.
MacIntyre 2009
cluster‐RCT
Australia Eligibility criteria were stipulated as follows:the household contained > 2 adults > 16 years of age and 1 child 0 to 15 years of age;the index child had fever (temperature > 37.8 °C) and either a cough or sore throat;the child was the first and only person to become ill in the family in the previous 2 weeks;adult caregivers consented to participate in the study; andthe index child was not admitted to the hospital.Definitions used for outcomes:ILI defined by the presence of fever (temperature > 37.8 °C), feeling feverish or a history of fever, > 2 symptoms (sore throat, cough, sneezing, runny nose, nasal congestion, headache), or 1 of the symptoms listed plus laboratory confirmation of respiratory viral infection.Laboratory confirmation: multiplex RT‐PCR tests to detect influenza A and B and RSV, PIV types 1 to 3, picornaviruses (enteroviruses or rhinoviruses), adenoviruses, coronaviruses 229E and OC43, and hMPV plus > 1 symptomEffectiveness: presence of ILI or a laboratory diagnosis of respiratory virus infection within 1 week of enrolment.Safety: harms not mentioned as an outcome in the methods, but it is reported in the results that more than 50% of participants reported concerns with mask wearing, mainly that wearing a face mask was uncomfortable, but there were no significant differences between the P2 (N95) and surgical mask groups. Other concerns were that the child did not want the parent wearing a mask.
Aiello 2010cluster‐RCTUSALaboratory details are described in appendix.Effectiveness: ILI, defined as cough and at least 1 constitutional symptom (fever/feverishness, chills, headache, myalgia). ILI cases were given contact nurses phone numbers to record the illness and paid USD 25 to provide a throat swab. 368 participants had ILI, 94 of which had a throat swab analysed by PCR. 10 of these were positive for influenza (7 for A and 3 for B), respectively by arm 2, 5 and 3 using PCR, 7 using cell culture.Safety: no outcomes on harms planned or reported.
Canini 2010cluster‐RCT
USAThe primary endpoint was the proportion of household contacts who developed an ILI during the 7 days following inclusion. Exploratory cluster‐level efficacy outcome, the proportion of households with 1 or more secondary illness in household contacts.A temperature over 37.8 °C with cough or sore throat was used as primary clinical case definition.The authors also used a more sensitive case definition based on a temperature over 37.8 °C or at least 2 of the following: sore throat, cough, runny nose, or fatigue.Safety: adverse reactions due to mask wearing were reported, with 38 (75%) participants in the intervention arm experiencing discomfort with mask use due to warmth (45%), respiratory difficulties (33%), and humidity (33%). Children wearing children face masks reported feeling pain more frequently than other participants wearing adult face masks (P  =  0.036).
Aiello 2012cluster‐RCT in halls of residence in the USAClinically verified ILI ‐ case definition (presence of cough and at least 1 or more of fever/feverishness, chills, or body aches)Laboratory‐confirmed influenza A or B. Throat swab specimens were tested for influenza A or B using real‐time PCR.Safety: no outcomes on harms planned or reported.
Barasheed 2014cluster‐RCT
Saudi ArabiaLaboratory: 2 nasal swabs from all ILI cases and contacts. 1 for influenza POCT using the QuickVue Influenza (A+B) assay (Quidel Corporation, San Diego, USA) and 1 for later NAT for influenza and other respiratory viruses. However, there was a problem with getting POCT on time during Hajj.Effectiveness: to assess the effectiveness of face masks in the prevention of transmission of ILI. ILI was defined as subjective (or proven) fever plus 1 respiratory symptom (e.g. dry or productive cough, runny nose, sore throat, shortness of breath).Safety: no outcomes on harms planned or reported.
MacIntyre 2011cluster‐RCT
China  Clinical respiratory illnessInfluenza‐like illnessLaboratory‐confirmed viral respiratory infectionLaboratory‐confirmed influenza A or BClinical respiratory illness, defined as 2 or more respiratory or 1 respiratory symptom and a systemic symptom.Influenza‐like illness, defined as fever ≥ 38 °C plus 1 respiratory symptom (i.e. cough, runny nose, etc.).Laboratory‐confirmed viral respiratory infection (detection of adenoviruses, human metapneumovirus, coronavirus 229E ⁄ NL63, parainfluenza viruses 1, 2, and 3, influenza viruses A and B, respiratory syncytial virus A and B, rhinovirus A/B and coronavirus OC43/HKU1 by multiplex PCR).Laboratory‐confirmed influenza A or B.Adherence with mask/respirator use.Safety: adherence and adverse effects of mask wearing were collected at exit interviews 4 weeks' post study. Significantly higher adverse events with N95 respirator compared to medical mask for discomfort, headache, difficulty breathing, nose pressure, trouble communicating, not wearing, and unspecified “other” side effects. Over 50% of those wearing N95 respirators reported adverse events. Of those wearing medical masks versus N95 respirators, 85.5% (420/491) versus 47.4% (447/943) reported no adverse events (P < 0.001), respectively.
MacIntyre 2013
cluster‐RCT
China Laboratory:Laboratory‐confirmed viral respiratory infection in symptomatic participants, defined as detection of adenoviruses; human metapneumovirus; coronaviruses 229E/NL63 and OC43/HKU1; parainfluenza viruses 1, 2, and 3; influenza viruses A and B; respiratory syncytial viruses A and B; or rhinoviruses A/B by NAT using a commercial multiplex PCR (Seegen, Inc., Seoul, Korea).Laboratory‐confirmed influenza A or B in symptomatic participants.Laboratory‐confirmed bacterial colonisation in symptomatic participants, defined as detection of Streptococcus pneumoniae, Legionella, Bordetella pertussis, Chlamydia, Mycoplasma pneumoniae, or Haemophilus influenzae type B by multiplex PCR (Seegen, Inc.).Effectiveness: clinical respiratory illness defined as 2 or more respiratory symptoms or 1 respiratory symptom and a systemic symptom. ILI defined as fever (38 °C) plus 1 respiratory symptom.Safety: adverse effects measured using a semi‐structured questionnaire. Investigators stated that there was higher reported adverse effects and discomfort of N95 respirators compared with the other 2 arms. In terms of comfort, 52% (297 of 571) of the medical mask arm reported no problems, compared with 62% (317 of 512) of the targeted arm and 38% (217 of 574) of the N95 arm (P < 0.001).
MacIntyre 2015cluster‐RCT
VietnamClinical respiratory illness, influenza‐like illness, and laboratory‐confirmed respiratory virus infection.Clinical respiratory illness, defined as 2 or more respiratory symptoms or 1 respiratory symptom and a systemic symptom.Influenza‐like illness, defined as fever ≥ 38 °C plus 1 respiratory symptom.Laboratory‐confirmed viral respiratory infection. Laboratory confirmation was by nucleic acid detection using multiplex RT‐PCR for 17 respiratory viruses.Safety: adverse events associated with face mask use were reported in 40.4% (227/562) of HCWs in the medical/surgical mask arm and 42.6% (242/568) in the cloth mask arm (P = 0.45). The most frequently reported adverse events were: general discomfort (35.1%; 397/1130) and breathing problems (18.3%; 207/1130). The rate of ILI was higher in the cloth mask arm compared to medical/surgical masks (RR 13.25, 95% CI 1.74 to 100.97).
MacIntyre 2016
cluster‐RCT
ChinaClinical respiratory illness, influenza‐like illness, and laboratory‐confirmed viral respiratory infection.Clinical respiratory illness, defined as 2 or more respiratory symptoms (cough, nasal congestion, runny nose, sore throat, or sneezes) or 1 respiratory symptom and a systemic symptom (chill, lethargy, loss of appetite, abdominal pain, muscle or joint aches).Influenza‐like illness, defined as fever ≥ 38 °C plus 1 respiratory symptom.Laboratory‐confirmed viral respiratory infection, defined as detection of adenoviruses, human metapneumovirus, coronaviruses 229E/NL63 and OC43/HKU1, parainfluenza viruses 1, 2, and 3, influenza viruses A and B, respiratory syncytial virus A and B, or rhinovirus A/B by NAT using a commercial multiplex PCR.Safety: no outcomes on harms planned or reported.
Radonovich 2019cluster‐RCT
USALaboratory. Primary outcome: incidence of laboratory‐confirmed influenza, defined as:detection of influenza A or B virus by RT‐PCR in an upper respiratory specimen collected within 7 days of symptom onset;detection of influenza from a randomly obtained swab from an asymptomatic participant; andinfluenza seroconversion (symptomatic or asymptomatic), defined as at least a 4‐fold rise in haemagglutination inhibition antibody titres to influenza A or B virus between pre‐season and postseason serological samples deemed not attributable to vaccination.Effectiveness. Secondary outcomes: incidence of 4 measures of viral respiratory illness or infection as follows:acute respiratory illness with or without laboratory confirmation;laboratory‐detected respiratory infection, defined as detection of a respiratory pathogen by PCR or serological evidence of infection with a respiratory pathogen during the study surveillance period(s), which was added to the protocol prior to data analysis; andlaboratory‐confirmed respiratory illness, identified as previously described (defined as self‐reported acute respiratory illness plus the presence of at least PCR–confirmed viral pathogen in a specimen collected from the upper respiratory tract within 7 days of the reported symptoms and/or at least a 4‐fold rise from pre‐intervention to postintervention serum antibody titres to influenza A or B virus).Influenza‐like illness, defined as temperature of at least 100 °F (37.8 °C) plus cough and/or a sore throat, with or without laboratory confirmation.Safety: 19 participants reported skin irritation or worsening acne during years 3 and 4 at 1 site in the N95 respirator group.
Hand and hygiene (n = 35)
Alzaher 2018cluster‐RCTSaudi ArabiaEpisode of URI was defined as having 2 of the following symptoms for a day or 1 of the symptoms for 2 or more consecutive days: 1) a runny nose, 2) a stuffy or blocked nose or noisy breathing, 3) sneezing, 4) a cough, 5) a sore throat, and 6) feeling hot, having a fever or a chill.
Arbogast 2016cluster‐RCTUSAICD‐9 used: 46611: acute bronchiolitis due to respiratory syncytial virus, 46619: acute bronchiolitis due to other infectious organisms, 4800: pneumonia due to adenovirus, 4809: viral pneumonia, unspecified, 4870: influenza with pneumonia, 07999: unspecified viral infection, 4658: acute upper respiratory infections of other multiple sites, 4659: acute upper respiratory infections of unspecified site, 4871: influenza with other respiratory manifestations.
Ashraf 2020cluster‐RCTBangladeshMain outcome: 7‐day prevalence of acute respiratory infection (ARI), defined as caregiver‐reported symptoms of persistent cough or panting, wheezing, or difficulty breathing (1 or 2) in the 7 days before the interview.
Azor‐Martinez 2016RCTSpainUpper respiratory illness was defined as 2 of the following symptoms during 1 day, or 1 of the symptoms for 2 consecutive days: (1) runny nose; (2) stuffy or blocked nose or noisy breathing; (3) cough; (4) feeling hot or feverish or having chills; (5) sore throat; or (6) sneezing.
Azor‐Martinez 2018RCTSpainRespiratory illness (RI) was defined as the presence of 2 of the following symptoms during 1 day or the presence of 1 of the symptoms for 2 consecutive days: (1) runny nose, (2) stuffy or blocked nose or noisy breathing, (3) cough, (4) feeling hot or feverish or having chills, (5) sore throat, or (6) sneezing.ICD‐10 and ICD‐9 diagnosis codes used: nonspecific upper respiratory tract infection (465.9), otitis media (382.9), pharyngotonsillitis (463), lower respiratory tract infections (485 and 486), acute bronchitis (490), and bronchiolitis (466.19). Study authors combined the bronchopneumonia code (485) and pneumonia code (486) under the label “lower respiratory tract infections.” If > 1 antibiotic was prescribed during an episode, they used the first prescription for analysis. The final diagnosis was done by the medical researchers on the basis of the symptoms described above and a review of the medical history of children with RIs.
Biswas 2019cluster‐RCTBangladeshInfluenza‐like illness: an ILI episode was defined as measured fever > 38 °C or subjective fever and cough.Laboratory‐confirmed influenzaNasal swabs for real‐time RT‐PCR.
Correa 2012cluster‐RCTColombiaAcute respiratory infection was defined as 2 or more of the following symptoms for at least 24 hours, lasting at least 2 days: runny, stuffy, or blocked nose or noisy breathing; cough; fever, hot sensation, or chills; and/or sore throat. Ear pain alone was considered ARI alternately.
Cowling 2009cluster‐RCTHong Kong Laboratory‐confirmed of influenza virus infection by RT‐PCR for influenza A and B virus.Clinical influenza‐like illness: used 2 clinical definitions of influenza based on self‐reported data from the symptom diaries as secondary analyses. The first definition of clinical influenza was at least 2 of the following signs and symptoms: temperature 37.8 °C or greater, cough, headache, sore throat, and myalgia; the second definition was temperature 37.8 °C or greater plus cough or sore throat.
DiVita 2011 (conference abstract)RCTBangladeshInfluenza‐like illness was defined as fever in children < 5 years old and fever with cough or sore throat in individuals > 5 years old.
Feldman 2016cluster‐RCTIsraelInfectious diseases grouped into diarrhoeal, respiratory, and skin infection. Based on ICD‐9, but no supplementary material was accessible for further definition (Supplementary Material C lists all ICD‐9 diagnoses tallied in this ”outcome”).
Gwaltney 1980
RCTUSAViral cultures and serology if rhinovirus in laboratory‐inoculation
Hubner 2010RCTGermanyAssessing illness rates due to common cold and diarrhoea. Collecting data on illness symptoms (common cold, sinusitis, sore throat, fever, cough, bronchitis, pneumonia, influenza, diarrhoea) and associated absenteeism at the end of every month.Definitions of symptoms were given to the participants as part of the individual information at the beginning of the study. Whilst most symptoms are quite self‐explanatory, "influenza" and "pneumonia" are specific diagnoses that were confirmed by professional diagnosis only. Similarly, (self‐) diagnosis of "fever" required objective measurement with a thermometer.
Ladegaard 1999RCTDenmarkLaboratory: serological evidenceEffectiveness: influenza‐like illness (described as fever, history of fever or feeling feverish in the past week, myalgia, arthralgia, sore throat, cough, sneezing, runny nose, nasal congestion, headache).
However, a positive laboratory finding for influenza converts the ILI definition into one of influenza.
Larson 2010cluster‐RCTUSAStudy goals: rates of symptoms and secondary transmission of URIs, incidence of virologically confirmed influenza, knowledge of prevention and treatment strategies for influenza and URIs, and rates of influenza vaccination.Laboratory‐confirmed influenza: nasal swabs to test for influenza types A and B as well as other common respiratory viruses by rapid culture (R‐Mix, Diagnostic Hybrids, Inc., Athens, OH, USA). PCR and subtyping of the samples was done during the second half of the second year of the study.Influenza‐like illness: CDC definition of ILI from the Sentinel Physicians' Network was used to determine when masks should be worn: “temperature of ≥37.8°C and cough and/or sore throat in the absence of a known cause other than influenza".Episodes of URI = upper respiratory infection: not clear, no explicitly stated definition, reported that the most commonly reported URI symptoms are cough or rhinorrhoea.
Little 2015RCTEnglandRespiratory tract infections defined as 2 symptoms of an RTI for at least 1 day or 1 symptom for 2 consecutive days. For reported ILI, study authors did not use WHO or CDC definitions because these definitions require measured temperature, and thus were not appropriate (participants were not included after a clinical examination), and they did not use the European Centre for Disease Prevention and Control definition (1 systemic and 1 respiratory symptom) because, according to the international influenza collaboration, this definition does not necessarily differentiate ILI from a common cold. Influenzanet suggests making high temperature a separate element. Their pragmatic definition of ILI therefore required a high temperature (feeling very hot or very cold; or measured temperature > 37.5 °C), a respiratory symptom (sore throat, cough, or runny nose), and a systemic symptom (headache, severe fatigue, severe muscle aches, or severe malaise).
Luby 2005RCTPakistanDefined pneumonia in children according to the WHO clinical case definition: cough or difficulty breathing with a raised respiratory rate (> 60 per minute in individuals younger than 60 days old, > 50 per minute for those aged 60 to 364 days, and > 40 per minute for those aged 1 to 5 years)
Millar 2016
cluster‐RCTUSAMedically attended, outpatient cases of acute respiratory infection in the study population. The case definition was any occurrence of the following International Classification of Disease, 9 Revision, Clinical Modification (ICD‐9) symptom or disease‐specific codes: 460 to 466, 480 to 488, and specifically 465.9, 482.9, 486, and 487.1.Acute respiratory infections (460 to 466)460 Acute nasopharyngitis (common cold)461 Acute sinusitis462 Acute pharyngitis463 Acute tonsillitis464 Acute laryngitis and tracheitis465 Acute upper respiratory infections of multiple or unspecified sites466 Acute bronchitis and bronchiolitisPneumonia and influenza (480 to 488)480 Viral pneumonia481 Pneumococcal pneumonia (Streptococcus pneumoniae pneumonia)482 Other bacterial pneumonia483 Pneumonia due to other specified organism484 Pneumonia in infectious diseases classified elsewhere485 Bronchopneumonia, organism unspecified486 Pneumonia, organism unspecified487 Influenza488 Influenza due to identified avian influenza virus465.9 Acute upper respiratory infections of unspecified site482.9 Bacterial pneumonia NOS487.1 Diagnosis of influenza with other respiratory manifestations
Morton 2004cluster‐RCTCross‐over studyUSARespiratory illnesses defined by symptoms of upper respiratory infections such as nasal congestion, cough, or sore throat, in any combination, with or without fever
Nicholson 2014cluster‐RCTIndiaAcute respiratory infectionsOperational definitions for all the illnesses were taken from Black's Medical Dictionary. ARIs defined as "Pneumonia, cough, fever, chest pain and shortness of breath, cold, inflammation of any or all of the airways, that is, nose, sinuses, throat, larynx, trachea and bronchi".
Pandejpong 2012cluster‐RCTThailandInfluenza‐like illness defined if 2 or more symptoms of stuffy nose, cough, fever or chills, sore throat, headache, diarrhoea, presence of hand, foot, or mouth ulcers.
Priest 2014cluster‐RCTNew ZealandRespiratory illness was defined as an episode of illness that included at least 2 of the following caregiver‐reported symptoms for 1 day, or 1 of these symptoms for 2 days (but not fever alone): runny nose, stuffy or blocked nose or noisy breathing, cough, fever, sore throat, or sneezing.
Ram 2015RCTBangladeshInfluenza‐like illnessAge‐specific definitions of ILI. For individuals ≥ 5 years old, ILI was defined as history of fever with cough or sore throat. For children < 5 years old, ILI was defined as fever; study authors used this relatively liberal case definition in order to include influenza cases with atypical presentations in children.Laboratory‐confirmed influenza infectionOropharyngeal swabs from index case patients for laboratory testing for influenza. All swabs were tested by PCR for influenza A and B, with further subtyping of influenza A isolates.
Roberts 2000cluster‐RCTAustraliaThe symptoms of acute upper respiratory illness elicited from parents were: a runny nose, a blocked nose, and cough. Study authors used a definition of colds based on a community intervention trial of virucidal impregnated tissues.A cold was defined as either 2 symptoms for 1 day or 1 of the respiratory symptoms for at least 2 consecutive days, but not including 2 consecutive days of cough alone. Study authors defined a new episode of a cold as the occurrence of respiratory symptoms after a period of 3 symptom‐free days.
Sandora 2005
cluster‐RCTUSA The overall rates of secondary respiratory and GI illness.Respiratory illness was defined as 2 of the following symptoms for 1 day or 1 of the symptoms for 2 consecutive days: (1) runny nose; (2) stuffy or blocked nose or noisy breathing; (3) cough; (4) fever, feels hot, or has chills; (5) sore throat; and (6) sneezing. An illness was considered new or separate when a period of at least 2 symptom‐free days had elapsed since the previous illness. An illness was defined as a secondary case when it began 2 to 7 days after the onset of the same illness type (respiratory or GI) in another household member.
Savolainen‐Kopra 2012cluster‐RCTFinlandNasal and pharyngeal stick samples from participants with respiratory symptoms
Simmerman 2011cluster‐RCTThailandInfluenza‐like illness defined by WHO as fever plus cough or sore throat, based on self‐reported symptoms.Laboratory‐confirmed secondary influenza virus infections amongst household members described as the secondary attack rate. The secondary influenza virus infection was defined as a positive rRT‐PCR result on days 3 or 7 or a four‐fold rise in influenza HI antibody titres with the virus type and subtype matching the index case.
Stebbins 2011
cluster‐RCTUSAThe primary outcome was an absence episode associated with an influenza‐like illness that was subsequently laboratory‐confirmed as influenza A or B. The following CDC definition for ILI was used: fever ≥ 38 °C with sore throat or cough.
Swarthout 2020cluster‐RCTKenyaThe primary outcome in this study is ARI symptoms ‐ defined as having caregiver‐reported cough or difficulty breathing, including panting or wheezing, within 7 days before the interview ‐ in children younger than 3 years. Prespecified secondary outcomes in this study include difficulty
breathing, including panting or wheezing, in the past 7 days (a more specific indicator of respiratory infection than a cough alone); ARI symptoms presenting with fever in the past 7 days (a potentially more severe infection); and enumerator‐observed runny nose (an objective outcome).
Talaat 2011cluster‐RCTEgyptNasal swab for QuickVue test for influenza A and B viruses.Influenza‐like illness (defined as fever > 38 °C and either cough or sore throat).
Teesing 2021cluster‐RCTThe NetherlandsIncidence of gastroenteritis, ILI, assumed pneumonia, UTIs using the McGeer criteria, and infections caused by MRSA.
Temime 2018cluster‐RCTFranceARIs were defined as the combination of at least 1 respiratory symptom and 1 symptom of systemic infection.
Turner 2004bRCTCanadaVirologic assays
Turner 2012RCTUSALaboratory‐confirmed rhinovirus infection by PCR assay.Common cold illness was defined as the presence of any of the symptoms of nasal obstruction, rhinorrhoea, sore throat, or cough on at least 3 consecutive days. Illnesses separated by at least 3 symptom‐free days were considered as separate illnesses.
Yeung 2011cluster‐RCTHong KongPneumonia
Zomer 2015
cluster‐RCTNetherlandsIncidence of gastrointestinal and respiratory infections in children monitored by parents. The common cold was defined as a blocked or runny nose with at least 1 of the following symptoms: coughing, sneezing, fever, sore throat, or earache.
Hand hygiene and masks (n = 6)
Aelami 2015 (conference abstract)RCTSaudi ArabiaInfluenza‐like illness was defined as the presence of at least 2 of the following during their stay: fever, cough, and sore throat.Safety: no outcomes on harms planned or reported.
Aiello 2010cluster‐RCTUSAInfluenza‐like illness case definition (presence of cough and at least 1 constitutional symptom (fever/feverishness, chills, or body aches).Safety: no outcomes on harms planned or reported.
Cowling 2009cluster‐RCTHong Kong2 clinical definitions of influenza. First definition was at least 2 of the following signs and symptoms: temperature 37.8 °C or greater, cough, headache, sore throat, and myalgia. The second was temperature 37.8 °C or greater plus cough or sore throat.Safety: no outcomes on harms planned or reported.
Larson 2010cluster‐RCTUSAStudy goals: rates of symptoms and secondary transmission of URIs, incidence of virologically‐confirmed influenza, knowledge of prevention and treatment strategies for influenza and URIs, and rates of influenza vaccination.Laboratory‐confirmed influenza: nasal swabs to test for influenza types A and B as well as other common respiratory viruses by rapid culture (R‐Mix, Diagnostic Hybrids, Inc., Athens, OH, USA). PCR and subtyping of the samples was done during the second half of the second year of the study.Influenza‐like illness: CDC definition of ILI from the Sentinel Physicians' Network was used to determine when masks should be worn: “temperature of ≥37.8°C and cough and/or sore throat in the absence of a known cause other than influenza".Episodes of URI = upper respiratory infection: not clear, no explicitly stated definition, reported that the most commonly reported URI symptoms are cough or rhinorrhoea.Safety: no outcomes on harms planned or reported.
Simmerman 2011cluster‐RCTThailandLaboratory‐confirmed secondary influenza virus infections amongst household members described as the secondary attack rate. The secondary influenza virus infection was defined as a positive rRT‐PCR result on days 3 or 7 or a four‐fold rise in influenza HI antibody titres with the virus type and subtype matching the index case.Influenza‐like illness defined by WHO as fever plus cough or sore throat, based on self‐reported symptoms.Safety: no outcomes on harms planned or reported.
Suess 2012cluster‐RCTGermanyQuantitative RT‐PCR for samples of nasal wash.Influenza virus infection as a laboratory‐confirmed influenza infection in a household member who developed fever (> 38.0 °C), cough, or sore throat during the observation period. Also secondary outcome measure of the occurrence of ILI as defined by WHO as fever plus cough or sore throat.Safety: the study reported that the majority of participants (107/172, 62%) did not report any problems with mask wearing. This proportion was significantly higher in the group of adults (71/100, 71%) compared to the group of children (36/72, 50%) (P = 0.005). The main problem stated by participants (adults and children) was "heat/humidity" (18/34, 53% of children; 10/29, 35% of adults) (P = 0.1), followed by "pain" and "shortness of breath" when wearing a face mask.
Surface/object disinfection (with or without hand hygiene)(n = 8)
Ban 2015cluster‐RCTChinaAcute respiratory illness classified as the appearance of 2 or more of the following symptoms: fever, cough and expectoration, runny nose and nasal congestion.
Carabin 1999cluster‐RCTCanadaThe presence of nasal discharge (runny nose) accompanied by 1 or several of the following symptoms: fever, sneezing, cough, sore throat, ear pain, malaise, irritability. A URTI was defined as a cold for 2 consecutive days.
Chard 2019cluster‐RCTLaosPupils were considered to have symptoms of respiratory infection if they reported cough, runny nose, stuffy nose, or sore throat.
Ibfelt 2015cluster‐RCTDenmarkLaboratory confirmation of 16 respiratory viruses: influenza A; influenza B; coronavirus NL63229E, OC43 and HKU1; parainfluenza virus 1, 2, 3, and 4; rhinovirus; RSV A/B; adenovirus; enterovirus; parechovirus; and bocavirus using quantitative PCR
Kotch 1994RCTUSARespiratory symptoms include coughing, runny nose, wheezing or rattling in the chest, sore throat, or earache.
McConeghy 2017RCTUSAClassified infections as lower respiratory tract infections (i.e. pneumonia, bronchitis, or chronic obstructive pulmonary disease exacerbation) or other. 
Sandora 2008cluster‐RCTUSARI was defined as an acute illness that included > 1 of the following symptoms: runny nose, stuffy or blocked nose, cough, fever or chills, sore throat, or sneezing.
White 2001DB‐RCTUSARI was defined as: cough, sneezing, sinus trouble, bronchitis, fever alone, pink‐eye, headache, mononucleosis, and acute exacerbation of asthma. 
Other (miscellaneous) interventions (n = 5)
Fretheim 2022apragmatic RCT
NorwayRespiratory infection was defined as having 1 respiratory symptom (stuffed or runny nose, sore throat, cough, sneezing, heavy breathing) and fever, or 1 respiratory symptom and at least 2 more symptoms (body ache, muscular pain, fatigue, reduced appetite, stomach pain, headache, loss of smell. 
Hartinger 2016cluster‐RCTPeru ARI was defined as a child presenting cough or difficulty breathing, or both. ALRI was defined as a child presenting cough or difficulty breathing, with a raised respiratory rate > 50 per minute in children aged 6 to 11 months and > 40 per minute in children aged > 12 months on 2 consecutive measurements. An episode was defined as beginning on the first day of cough or difficulty breathing and ending with the last day of the same combination, followed by at least 7 days without those symptoms.
Huda 2012cluster‐RCTBangladeshStudy authors classified acute respiratory illness as having cough and fever or difficulty breathing and fever within 48 h prior to interview.
Najnin 2019cluster‐RCTBangladeshClassified participants as having respiratory illness if they reported having fever plus either cough or nasal congestion or fever plus breathing difficult.
Satomura 2005RCTJapanUpper respiratory tract infection defined as all of the following conditions:both nasal and pharyngeal symptoms;severity of at least 1 symptom increased by 2 grades or more; andworsening of a symptom of 1 increment or more for > 3 days.Because of the difference in the mode of transmission, study authors excluded influenza‐like diseases featured by moderate or severe fever; anti‐influenza vaccination in the preseason and arthralgia, and treated them separately. The incidence was determined by 1 study physician who was blinded to group assignment.
Virucidal tissues (n = 2)
Farr 1988acluster‐RCTUSA trial 1 and trial 2RI defined as: occurrence of at least 2 respiratory symptoms on the same day or the occurrence of a single respiratory symptom on 2 consecutive days (except for sneezing). The respiratory symptoms were as follows: sneezing, nasal congestion, nasal discharge, sore throat, scratchy throat, hoarseness, coughing, malaise, headache, feverishness, chilliness and myalgia.
Longini 1988DB‐PC RCTUSARespiratory illness defined as 1 or more of the following symptoms occurring during the course of acute episode: coryza, sore throat or hoarseness, earache, cough, pain on respiration, wheezy breathing or phlegm from the chest.

Potential biases in the review process

The non‐drug (and often locally manufactured) nature of most of the interventions in this review, the lack of effective regulation in some settings, and the possible endless number of manufacturers make it difficult to gauge the existence of unpublished data. Non‐drug interventions typically have no or very loose regulation.

In this 2022 update, we again focused on RCTs and cluster‐RCTs, providing a higher level of evidence compared with the previous version of the review, which also meta‐analysed observational studies when appropriate (Jefferson 2011). However, many of the trials were small and hence underpowered, and at high or unclear risk of bias due to poor reporting of methods and lack of blinding. The populations, outcomes, comparators, and interventions tested were heterogeneous.

Due to the urgency of this update in the context of the COVID‐19 pandemic, we did not contact trial authors to request missing data. This means that we have not considered studies that included other non‐respiratory infections, and did not provide stratified data by type of infection.

Agreements and disagreements with other studies or reviews

Several reviews of RCTs have found broadly similar results to this review for face masks. In a meta‐analysis comparing surgical masks with N95 respirators, Smith 2016 pooled three trials and found an estimate of effect suggesting no difference for laboratory‐confirmed respiratory infections (OR 0.89, 95% CI 0.64 to 1.24) or ILI (OR 0.51, 95% CI 0.19 to 1.41) (Loeb 2009; MacIntyre 2011; MacIntyre 2013). A similar meta‐analysis, Offeddu 2017, based on two trials concluded that masks (either N95/P2 respirators or medical/surgical masks) were effective against clinical respiratory infections (RR 0.59, 95% CI 0.46 to 0.77) and ILI (RR 0.34, 95% CI 0.14 to 0.82) (MacIntyre 2011; MacIntyre 2015). Pooling of two studies (MacIntyre 2011; MacIntyre 2013) also found an estimate of effect that favoured N95 respirators to medical/surgical masks for clinical respiratory infections (RR 0.47, 95% CI 0.36 to 0.62), but not for ILI, (RR 0.59, 95% CI 0.27 to 1.28) based on three studies (Loeb 2009: MacIntyre 2011; MacIntyre 2013). The outcome of clinical respiratory infection is considered to be the most subjective and least precise outcome.

A recent meta‐analysis included five trials comparing N95/P2 respirators with medical/surgical masks and found no difference between groups for either influenza (RR 1.09, 95% CI 0.92 to 1.28), or respiratory viral infections (RR 0.89, 95% CI 0.70 to 1.11) (Long 2020). By excluding Loeb 2009 (an open, non‐inferiority RCT that compared medical/surgical masks with N95 respirators in protecting HCWs against influenza), the authors reported a significant protective effect against viral infections (RR 0.61, 95% CI 0.39 to 0.98). The authors do not report a rationale for the exclusion in the sensitivity analysis, and do not report on exclusion of the studies with low weighting, which arguably would be more relevant in a sensitivity analysis. The two trials that make up 96% of the weighting demonstrated no significant differences in the outcome events (Loeb 2009; Radonovich 2019). A recent meta‐analysis of four RCTs adjusting for clustering, which compared N95 respirators with the use of medical/surgical  masks, found pooled estimates of effect that did not demonstrate any difference in any laboratory‐confirmed viral respiratory infection (OR 1.06, 95% CI 0.90 to 1.25), laboratory‐confirmed influenza (OR 0.94, 95% CI 0.73 to 1.20), or clinical respiratory illness (OR 1.49, 95% CI 0.98 to 2.28), with the evidence profile suggesting that there was greater imprecision and inconsistency in the outcome of clinical respiratory illness (Bartoszko 2020). Moreover, in another recent systematic review that assessed the effectiveness of personal protective and environmental measures in non‐healthcare settings (funded by the WHO), 10 RCTs reporting estimates of the effectiveness of face masks in reducing laboratory‐confirmed influenza virus infections in the community were identified (Xiao 2020). The evidence from these RCTs suggested that the use of face masks either by infected persons or by uninfected persons does not have a substantial effect on influenza transmission.

The findings from several systematic reviews and meta‐analyses over the last decade have not demonstrated any difference in the clinical effectiveness of N95 respirators or equivalent compared to the use of surgical masks when used by HCWs in multiple healthcare settings for the prevention of respiratory virus infections, including influenza.

Reviews based on observational studies have usually found a stronger protective effect for face masks, but have important biases. The review by Chu 2020 did not consider RCTs of influenza transmission, but only the observational studies examining impact on SARS, MERS, or SARS‐CoV‐2. For N95 masks versus no mask in HCWs, there was a large protective effective with an OR of 0.04 (95% CI 0.004 to 0.30); for surgical masks versus no masks, there was an OR of 0.33 (0.17 to 0.61) overall, but four of these studies were in healthcare settings. Chu 2020 has been criticised for several reasons: use of an outdated 'Risk of bias' tool; inaccuracy of distance measures; and not adequately addressing multiple sources of bias, including recall and classification bias and in particular confounding. Confounding is very likely, as preventive behaviours such as mask use, social distancing, and hand hygiene are correlated behaviours, and hence any effect estimates are likely to be overly optimistic.

The two RCTs of medical/surgical masks during the SARS‐CoV‐2 pandemic found uncertain evidence of a small or no effect (Abaluck 2022; Bundgaard 2021). The study by Abaluck 2022 found a statistically significant benefit of masks versus no masks for COVID‐like‐illness, however, this study was rated at high risk of bias for five of the six domains due to issues including baseline imbalance, subjective outcome assessment and incomplete follow‐up across the groups. Despite this study contributing 45% of the weight towards the meta‐analysis of influenza/COVID‐like‐illness for masks versus no masks, the updated conclusions from the analysis strengthened around little or no effect of mask use.

Also based on observational studies, Jefferson 2011 found a protective effect of wearing surgical masks with hygienic measures compared to not wearing masks in the SARS 2003 outbreak (OR 0.32, 95% CI 0.26 to 0.39). However, the evidence was based on case‐control studies carried out during the outbreak. There was some additional but very limited supportive evidence from the cohort studies in Jefferson 2011.

Although the use of eye protection and physical distancing measures are widely believed to be effective in reducing transmission of respiratory viruses and mitigating the impact of an influenza pandemic, we found only one trial investigating the role of self‐quarantine in reducing the incidence of H1N1 influenza events in the workplace, and no trials examining the effect of eye protection. The evidence for these measures was derived largely from observational studies and simulation studies, and the overall certainty of supporting evidence is relatively low. The finding of limited evidence evaluating these interventions was also consistent with a recent review funded by the WHO for the preparation of its guidelines on the use of non‐pharmaceutical interventions for pandemic influenza in non‐medical settings (Fong 2020).

There are several previous systematic reviews on hand hygiene and respiratory infections. Five of them reviewed the evidence in a community setting (Moncion 2019; Rabie 2006; Saunders‐Hastings 2017; Warren‐Gash 2013: Wong 2014), and three focused on children (Mbakaya 2017; Willmott 2016; Zivich 2018). The earliest review in 2006 included eight studies, three of which were RCTs (Rabie 2006). The pooled estimate of seven studies was described as “indicative” of the effect of hand hygiene, but the studies were of poor quality. The Warren‐Gash 2013 review included 16 studies (10 of which were RCTs) and reported mixed and inconclusive results. A 2014 review identified 10 RCTs and reported that the combination of hand hygiene with face masks in high‐income countries (five trials) significantly reduced the incidence of laboratory‐confirmed influenza and ILI, whilst hand hygiene alone did not (Wong 2014). This significant reduction in laboratory‐confirmed influenza and ILI for hand hygiene and face masks may have been based on the raw numbers without adjusting for any clustering effects in the included cluster trials, which produced inappropriately narrow CIs, and possibly biased treatment effect estimates. Moreover, trials from the low‐income countries were not included in the review, and this significant effect was not demonstrated when all the trials identified in the review were combined. The Saunders‐Hastings 2017 review of studies evaluating the effectiveness of personal protective measures in interrupting pandemic influenza transmission only identified two RCTs (Azor‐Martinez 2014; Suess 2012), which reported a significant effect of hand hygiene. The Moncion 2019 review identified seven RCTs of hand hygiene compared to control, with mixed results for preventing the transmission of laboratory‐confirmed or possible influenza. Systematic reviews of RCTs of hand hygiene interventions amongst children, Mbakaya 2017 and Willmott 2016, or at a non‐clinical workplace, Zivich 2018, identified heterogeneous trials with quality problems including small numbers of clusters and participants, inadequate randomisation, and self‐reported outcomes. Evidence of impact on respiratory infections was equivocal.

A rapid search for other systematic reviews of RCTs was conducted in September 2022, and none of high quality were found.

Authors' conclusions

Implications for practiceThe evidence summarised in this review on the use of masks is largely based on studies conducted during traditional peak respiratory virus infection seasons up until 2016. Two relevant randomised trials conducted during the COVID‐19 pandemic have been published, but their addition had minimal impact on the overall pooled estimate of effect. The observed lack of effect of mask wearing in interrupting the spread of influenza‐like illness (ILI) or influenza/COVID‐19 in our review has many potential reasons, including: poor study design; insufficiently powered studies arising from low viral circulation in some studies; lower adherence with mask wearing, especially amongst children; quality of the masks used; self‐contamination of the mask by hands; lack of protection from eye exposure from respiratory droplets (allowing a route of entry of respiratory viruses into the nose via the lacrimal duct); saturation of masks with saliva from extended use (promoting virus survival in proteinaceous material); and possible risk compensation behaviour leading to an exaggerated sense of security (Ammann 2022; Brosseau 2020; Byambasuren 2021; Canini 2010; Cassell 2006; Coroiu 2021; MacIntyre 2015; Rengasamy 2010; Zamora 2006).Our findings show that hand hygiene has a modest effect as a physical intervention to interrupt the spread of respiratory viruses, but several questions remain. First, the high heterogeneity between studies may suggest that there are differences in the effect of different interventions. The poor reporting limited our ability to extract the information needed to assess any 'dose response' relationship, and there are few head‐to‐head trials comparing hand hygiene materials (such as alcohol‐based sanitiser or soap and water). Second, the sustainability of hand hygiene is unclear where participants in some studies achieved 5 to 10 hand‐washings per day, but adherence may have diminished with time as motivation decreased, or due to adverse effects from frequent hand‐washing. Third, there is little evidence about the effectiveness of combinations of hand hygiene with other interventions, and how those are best introduced and sustained. Finally, some interventions were intensively implemented within small organisations, and involved education or training as a component, and the ability to scale these up to broader interventions is unclear. Our findings with respect to hand hygiene should be considered generally relevant to all viral respiratory infections, given the diverse populations where transmission of viral respiratory infections occurs. The participants were adults, children and families, and multiple congregation settings including schools, childcare centres, homes, and offices. Most respiratory viruses, including the pandemic SARS‐CoV‐2, are considered to be predominantly spread via respiratory particles of varying size or contact routes, or both (WHO 2020c). Data from studies of SARS‐CoV‐2 contamination of the environment based on the presence of viral ribonucleic acid and infectious virus suggest significant fomite contamination (Lin 2022; Onakpoya 2022b; Ong 2020; Wu 2020). Hand hygiene would be expected to be beneficial in reducing the spread of SARS‐CoV‐2 similar to other beta coronaviruses (SARS‐CoV‐1, Middle East respiratory syndrome (MERS), and human coronaviruses), which are very susceptible to the concentrations of alcohol commonly found in most hand‐sanitiser preparations (Rabenau 2005; WHO 2020c). Support for this effect is the finding that poor hand hygiene, despite the use of full personal protective equipment (PPE), was independently associated with an increased risk of SARS‐CoV‐2 transmission to healthcare workers in a retrospective cohort study in Wuhan, China in both a high‐risk and low‐risk clinical unit for patients infected with COVID‐19 (Ran 2020). The practice of hand hygiene appears to have a consistent effect in all settings, and should be an essential component of other interventions.The highest‐quality cluster‐RCTs indicate that the most effect on preventing respiratory virus spread from hygienic measures occurs in younger children. This may be because younger children are least capable of hygienic behaviour themselves (Roberts 2000), and have longer‐lived infections and greater social contact, thereby acting as portals of infection into the household (Monto 1969). Additional benefit from reduced transmission from them to other members of the household is broadly supported by the results of other study designs where the potential for confounding is greater.Routine long‐term implementation of some of the interventions covered in this review may be problematic, particularly maintaining strict hygiene and barrier routines for long periods of time. This would probably only be feasible in highly motivated environments, such as hospitals. Many of the trial authors commented on the major logistical burdens that barrier routines imposed at the community level. However, the threat of a looming epidemic may provide stimulus for their inception.

Implications for researchPublic health measures and physical interventions can be highly effective to interrupt the spread of respiratory viral infections, especially when they are part of a structured and co‐ordinated programme that includes instruction and education, and when they are delivered together and with high adherence. Our review has provided important insights into research gaps that need to be addressed with respect to these physical interventions and their implementation and have been brought into a sharper focus as a result of the COVID‐19 pandemic. The 2014 WHO document 'Infection prevention and control of epidemic ‐ and pandemic‐prone acute respiratory infections in health care' identified several research gaps as part of their GRADE assessment of their infection prevention and control recommendations, which remain very relevant (WHO 2014). Research gaps identified during the course of our review and the WHO 2014 document may be considered from the perspective of both general and specific themes.A general theme identified was the need to provide outcomes with explicitly defined clinical criteria for acute respiratory infections (ARIs) and discrete laboratory‐confirmed outcomes of viral ARIs using molecular diagnostic tools which are now widely available. Our review found large disparities between studies with respect to the clinical outcome events, which were imprecisely defined in several studies, and there were differences in the extent to which laboratory‐confirmed viruses were included in the studies that assessed them. Another general theme identified was the lack of consideration of sociocultural factors that might affect adherence with the interventions, especially those employed in the community setting. A prime example of this latter point was illustrated by the observations of the use of masks versus mask mandates during the COVID‐19 pandemic. In addition, the cost and resource implications of the physical interventions employed in different settings would have important relevance for low‐ to middle‐income countries. Resources have been a major issue with the COVID‐19 pandemic, with global shortages of several components of PPE. Several specific research gaps related to physical interventions were identified within the WHO 2014 document and are congruent with many of the findings of this 2022 update, including the following: transmission dynamics of respiratory viruses from patients to healthcare workers during aerosol‐generating procedures; a continued lack of precision with regards to defining aerosol‐generating procedures; the safety of cohorting of patients with the same suspected but unconfirmed diagnosis in a common unit or ward with patients infected with the same known pathogen in healthcare settings; the optimal duration of the use of physical interruptions to prevent spread of ARI viruses; use of spatial separation or physical distancing (in healthcare and community settings, respectively) alone versus spatial separation or physical distancing with the use of other added physical interventions coupled with examining discrete distance parameters (e.g. one metre, two metres, or > two metres); the effectiveness of respiratory etiquette (i.e. coughing/sneezing into tissues or a sleeved bent elbow); the effectiveness of triage and early identification of infected individuals with an ARI in both hospital and community settings; the utility of entrance screening to healthcare facilities; use of frequent disinfection techniques appropriate to the setting (high‐touch surfaces in the environment, gargling with oral disinfectants, and virucidal tissues or clothing) alone or in combination with facial masks and hand hygiene; the use of visors, goggles or other eyewear; the use of ultraviolet light germicidal irradiation for disinfection of air in healthcare and selected community settings; the use of air scrubbers and /or high‐efficiency particulate absorbing filters and the use of widespread adherence with effective vaccination strategies.There is a clear requirement to conduct large, pragmatic trials to evaluate the best combinations in the community and in healthcare settings with multiple respiratory viruses and in different sociocultural settings. Randomised controlled trials (RCTs) with a pragmatic design, similar to the Luby 2005 trial or the Bundgaard 2020 trial, should be conducted whenever possible. Similar to what has been observed in pharmaceutical interventions where multiple RCTs were rapidly and successfully completed during the COVID‐19 pandemic, proving they can be accomplished, there should be a deliberate emphasis and directed funding opportunities provided to conduct well‐designed RCTs to address the effectiveness of many of the physical interventions in multiple settings and populations, especially in those most at risk, and in very specific well‐defined populations with monitoring of the adherence to the interventions. Several specific research gaps deserve expedited attention and may be highlighted within the context of the COVID‐19 pandemic. The use of face masks in the community setting represents one of the most pressing needs to address, given the polarised opinions around the world, and the increasing concerns over widespread microplastic pollution from the discarding of masks (Shen 2021). Both broad‐based ecological studies, adjusting for confounding and high quality RCTs, may be necessary to determine if there is an independent contribution to their use as a physical intervention, and how they may best be deployed to optimise their contribution. The type of fabric and weave used in the face mask is an equally pressing concern, given that surgical masks with their cotton‐polypropylene fabric appear to be effective in the healthcare setting, but there are questions about the effectiveness of simple cotton masks. In addition, any masking intervention studies should focus on measuring not only benefits but also adherence, harms, and risk compensation if the latter may lead to a lower protective effect. In addition, although the use of medical/surgical masks versus N95 respirators demonstrates no differences in clinical effectiveness to date, their use needs to be further studied within the context of a well‐designed RCT in the setting of COVID‐19, and with concomitant measurement of harms, which to date have been poorly studied. The recently published Loeb RCT conducted over a prolonged course in the current pandemic has provided the only evidence to date in this area (Loeb 2022).Physical distancing represents another major research gap which needs to be addressed expediently, especially within the context of the COVID‐19 pandemic setting as well as in future epidemic settings. The use of quarantine and screening at entry ports needs to be investigated in well‐designed, high‐quality RCTs given the controversies related to airports and travel restrictions which emerged during the COVID‐19 pandemic. We found only one RCT investigating quarantine, and no trials of screening at entry ports or physical distancing. Given that these and other physical interventions are some of the primary strategies applied globally in the face of the COVID‐19 pandemic, future trials of high quality should be a major global priority to be  conducted within the context of this pandemic, as well as in future epidemics with other respiratory viruses of less virulence.The variable quality and small scale of some studies is known from descriptive studies (Aiello 2002; Fung 2006; WHO 2006b), and systematic reviews of selected interventions (Meadows 2004). In summary, more high‐quality RCTs are needed to evaluate the most effective strategies to implement successful physical interventions in practice, both on a small scale and at a population level. It is very unfortunate that more rigorous planning, effort and funding was not provided during the current COVID‐19 pandemic towards high‐quality RCTs of the basic public health measures. Finally, we emphasise that more attention should be paid to describing and quantifying the harms of the interventions assessed in this review, and their relationship with adherence.

What's new

History

Protocol first published: Issue 4, 2006
Review first published: Issue 4, 2007

Notes

In Issue 1, 2010, the title of the review was changed from 'Interventions for the interruption or reduction of the spread of respiratory viruses' to 'Physical interventions to interrupt or reduce the spread of respiratory viruses'.

The original review was subsequently published as Jefferson T, Foxlee R, Del Mar C, Dooley L, Ferroni E, Hewak B, Prabhala A, Nair S, Rivetti A. Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review. BMJ 2008;336:77‐80 and Jefferson T, Del Mar C, Dooley L, Ferroni E, Al‐Ansary LA, Bawazeer GA, van Driel ML, Foxlee R, Rivetti A. Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review. BMJ 2009;339:b3675. DOI: 10.1136/bmj.b3675.

Acknowledgements

AcknowledgementsThis 2022 review update is funded by the National Institute for Health and Care Research (NIHR) ESP Incentive Award Scheme NIHR150879. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.We wish to acknowledge the late Chris del Mar for his substantial contributions as an author on previous versions of this review. We also thank Sarah Thorning for designing and updating searches from the 2011 publication to the 2020 publication. We thank Jessika Wejfalk for translating the funding source in a Danish trial in this 2022 update.The following people conducted the editorial process for this 2022 update:Sign‐off Editor (final editorial decision): Michael Brown (Michigan State University College of Human Medicine, USA).Managing Editor (selected peer reviewers, collated peer reviewer comments, provided editorial guidance to authors): Fiona Russell (Bond University, Australia).Contact Editor (assessed peer review comments and recommended an editorial decision): Allen Cheng (Monash University, Australia).Statistical Editor (provided comments): Teresa Neeman (Biological Data Science Institute, Australian National University, Australia).Copy Editor (copy‐editing and production): Heather Maxwell.Peer reviewers (provided comments and recommended an editorial decision):Clinical/content review: Roderick P. Venekamp.Consumer review: Janet Wale (Independent consumer representative).Methods review: Leslie Choi (Evidence Synthesis Development Editor, Cochrane Central Executive Team).

Competing interests

Declarations of interestLAA: has declared that they have no conflict of interest. GAB: reports working at King Saud University, Medical City, Riyadh, Saudi Arabia as clinical faculty in the College of Pharmacy, collaborating with pharmacy services to provide clinical pharmacy services in primary care clinics (non‐paid). EMB: has declared that they have no conflict of interest. JC: is an Information Specialist at the Cochrane Acute Respiratory Infections Group but was not involved in the editorial process for this review. JMC: has held or holds peer reviewed grants from the Canadian Institutes for Health Research (CIHR) on acute and primary care preparedness for COVID‐19 in Alberta, Canada and has received components of funding from a CIHR funded study via McMaster University for a randomised trial of medical masks versus N95 respirators for preventing COVID‐19 amongst healthcare workers. He has also been engaged in WHO funded studies using integrated human factors and ethnography approaches to identify and scale innovative IPC guidance implementation supports in primary care with a focus on low‐resource settings and using drone aerial systems to deliver medical supplies and PPE to remote First Nations communities during the COVID‐19 pandemic and was the primary local Investigator for a Staphylococcus aureus vaccine study funded by Pfizer for which all funding was provided only to the University of Calgary. He has received travel support from the Centers for Disease Control and Prevention (CDC) to attend an Infection Control Think Tank Meeting and from bioMerieux Canada to speak at a symposium on antimicrobial resistance co‐hosted by the University of Toronto and bioMerieux Canada. He also reports being a member and Chair of the WHO Infection Prevention and Control Research and Development Expert Group for COVID‐19 and reports being a member of the WHO Health Emergencies Programme (WHE) Ad‐hoc COVID‐19 IPC Guidance Development Group, both of which provide multidisciplinary advice to the WHO, for which no funding is received and from which no funding recommendations are made for any WHO contracts or grants. He reports declaring an opinion on topics in this review in Clinical Microbiology and Infection and Antimicrobial Resistance and Infection Control; reports being engaged as a co‐author on a randomised trial of medical masks versus N95 respirators for preventing COVID‐19 amongst healthcare workers published in the Annals of Internal Medicine in 2022 and mentioned in this current Cochrane Review, but no extraction or risk of bias assessment or data pooling or other assessment was undertaken by him nor will it be in any future updates. He has also been a member of the W21C since 2004 and served as its Medical Director from 2012‐2022. W21C is a not‐for‐profit healthcare systems research and innovation initiative based in the University of Calgary’s O'Brien Institute for Public Health and the Calgary Zone of Alberta Health Services. He reports working as an Infectious Diseases Consultant at Alberta Health Services, Calgary, Canada. LD: is a Managing Editor at the Cochrane Acute Respiratory Infections Group but was not involved in the editorial process for this review. EF: has declared that they have no conflict of interest. PG: reports a grant from the National Health and Medical Research Council, Australia. TH: is a member of the Cochrane Stroke Group Editorial Board but was not involved in the editorial process for this review. TJ: reports declaring an opinion on the topic of the review in articles for popular media. TJ is an Editor at the Cochrane Acute Respiratory Infections Group but was not involved in the editorial process for this review. See full statement here: https://restoringtrials.org/competing-interests-tom-jefferson/ MAJ: reports a grant from the National Institute for Health Research, UK. MAJ is Co‐ordinating Editor at the Cochrane Acute Respiratory Infections Group but was not involved in the editorial process for this review. MLvD: reports being a primary care panel member for the National COVID‐19 Clinical Evidence Taskforce, Australia. MLvD is Deputy Co‐ordinating Editor at the Cochrane Acute Respiratory Infections Group but was not involved in the editorial process for this review.

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Attribution. Tom Jefferson, Liz Dooley, Eliana Ferroni, Lubna A Al-Ansary, Mieke L Driel, Ghada A Bawazeer et al.. Physical interventions to interrupt or reduce the spread of respiratory viruses. The Cochrane Database of Systematic Reviews (2023);2023(1). doi:10.1002/14651858.CD006207.pub6 Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration. Licensed under CC BY 4.0. Reproduced from the open-access article via Europe PMC (PubMed 36715243). Text, tables and references reproduced from the open-access article; figures and images are not reproduced and no wording was changed.

About this article

Journal
The Cochrane Database of Systematic Reviews
Year
2023
Licence
CC BY 4.0
Source
Europe PMC
PubMed
36715243
Field
Immunology

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