key: cord-0807515-ov0greaf authors: Nanda, Akriti; Hung, Ivan; Kwong, Ava; Man, Vivian Chi‐Mei; Roy, Pankaj; Davies, Lucy; Douek, Michael title: Efficacy of surgical masks or cloth masks in the prevention of viral transmission: Systematic review, meta‐analysis, and proposal for future trial date: 2021-02-09 journal: J Evid Based Med DOI: 10.1111/jebm.12424 sha: 8cd705bf1e4bbf1d1a2d5aaeced65f70ea84cf11 doc_id: 807515 cord_uid: ov0greaf OBJECTIVE: Recommendations for widespread use of face mask, including suggested type, should reflect the current published evidence and concurrently be studied. This review evaluates the preclinical and clinical evidence on use of cloth and surgical face masks in SARS‐CoV‐2 transmission and proposes a trial to gather further evidence. METHODS: PubMed, EMbase, and the Cochrane Library were searched. Studies of SARS‐CoV‐2 and face masks and randomized controlled trials (RCTs) of n ≥ 50 for other respiratory illnesses were included. RESULTS: Fourteen studies were included in this study. One preclinical and 1 observational cohort clinical study found significant benefit of masks in limiting SARS‐CoV‐2 transmission. Eleven RCTs in a meta‐analysis studying other respiratory illnesses found no significant benefit of masks (±hand hygiene) for influenza‐like‐illness symptoms nor laboratory confirmed viruses. One RCT found a significant benefit of surgical masks compared with cloth masks. CONCLUSION: There is limited available preclinical and clinical evidence for face mask benefit in SARS‐CoV‐2. RCT evidence for other respiratory viral illnesses shows no significant benefit of masks in limiting transmission but is of poor quality and not SARS‐CoV‐2 specific. There is an urgent need for evidence from randomized controlled trials to investigate the efficacy of surgical and cloth masks on transmission of SARS‐CoV‐2 and user reported outcomes such as comfort and compliance. evidence, they recommend cloth masks for the public to control SARS-CoV-2 and to preserve surgical and FFP3 respirators for medical settings. 2 Any recommendation for widespread use of face masks, including type, should reflect the current published evidence whilst identifying gaps where evidence is lacking and plans research to fill them. This paper systematically reviews the published preclinical and clinical evidence for the use of face masks in SARS-CoV-2 and proposes a trial to holistically evaluate the evidence for masks in SARS-CoV-2. The underlying logic behind use of face masks is that they are a physical barrier retaining the droplets, aerosols and particles, by which SARS-CoV-2 spreads. Droplets spread continuously in the flow of air a person creates when breathing and talking that can travel up to 8 m. 3 A recent study by the University of Edinburgh found all face mask materials, except those with valves, reduced the front flow of air from a modeled human by more than 90%. 4 A study published in Nature Medicine showed this barrier effect of surgical masks also significantly reduced detection of influenza, coronavirus and rhinovirus virus RNA in respiratory droplets and coronavirus RNA in aerosols of exhaled breaths of participants with laboratory confirmed illnesses. 5 SARS-CoV-2 has presymptomatic spread with carriers having maximal viral shedding prior to being ill, 6 a prolonged incubation period with a significant proportion of asymptomatic carriers capable of shedding the virus. 7 These transmission dynamics support precautionary universal masking of the public to prevent transmission. Cloth masks are currently promoted by many governments to preserve surgical masks, but evidence of their equivalence to surgical masks is conflicting. One study comparing homemade cloth masks with additional kitchen roll versus N95 masks and surgical masks reported comparable efficacy of 95.15% versus 99.98% and 97.14%, respectively, in blocking avian influenza aerosols. 8 However, another study comparing the number of microorganisms isolated from a cough, found cotton cloth masks were 1/3rd as effective as surgical masks. Cloth masks still significantly reduced the number of microorganisms compared to the control of no mask. 9 Cloth masks are not fluid resistant so liable to get damp with prolonged use, which may reduce their barrier function. Their use in SARS-CoV-2 is important to study to inform public and manufacturing guidance given the burgeoning face mask market. Indirect evidence that face masks may be an effective source control tool for SARS-CoV-2 comes from observations from surveys of household contacts of index cases and case number trends in different countries. Li et al 10 found in 105 cases and 392 household contacts, the secondary attack rate in households where the index patients quarantined upon symptom development (n = 14 used masks, dined separately, and distanced within the home). A study in Taiwan that found universal masking and hand-hygiene during the COVID-19 pandemic resulted in a 50% decline of infectious respiratory diseases compared to previous years. 11 Similarly, countries that practiced tight infectious control measures including universal masking and social distancing including China, Vietnam and South Korea and had significantly fewer cases and mortality, when compared to countries with more lax health precaution measures. 12 These findings give rationale to the policy of universal face masks for the general public but evidence from direct study is important evaluate efficacy of such policies to inform future strategy in the ongoing SARS-CoV-2 pandemic. A systematic review of the literature was performed using PubMed, To enter the analysis, studies were required to fulfill one of the following criterion: any preclinical directly studying SARS-CoV-2 transmission and mask use, any published in practice studies (RCTs or observational studies) of mask use by humans in SARS-CoV-2, any RCT with more than 50 participants of face mask use compared with no mask or any RCT of cloth mask use compared with any control in any respiratory viral illness. Studies that failed to fulfill the inclusion criteria or studies where the outcomes of interest were not reported or if it was impossible to calculate these from the published reports were excluded. Registered trials with no results were not included in the analysis but mentioned in the discussion. Each study was evaluated for inclusion or exclusion from the review and the following data were extracted: first author, year of publication, study design, number of participants, location, duration, disease/outcome studied, intervention and control, methods of study, compliance to interventions, and other significant details. One reviewer (AN) extracted data for all selected studies using RevMan software 5.0. 13 The accuracy of the extracted data was verified by the second reviewer (MD). For assessing the risk of bias (ROB), the OHAT risk of bias tool 14 was used for preclinical studies, ROBINS-1 tool for nonrandomized studies 15 and Cochrane's risk of bias tool for RCTs. 16 RevMan 5.2 software was used for the quantitative analyses. Dichotomous outcomes were extracted as numerators and denominators and summarized using risk ratios (RRs) and 95% confidence intervals (CIs). RCTs were grouped by the outcome they assessed (laboratory confirmed respiratory virus and influenza like illness) and based on whether the intervention was a face mask alone or with hand hygiene. The random-effects model was used to calculate the pooled outcome due to the studies sampling dissimilar populations and heterogeneity in the studies. A total of 1499 studies were found in the search ( Figure 1 ); after title, abstract and full text screening 14 studies were included in the review and 11 in the meta-analysis. Of the studies found, there was 1 preclinical and 1 clinical study directly studying mask use in transmission of SARS-CoV-2, 11 randomized controlled trials studying transmission of other respiratory illnesses, and 1 randomized controlled trial comparing surgical and cloth masks in the prevention of respiratory illness. The preclinical study used hamsters infected with SARS-CoV2 placed in cages adjacent to healthy hamsters to investigate noncontact transmission of SARS-CoV-2. 17 A fan was used to transmit the virus between the cages. In the control (no barrier between the cages), hamsters were infected at a 66.7% rate after 7 days (10/15) compared to 16 .7 (2/12) when a barrier of surgical face masks was put on both cages. The rate rose to 25% (6/24) when masks were only placed on the cage of healthy hamsters. There was some concern over confounding bias that the authors could not be certain of the exact source of transmission and could not rule out transmission amongst hamsters in the same cage. They were unable to keep experimental conditions identical across study groups; for example, the speed of the unidirectional airflow could not be unified when the surgi-cal mask partitions were installed-though this may simulate airflow when surgical masks are worn in practice. The risk of bias is shown in Figure 2 . We found one other preclinical study in humans directly studying medical and cloth mask use in SARS-CoV-2; 18 however this study was retracted 19 due to errors in analysis and therefore not included in our analysis. The clinical study was a nonrandomized retrospective observational cohort study. 20 The For trials for surgical mask use in preventing any other respiratory illness; after title and abstract and full text screening. Eleven RCTs [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] were selected (see Table 1 for study characteristics and Figures 4 and 5 for summary of risk of bias). When combined, the 10 RCTs that looked at face mask use with or without hand hygiene (FM ± HH) had moderate heterogeneity that was significant (I 2 = 54%, P = .02) ( Figure 6 ). In the random-effects model, no significant difference was demonstrated between mask and no mask groups for the outcome of laboratory confirmed respiratory viral illness (RR = 0.99, 95% CI: 0.98-1.01). For face masks alone ( Figure 7 ) there was moderate heterogeneity that was not significant (I 2 = 53%, P = .05), among the seven RCTs. In the random-effects model, there was no difference demonstrated between mask and no mask groups for the outcome of laboratory confirmed respiratory viral illness (RR = 1.00, 95% CI: 0.98-1.02). For face masks and hand hygiene (FM+HH) as the intervention ( Figure 8 ) there was moderate heterogeneity that was not significant (I 2 = 40%, P = .14) among the six RCTs. and Adults (Aerokyn Masques) When combined, the 11 RCTs that looked at FM ± HH there was significant heterogeneity (I 2 = 84%, P < .001) ( Figure 9 ). In the random-effects model there was no differ- For FM alone ( Figure 10 ) there was substantial heterogeneity that was significant (I 2 = 72%, P < .0008), amongst the eight RCTs. In the random-effects model, there was no significant difference demonstrated between mask and no mask groups for the outcome of laboratory confirmed respiratory viral illness (RR = 1.03, 95% CI: 0.97-1.09). For FM+HH (Figure 11) , there was substantial heterogeneity that was significant (I 2 = 81%, P < .0001) amongst the six RCTs. The random effects model demonstrated no significant benefit of masks plus hand hygiene in lowering influenza like symptoms; however, the studies have significant clinical heterogeneity (RR = 1.02, 95% CI: 0.96-1.08). The quality of evidence was moderate or low quality primarily due to risk of bias, small effect magnitudes, substantive inconsistency of the results and differences in the population groups and study designs included in the various studies. Therefore, confidence in the effect estimate is limited and the true effect may be substantially different from the estimate of the effect. A funnel plot was done for all studies using the influenza like illness outcome for FM ± HH versus control, which shows that publication bias cannot be ruled out. One cluster RCT 32 The published preclinical body of evidence that directly investigates SARS-CoV-2 and masks is limited. This is likely due to the difficult of directly studying SARS-CoV-2 and masks in an experimental set up and push for clinical data. Overall, the preclinical study was of high quality The study quality is low with confounding factors such as adherence, affecting the overall conclusion. Although adherence to mask use makes the results difficult to interpret, it may be that this is the reality of how effective this intervention would be in real world application. However, results from observational studies in the time of SARS, suggest adherence was better than the influenza trials as the perceived threat is greater. 35, 36 Behavioral studies support the idea that individuals were more likely to wear face masks when the perceived susceptibility and severity of being afflicted with life-threatening diseases was high. 37 None of the studies look at the unintended harms of the intervention, for example, discomfort, reactive dermatitis, distress, breathing difficulties, etc, which are important as they may affect adherence to the intervention. All but two of these studies 21, 22 identified index cases and studied secondary attack rates, which does not account for spread of the respiratory virus before randomization. The other two studies looked at all respiratory viral rates in a student cohort over several months. The studies that masked index cases [23] [24] [25] [26] [27] [28] [29] [30] [31] can inform how masking both the wearer and the contact can limit transmission. It is difficult to elucidate whether the effect is due to infection prevention in someone protecting themselves from others, or others from themselves. None of the studies focused on SARS-CoV2 or focus on beta-coronaviruses so the generalizability in the current pandemic is limited. One c-RCT 32 found rates of all infection outcomes (ILI and laboratory confirmed) were higher in the cloth mask arm compared with the surgical mask arm. The authors could not determine whether this is because of reduced benefit of the cloth masks in comparison to surgical masks or a detrimental effect of cloth masks because they did not have enough non mask wearers in the control group. The authors hypothesize that the poor performance of cloth masks could be due to their inferior filtration potential and the act of doffing, washing, and reusing the mask. The question arises whether we should be wary of the message that cloth masks offer equal protection in transmission as surgical masks without evidence to support its use. The current recommendation is also based resource allocation and prioritizing high risk such as healthcare settings. With more evidence to support the benefits of surgical mask, efforts to increase the supply of surgical masks and education on its proper use may be more impactful. Compliance was similar in both arms of the study (56.8% with cloth masks and 56.6% with surgical masks). Although in a healthcare setting in nonpandemic times, this suggests adherence to either mask will be similar. However, there is a trend of media outlets purporting the "comfiest" masks suggesting comfort is important for the general public. 38, 39 An overview of 84 articles 40 found surgical masks negatively impacted thermoregulation in humans thus making them hard to wear constantly. This highlights the need to study the side effects and user reported outcomes of each mask type and whether they affect compliance. A compromise in efficacy for gain in user-comfort and compliance may be beneficial in terms of public health. The existing evidence is poor and highlights the need for further study. We propose a randomized controlled trial where patients are consented, randomized by cluster (eg, by workplace). To account for varying government guidance across countries on face masks mandates; the arms of randomization should be a control of normal behavior according to the authority's recommendations mask and experimental arms of normal behavior plus a face mask (each arm with a different type of face mask). An alternative method of randomizing would be to cluster household contacts of a confirmed index case of SARS-CoV-2. Once a patient had confirmed SARS-CoV-2, their household members will receive either surgical masks, cloth face masks, or education on other infection control methods. All households will be asked to follow current recommended advice of isolating the index case and minimizing contact. All participants will be asked to self-report their symptoms with interval testing of SARS-CoV-2 RT-PCR by nasopharyngeal swab to measure the secondary attack rates. Participants should be tested for antibodies before the start date and after study completion. The participants should also be asked to report on user reported outcomes such as comfort, effects on quality of life and adherence to the masks. If both masks are found to be equivalent in safety and efficacy, then the findings on which mask type is more acceptable to wear to the participant and if this affects compliance will be important outcomes to assess. In this way, a definitive answer with a high powered RCT can answer whether surgical mask or use of cloth face covering can limit SARS-CoV-2 transmission in community applications. As the world comes out of lockdown, now is the time for a randomized trial to establish the evidence of cloth and surgical masks in the prevention of transmission in SARS-CoV-2. The available preclinical findings limited clinical and indirect evidence suggests biological plausibility that face masks may reduce the spread of SARS-CoV-2. 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Akriti Nanda https://orcid.org/0000-0002-7333-2730