Abstract

Clinicians and policymakers recommend preventive measures, including use of respiratory protective devices, to reduce the risk for coronavirus disease 2019 (COVID-19), the disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is thought that SARS-CoV-2 is spread primarily through contact and large respiratory droplets, but evidence also indicates potential transmission by fine respiratory aerosols (1). Several types of respiratory protective devices (collectively referred to as “face masks”) are available (2). Disposable N95 and equivalent respirators are fitted devices that have been tested to achieve very efficient filtration of small airborne particles, including aerosols. Surgical or medical masks (hereafter referred to as “surgical masks”) are loose-fitting, create a physical barrier, block larger particles, and are fluid-resistant. Cloth masks are nonmedical face coverings that vary with regard to filtration and fluid resistance depending on the material used, the number of layers, and fit. Single-use N95 and equivalent respirators provide higher respiratory protection than surgical masks (3), but shortages have been reported (4). Extended use and reuse of N95 respirators have been tested in laboratory settings (5), but clinical effectiveness and safety are uncertain (5, 6).

This living rapid review addresses the comparative effectiveness of face masks in community and health care settings for prevention of SARS-CoV-2 infection and associated COVID-19 disease, and the effectiveness and safety of mask reuse. This report will be used by the American College of Physicians (ACP) to develop evidence-based practice points on mask use in different settings. Because evidence is limited on SARS-CoV-2, this review also includes evidence on SARS-CoV-1 (causing SARS-1) and Middle East respiratory syndrome coronavirus (MERS-CoV) (causing MERS) and other viral respiratory illness (including influenza and influenza-like illness).

Methods

Detailed methods are available in the full report (7). The key questions were developed with input from staff at ACP and the Agency for Healthcare Research and Quality (AHRQ), with input from the review authors.

Key Question 1a. What is the effectiveness and comparative effectiveness of respirators (N95 or equivalent), face masks (surgical), and cloth masks in addition to standard precautions in community and health care (high- or non–high-risk) settings for prevention of SARS-CoV-2 infection?

Key Question 1b. For SARS-CoV-1 or MERS-CoV infection?

Key Question 1c. For influenza, influenza-like illness, and other viral respiratory infection?

Key Question 2. What is the evidence for extended or reuse of N95 respirators for prevention of SARS-CoV-2, SARS-CoV-1, or MERS-CoV infection?

Owing to the urgent and ongoing nature of the COVID-19 pandemic, a rapid, living review approach was used (8). Rapid reviews utilize streamlined systematic review processes. For this review, modified methods included 1) a gray literature search limited to 1 website; 2) dual review of excluded abstracts only; 3) critical appraisal of observational studies not conducted by using a formal instrument; and 4) critical appraisal and data abstraction by a single reviewer, with verification by a second reviewer. Living reviews use methods for continually updating, as new evidence becomes available (9).

Results

Thirty-nine studies (33 867 participants), all addressing key question 1, met the inclusion criteria (19–50-51–57). Figure 1 summarizes the study selection process and number of included studies, by setting (community or health care) and study type. Twelve RCTs (19–21, 23, 24, 28–30, 37, 41, 48, 49) and 3 observational studies (31, 51, 54) were conducted in the community, and 6 RCTs (27, 34, 38–40, 46) and 18 observational studies (22, 25, 26, 32, 33, 35, 36, 42–45, 47, 50, 52, 53, 55–57) were conducted in HCWs (Supplement Tables 3 and 4). There were no RCTs on risk for coronavirus infections. For SARS-CoV-2, there were 2 cohort studies (52, 56). Eighteen observational studies addressed SARS-CoV-1 (25, 26, 31–33, 35, 36, 42–45, 47, 50, 51, 53–55, 57), and 1 cohort study addressed MERS-CoV (22). No death was recorded in any study. The RCTs were usually conducted during influenza season and evaluated the risk for nonspecific clinical respiratory illness, influenza-like illness, and laboratory-confirmed viral respiratory illness. Two Chinese-language studies were translated into English by a native Chinese speaker on the review team (36, 55).

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Figure 1.

Literature search and selection.

ILI = influenza-like illness; VRI = viral respiratory illness; MERS-CoV = Middle East respiratory syndrome coronavirus; SARS-CoV = severe acute respiratory syndrome coronavirus.

Two RCTs (27, 34) were randomized by individual participant; the remaining trials were randomized by clusters (households, university residence halls, tents during Hajj, hospitals, hospital wards, or outpatient settings). The number of participants ranged from 164 to 7687. The RCTs were conducted during influenza season, except for 2 RCTs of Hajj pilgrims staying in tents (21, 23). Two RCTs (34, 37) reported the incidence of laboratory-confirmed nonpandemic coronavirus infections, but 1 trial only reported 1 case (37). Four trials were conducted in the United States, 1 in Canada, 1 in Australia, 2 in Europe, 2 in Saudi Arabia, and 8 in Asia. Eleven RCTs were rated good-quality, and 7 were rated fair-quality (Supplement Table 5). Limitations of the fair-quality trials included baseline between-group differences and high attrition; one cluster RCT (23) did not adjust for cluster correlation. Blinding of participants to the mask and other interventions (for example, hand hygiene) was not possible.

The observational studies had important limitations (Supplement Table 4). All were retrospective and potentially susceptible to recall bias for determining mask use and other exposures. The studies were limited in their ability to measure and control for the amount and intensity of exposures. Six studies did not control for potential confounders. Of the 15 studies that did control for confounders, only 1 (33) evaluated correlations between masks and other infection control measures (such as gloves, gowns, goggles, or handwashing) to inform variable selection for model building. In the other studies that reported results from multivariate models, correlations between infection control measures and potential collinearity were not addressed.

Effectiveness of Masks

Key Question 1a: SARS-CoV-2

Community settings. No study evaluated masks for preventions of SARS-CoV-2 infections in community settings.

Health care settings. Two cohort studies evaluated mask use and risk for SARS-CoV-2 infection, but had important limitations (52, 56). One study (493 participants) of HCWs in higher- and lower-risk hospital units found N95 respirators to be associated with decreased infection risk versus no mask, but mask use was based on whether the HCW worked in a department in which masks were used, not on assessment of individual use (52). In addition, departments with N95 respirator use differed from departments that did not use N95 respirators in other infection control measures (such as handwashing and use of protective clothing) and exposure to patients with COVID-19. There were also few HCW cases and serious imprecision. The other study was small (37 participants) and evaluated HCWs with inadequate personal protective equipment during exposure to a patient with unrecognized SARS-CoV-2 infection (56). It reported 3 cases of SARS-CoV-2 infection in HCWs, resulting in very imprecise estimates.

Key Question 1b: SARS-CoV-1 and MERS-CoV

Community settings. Three observational studies (2857 participants) evaluated masks and SARS-1 risk in community settings (Supplement Table 4) (31, 51, 54). The studies did not compare mask types or provide details regarding mask type. Wearing a mask was associated with decreased risk for infection in persons without known SARS-1 contacts in 1 study (54) and in household contacts of patients with SARS-1 in 2 studies (Supplement Table 6) (31, 51).

Health care settings. Fifteen observational studies (3994 participants) evaluated the association between mask use by HCWs and risk for SARS-CoV-1 infection (25, 26, 32, 33, 35, 36, 42–45, 47, 50, 53, 55, 57), and 1 study (283 participants) (22) evaluated the association between mask use and MERS-CoV infection (Supplement Table 4). Five studies were conducted in high-risk settings, and the remainder in moderate-risk settings (Supplement Table 7, available at Annals.org); no study was low risk. The proportion of HCWs with close or direct contact with SARS-CoV-1 or MERS-CoV cases was high in studies that reported this information; use of personal protective equipment varied (Supplement Table 7).

Five observational studies (1208 participants) consistently found N95 respirators to be associated with decreased risk for SARS-CoV-1 infection versus surgical masks (sometimes described as “disposable” masks) in HCWs (Supplement Table 8) (25, 33, 35, 45, 57); all but 1 study (33) were conducted in high-risk settings. Results of 3 comparisons (1207 participants) involving an N95 respirator or surgical versus cloth mask and risk for SARS-CoV-1 in moderate-risk settings were somewhat inconsistent (33, 36, 55). The cloth mask material was cotton or not reported, and cloth masks were described as 12- or 16-layer masks, potentially reducing generalizability to the United States and other countries where cloth masks typically have far fewer layers.

Twelve observational studies (2998 participants) consistently found mask use associated with decreased risk for SARS-CoV-1 infection versus no use (Supplement Table 8) (33, 35, 36, 42–45, 47, 50, 53, 55, 57); of these, 8 specifically evaluated N95 respirators or surgical masks (33, 35, 36, 45, 47, 50, 55, 57). Results were consistent when studies were stratified by high- or moderate-risk setting (34, 45, 53, 57). Masks were associated with decreased risk for SARS-CoV-1 infection in multivariate models in 5 studies (33, 43, 47, 50, 55).

Four studies (626 participants) found more consistent mask use by HCWs to be associated with decreased risk for SARS-CoV-1 or MERS-CoV infection versus less consistent use (Supplement Table 8) (22, 32, 35, 43); of these, 3 specifically evaluated N95 or surgical masks (22, 32, 35) and 1 was in a high-risk setting (32). In 1 of the studies, consistent use of N95 respirators or surgical masks was associated with decreased infection risk in HCWs who had direct contact with SARS-1 patients, direct contact with non–SARS-1 patients, and no direct patient contact (32).

Key Question 1c: Influenza, Influenza-like Illness, and Other Viral Respiratory Illness

Community settings. Twelve RCTs (16 836 participants) evaluated masks in community settings (Table 1 and Supplement Table 3) (19–21, 23, 24, 28–30, 37, 41, 48, 49). The settings were households, university residence halls, and tents used by Hajj pilgrims. Masks were used by infected index cases (“source control”), household contacts of index cases, cases and contacts, or persons without specific contact with cases. All participants generally received education on preventing respiratory infection and hand hygiene. All of the trials compared a mask versus no mask; 1 trial also compared a mask versus a mask plus handwashing training (48).

Table 1. Randomized Controlled Trials of Masks for Prevention of Viral Respiratory Infection in Community Settings

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Only 1 RCT (290 participants) directly compared different mask types (37). It evaluated a P2 mask (Australian equivalent to an N95 respirator) versus a surgical mask in adult household contacts of children with influenza-like illness. There were no differences between either mask type versus no mask in infection outcomes, though estimates were imprecise. The RCT did not report cluster-adjusted risk estimate for the P2 versus the surgical mask, but the calculated (crude) unadjusted estimate was not statistically significant. Adherence to mask use was low, potentially reducing effectiveness (Supplement Table 9). In a multivariate analysis, adherence to either mask was associated with decreased risk for influenza-like illness (hazard ratio, 0.26 to 0.32).

Eight trials (6510 participants), including the trial described above, evaluated use of surgical masks within households with an influenza or influenza-like illness index case (child or adult) (24, 28–30, 37, 41, 48, 49). Compared with no masks, surgical masks were not associated with decreased risk for clinical respiratory illness, influenza-like illness, or laboratory-confirmed viral illness in household contacts when masks were worn by household contacts (30, 37, 48), index cases (24, 41), or both (28, 29, 49). However, some estimates were imprecise, mask-wearing adherence was limited (Supplement Table 9), and some crossover occurred. Two trials found no differences between surgical masks plus handwashing versus handwashing alone in risk for infections in household contacts of index cases (30, 48).

Two trials (2475 participants) of students living in university residence halls without specific contacts with cases also found no significant differences between a surgical mask versus no mask and risk for influenza-like illness (19, 20). Two trials (7851 participants) found that surgical masks, compared with no masks, were not associated with decreased risk for infections in Hajj pilgrims with or without an infected index case within the same tent (21, 23).

Health care settings. Six RCTs (9411 participants) evaluated mask use among HCWs in health care settings (Table 2 and Supplement Table 3) (27, 34, 38–40, 46). One was a pilot trial that reported adherence and harms but not effects on risk for infections (27). Of the other 5 trials, 4 compared an N95 respirator versus surgical mask (38–40, 46) and 1 (38) compared a surgical versus cloth mask (Table 2). Masks were generally used in addition to handwashing, though details on use of personal protective equipment (for example, eye protection, gowns, and gloves) were limited.

Table 2. Randomized Controlled Trials of Masks for Prevention of Viral Respiratory Infection in Health Care Settings

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Three RCTs (3532 participants) compared N95 respirators versus surgical masks in higher-risk settings (such as emergency departments, respiratory wards, pediatric wards, and intensive care units) (34, 39, 40). One trial (422 participants) found both N95 respirators and surgical mask to be associated with a very similar likelihood of a physician visit for acute respiratory illness (6.2% vs. 6.1%) (34). Two trials (3110 participants) found an N95 respirator to be associated with decreased risk for clinical respiratory illness, with absolute differences that ranged from –2.8% to –7.7% (39, 40).

In all 3 trials, there were few cases of influenza-like illness, resulting in imprecise estimates (34, 39, 40). For laboratory-confirmed viral respiratory infections, 1 trial (34) that did not require HCWs to have symptoms found no difference between an N95 respirator and a surgical mask in infection risk. In the other 2 trials, only symptomatic laboratory-confirmed viral respiratory infections were diagnosed; the number of cases was small, and estimates were imprecise. One trial reported no difference in the subgroup of laboratory-confirmed (not necessarily symptomatic) viral infections by nonpandemic coronaviruses but was underpowered for this outcome, with a total of 21 cases (34). The other 2 trials did not report nonpandemic coronavirus infections.

Two trials described above included 2 N95 respirator arms (39, 40). One trial found that the effects of an N95 respirator versus surgical mask on clinical respiratory illness were similar for fit-tested and non–fit-tested N95 respirators (4.6% vs. 3.3%) (39). The other trial found continuous use (at all times while working) of an N95 respirator to be associated with a small decrease in clinical respiratory illness risk versus intermittent use (only during high-risk procedures or barrier situations) of an N95 respirator (7.2% vs. 11.8%) (40).

One trial (1868 participants) of HCWs in higher-risk settings found a surgical mask to be associated with decreased risk for clinical respiratory illness, influenza-like illness, and laboratory-confirmed viral infections versus cloth masks, but estimates were imprecise and not statistically significant (38).

One trial of HCWs (2862 participants) in lower-risk outpatient settings found no differences between an N95 respirator and a surgical mask in risk for clinical respiratory illness, influenza-like illness, laboratory-confirmed viral illness, or laboratory-confirmed influenza (46).

Discussion

This rapid, living review summarizes the evidence on the comparative effectiveness and effectiveness for preventing coronavirus and other respiratory infections. Figure 2 is an evidence map summarizing the strength of evidence for key comparisons by setting and infection type (Supplement Table 10). The map shows that direct evidence on the comparative effectiveness of masks for preventing COVID-19 due to SARS-CoV-2 infection is lacking. Therefore, it was necessary to also consider evidence for other respiratory infections, though the applicability to COVID-19 is uncertain. In addition, the strength of evidence varied from moderate to insufficient; no comparison was graded high strength of evidence.

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Figure 2.

Masks for prevention of respiratory virus infection: evidence map.

* Only observational evidence was included for these infections.

† Only RCT evidence was included for these infections.

‡ N95 respirator or equivalent (for example, P2 mask).

In community settings, one RCT found no difference between N95 or equivalent respirators versus surgical masks in risk for noncoronavirus respiratory illness (37). The RCTs in community settings, typically conducted during influenza seasons, also did not indicate effectiveness of mask use versus no mask use for reducing viral respiratory infection risk, though mask compliance was suboptimal. Observational data on mask use effectiveness in community settings for preventing infections associated with epidemic coronaviruses were limited but suggest possible reduced risk for SARS-1. The difference in findings could be related to higher mask compliance in pandemic outbreak settings, greater effectiveness of masks for SARS-1, or residual confounding.

In HCWs, observational studies suggest that N95 masks might be associated with decreased risk for SARS-CoV-1 infection compared with surgical masks, and mask use in general appears to be associated with decreased risk for SARS-CoV-1 infection. All studies were conducted in high- or moderate-risk settings, with uncertain applicability to low-risk settings (those without direct care of infected patients). Review of RCTs indicates that N95 respirators and surgical masks are probably associated with similar risk for influenza-like illness and laboratory-confirmed viral infections in high- and low-risk settings. However, there was some inconsistency in effects of N95 respirators versus surgical masks on clinical respiratory infections in high-risk settings, with 1 trial (34) showing no difference in physician visits for respiratory illness and 2 trials (39, 40) showing N95 respirators to be associated with a small decrease in risk. The only trial comparing N95 respirators versus surgical masks in a low-risk (primary care) setting found no difference in risk for clinical respiratory illness (46). There was no evidence to address effects of extended or reuse of N95 respirators on infection risk; evidence on nonclinical outcomes (for example, measures of filtration, contamination, and mask failure) is summarized elsewhere (5).

Our findings are generally consistent with those of recent systematic reviews on mask use in community and health care settings that found N95 respirators and surgical masks to be associated with similar risk for influenza and influenza-like illness (58–62). It differs from prior reviews by considering both randomized trials and observational studies, evaluating mask use in community and health care settings, considering harms, comparing effects of consistent versus less consistent mask use, and including a more comprehensive set of relevant studies. We also implemented living review processes in order to incorporate new evidence on an ongoing basis. There was some overlap between this review and our living review on risk factors (including various types of personal protective equipment) for coronavirus infections in HCWs (12). This review differed from our prior review by including studies conducted in community settings, focusing on mask use, and including effects on noncoronavirus viral respiratory infections.

The evidence base has important limitations. As noted, the evidence on mask use and risk for SARS-CoV-2 infection is very sparse. In randomized trials, adherence to mask use was suboptimal, potentially reducing estimates of effectiveness compared with use during pandemic outbreaks, when adherence may be higher. Observational studies were retrospective, susceptible to recall bias and confounding, and did not address correlations between mask use and other infection prevention and control measures. Applicability of evidence on masks and risk for SARS-CoV-1, MERS-CoV, and other viral respiratory illness to SARS-CoV-2 is uncertain. The applicability of evidence on influenza and influenza-like illnesses to SARS-CoV-2 could be reduced owing to differential transmission dynamics, lower mask adherence, or limited use of other personal protective equipment (63).

The review process had limitations. In particular, we used streamlined rapid review methods for searching and selecting studies. We did not perform critical appraisal of observational studies by using a formal instrument, though key methodological limitations were highlighted. We included 1 non–peer-reviewed study (21), which could reduce data quality. Meta-analysis was not attempted owing to study limitations and heterogeneity in study designs, comparisons, and analyses.

Research is urgently needed to clarify the comparative effectiveness of masks for transmission of COVID-19 in community and health care settings; randomized trials are in progress (64, 65). Observational studies that prospectively measure mask use, other infection prevention and control measures (accounting for potential correlations), and exposures could supplement randomized trials. Given limitations in the supply of N95 respirators, understanding the effects of reuse or extended use of N95 respirators is a priority (66).

In conclusion, evidence on the effectiveness of masks for prevention of respiratory infection is stronger in health care than community settings. Use of N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain.

Biography

Footnotes

References