key: cord-267699-h7ftu3ax
authors: MacIntyre, C. Raina; Chughtai, Abrar Ahmad
title: A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS
date: 2020-04-30
journal: Int J Nurs Stud
DOI: 10.1016/j.ijnurstu.2020.103629
sha: 
doc_id: 267699
cord_uid: h7ftu3ax

BACKGROUND: The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. RESULTS: A total of 19 randomised controlled trials were included in this study – 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. CONCLUSION: The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.

The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally.

Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public.

A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms.

A total of 19 randomised controlled trials were included in this study -8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently.

Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts.

The study suggests that community mask use by well people could be beneficial, particularly for COVID -19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift.

The use of personal protective equipment for coronavirus disease (COVID-19) has been controversial, with differing guidelines issued by different agencies (1) . Coronavirus disease is caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), a beta-coronavirus, similar to severe acute respiratory syndrome coronavirus2 (SARS CoV) (1). Seasonal alpha and beta coronaviruses cause common colds, croup and broncholitis. The transmission mode of coronaviruses in humans is similar, thought to be by droplet, contact and sometimes airborne routes (2) (3) (4) . The World Health Organization recommends surgical mask for health workers providing routine care to a coronavirus disease patient (5), whilst the US Centers for Disease Control and Prevention recommend a respirator (6) . Most authorities are recommending that community members not wear a mask, and that a mask should only be worn by a sick patient (also referred to as source control) (7) . There are more randomised controlled trials of community use of masks in well people than studies of the use by sick people (source control). The aim of this study was to review the randomised controlled trials evidence for use of masks and respirators by the community, health care workers and sick patients for prevention of infection.

We searched Medline and EmBase for clinical trials on masks and respirators using the key words "mask", "respirator", and "personal protective equipment". The search was conducted between 1 March to April 17 2020 and all randomised controlled trials published before the search date were included. Two authors (CRM and AAC) reviewed the title and abstracts to identify randomised controlled trials on masks and respirators. We also searched relevant papers from the reference lists of previous clinical trials and systematic reviews. Studies that were not randomised controlled trials, were about anaesthesia, or not about prevention of infection were excluded. Animal studies, experimental and observational epidemiologic studies were also excluded. Studies published in English language were included.

We found 602 papers on Medline and 250 on Embase. 820 papers were excluded by title and abstract review. Full texts were reviewed for 32 papers and 18 were selected in this review. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria (8) .

In general, the results show protection for healthcare workers and community members, and likely benefit of masks used as source control. We found eight clinical trials (9-16) on the use of masks in the community (Table 1 ). In the community, masks appear to be more effective than hand hygiene alone, and both together are more protective (9, 12) . However, the randomised controlled trials which measured both hand hygiene and masks measured the effect of hand hygiene alone, but not of masks alone (9, 12, 16) . Masks were only examined in combination with hand hygiene. Therefore the protective effect of masks and hand hygiene combined could be due to both interventions together, or the effect of masks alone. The use of hand hygiene alone in these trials was not effective. In more than one trial, interventions had to be used within 36 hours of exposure to be effective (9, 15, 16) .

To date, six randomised controlled trials (17) (18) (19) (20) (21) (22) has been conducted on the use of masks and/or respirators by healthcare workers in health care settings ( Table 2 ). The healthcare workers trials (Table 2) used different interventions and different outcome measures, and one was in the outpatient setting. A Japanese study had only 32 subjects, and likely was underpowered to find any difference between masks and control (18) . Two North American trials of masks and respirators against influenza infection found no difference between the arms, but neither had a control arm to differentiate equal efficacy from equal inefficacy (17, 22) . Without a control group to determine rates of influenza in unprotected healthcare workers, neither study is able to determine efficacy if no difference was observed between the two interventions. A serologic study showed that up to 23% of unprotected healthcare workers (a rate identical to that observed in Loeb the trial, which also used serology) contract influenza during outbreaks (23) , which suggests lack of efficacy. Studies of nosocomial influenza generally find lower influenza attack rates in unprotected healthcare workers than observed in the Loeb trial (24) .

Further problems with this study are that the majority of subjects were defined as having influenza on the basis of serological positivity (22) . The 10% seroconversion to pandemic H1N109 (with no pandemic virus isolation or positive PCR) observed in the trial, suggests that pandemic H1N109 was circulating in Ontario before April 2009, which is unlikely. The overall flu rate was 38%, higher than the expected attack rate in a pandemic (22) . The majority of subjects defined as having influenza were by serology.

A serological definition of influenza can be affected by vaccination. The authors claim they excluded influenza vaccinated subjects in the outcome, but according to Figure 1 , these subjects (130 in total) are included in the analysis. If they had been excluded and even if no other subjects were excluded, the total analysed would be 348, which is lower than the 422 subjects analysed (22) . These 130 vaccinated subjects should have been excluded entirely from the analysis. The vaccination status of subjects with seropositivity is not provided in the paper, but it appears people with positive serology due to vaccination may have wrongly been counted as influenza cases (22) .

In both the North American trials, the intervention comprised wearing the mask or respirator when in contact with recognized ILI or when doing a high risk procedure, which is a targeted strategy (17, 22) . One was in an outpatient setting. (17) We conducted a randomised controlled trial comparing the targeted strategy tested in the two North American studies, with the wearing of respiratory protection during an entire shift, and showed efficacy for continual (but not targeted) use of a respirator (19) . The study also did not show efficacy for a surgical mask worn continually, and therefore no difference between a surgical mask and targeted use of a respirator (19) , which is consistent with the findings of the North American trials (17, 22) . In summary, the evidence is consistent that a respirator must be worn throughout the shift to be protective. Targeted use of respirators only when doing high risk procedures and medical mask use is not protective. Another randomised controlled trial we conducted in China showed efficacy for continual use of a respirator, but not for a mask, and also found fit-testing of the respirator did not affect efficacy (20) .

However, this may be specific to the quality of the tested product, and is not generalisable to other respirators -fit testing is a necessary part of respirator use (25) .

For healthcare workers, there is evidence of efficacy of respirators if worn continually during a shift, but no evidence of efficacy of a mask (19, 20) . For hospitals where COVID-19 patients are being treated, there is growing evidence of widespread contamination of the ward environment, well beyond 2 meters from the patient, as well as aerosol transmission (2, 26, 27) . Several studies have found SARS-CoV-2 on air vents and in air samples in intensive care units and COVID-19 wards (26, 28, 29) , and an experimental study showed the virus in air samples three hours after aerosolization (30). The weight of this evidence and the precautionary principle(31, 32), favors respirators for healthcare workers. We showed lower rates of infection outcomes in the medical mask arm compared to control, but the difference was not significant (20) . It could be that larger trials are needed to demonstrate efficacy of a mask, but any protection is far less than from a respirator. A trial we conducted in Vietnam of 2-layered cotton cloth masks compared to medical masks showed a lower rate of infection in the medical mask group, and a 13 times higher risk of infection in the cloth mask arm (21) . The study suggests cloth masks may increase the risk of infection (21), but may not be generalizable to all home-made masks. The material, design and adequacy of washing of cloth masks may have been a factor (33) . There are no other randomised controlled trial of cloth masks published, but if any protection is offered by these it would be less than even a medical mask. Table 3 shows the trials of source control. There were five randomised controlled trials identified of masks used by sick patients (34) (35) (36) (37) . One was an experimental study of 9 influenza patients, which did not measure clinical endpoints (34) . Participants with confirmed influenza coughed onto a petri dish wearing a N95 respirator or a mask. No influenza grew on the medium. A trial of 105 sick patients wearing a mask (or no mask) in the household found no significant difference between arms (36). However, the trial was terminated prematurely and did not meet recruitment targets, so was probably underpowered. One randomised controlled trial was conducted among Hajj pilgrims, with both well and sick pilgrims wearing masks, and low rates of ILI were reported among contact of mask pilgrims (37) . Our randomised controlled trial is the largest available, and studied 245 patients randomised to mask or control (35) . Compliance was suboptimal in the mask group and some controls wore masks. The intention to treat analysis showed no difference, but when analysed by actual mask use, the rate of infection in household contacts was lower in those who wore masks (35) . A trial with an experimental design was published in April 2020, examining a range of viruses including seasonal human coronaviruses (38) . This showed that coronaviruses are preferentially found in aerosolized particles compared to large droplets, and could be expelled by normal tidal breathing. Wearing a surgical mask prevented virus from being exhaled.

There are more randomised controlled trials of community use of masks in well people (9) (10) (11) (12) (13) (14) (15) (16) than studies of the use by sick people (also referred to as "source control"), and these trials are larger than the few on source control (34) (35) (36) . The evidence suggests protection of masks in high transmission settings such as household and college settings, especially if used early, if combined with hand hygiene and if wearers are compliant (9, (12) (13) (14) (15) (16) . If masks protect in high transmission settings, they should also protect in crowded public spaces, including workplaces, buses, trains, planes and other closed settings. The trial which did not show efficacy used influenza as the outcome measure (10) , which is a rare outcome, so requires a larger sample size for adequate power and may have been underpowered.

For healthcare workers, the only trials to show a difference between respirators and masks demonstrated efficacy for continuous use of a respirator through a clinical shift, but not masks (19, 20) . The two trials which showed no difference are widely cited as evidence that masks provide equal protection as respirators (17, 22) . However, without a control arm, the absence of difference between arms could reflect equal efficacy or inefficacy, and it is not possible to draw any conclusions about efficacy. The high rates of influenza in the Loeb trial suggest equal inefficacy, and further, there were likely misclassified outcomes in the trial by inclusion of seropositive, vaccinated healthcare workers, which would have biased the results (22) . The outpatient setting in the US trial may have had lower exposure risk than the inpatient setting of other trials. (17) In both the North American trials, the intervention comprised wearing the mask or respirator when in contact with recognized ILI or when doing a high risk procedure (17, 22) . The underlying assumption that the majority of infections in healthcare workers occur during self-identified high-risk exposures is not supported by any evidence. It assumes healthcare workers can accurately identify when they are risk in a busy, clinical setting, when the majority of infections may occur when healthcare workers are unaware of the risk (such as when walking through a busy emergency room or ward where aerosolized virus may be present). Conversely, infections could occur outside the workplace. This could explain the lack of difference if there was no actual efficacy of either arm and if much of the infection occurs in unrecognised situations of risk either within or outside the workplace.

In practice, hospital infection control divides infections into droplet or airborne spread, and recommends droplet (mask) or airborne (respirator) precautions accordingly (39) . In a pooled analysis of both healthcare worker trials, we showed that continual use of a respirator is more efficacious in protecting healthcare workers even against infections assumed to be spread by the droplet route (39) . Medical masks did not significantly protect against viral, bacterial, droplet or other infection outcomes. However, the summary odds ratio for masks was less than one, which suggests a low level of protection. Targeted use of respirator protected against bacterial and droplet infections, but not against viral infections, suggesting viral infections may be more likely to be airborne in the hospital setting (39) .

The five available studies of mask use by sick patients suggest a benefit, but are much smaller trials than the community trials, two without clinical endpoints, and with less certainty around the findings (34) (35) (36) (37) . Only 3/5 trials examined clinical outcomes in close contacts (35) (36) (37) .

Many systematic reviews have been conducted on masks, respirators and other PPE in past (40) (41) (42) (43) (44) (45) (46) (47) (48) (49) . These reviews generally examined multiple interventions (e.g. masks and hand hygiene etc), often combined different outcome measures that were not directly comparable and were inconclusive. Moreover, most of these reviews did not include more recent randomised controlled trials (17, 21) . This systematic review only focuses on masks and respirators and contains all new studies.

In summary, there is a growing body of evidence supporting all three indications for respiratory protectioncommunity, healthcare workers and sick patients (source control). The largest number of randomised controlled trials have been done for community use of masks by well people in high-transmission settings such as household or college settings. There is benefit in the community if used early, and if compliant. They also found no evidence of efficacy of hand hygiene or health education, suggesting mask use is more protective than hand hygiene.

Respirators protect healthcare workers if worn continually, but not if worn intermittently in self-identified situations of risk. This supports the suggestion that the health care environment is a risk to healthcare workers even when not doing aerosol generating procedures or caring for a known infectious patient. For COVID-19 specifically, the growing body of evidence showing aerosolisation of the virus in the hospital ward highlights the risk of inadvertent exposure for healthcare workers and supports the use of airborne precautions at all times on the ward (26, 28, 29) . Further, the rule of 1-2 m of spatial separation is not based on good evidence, with most research showing that droplets can travel further than 2m, and that infections cannot be neatly separated into droplet and airborne (39, 50) . In the UK, one healthcare trust found almost one in five healthcare workers to be infected with COVID-19 (51) . The deaths of healthcare workers from COVID-19 reflect this risk (52) . The use of masks by sick people, despite being the WHO's only recommendation for mask use by community members during COVID-19 pandemic, is supported by the smallest body of evidence. Source control is probably a sensible recommendation given the suggestion of protection and given specific data on coronaviruses showing protection (38) . It may help if visitors and febrile patients wear a mask in the healthcare setting, whether in primary care or hospitals. Universal face mask use is likely to have the most impact on epidemic growth in the community, given the high risk of asymptomatic and pre-symptomatic transmission (53) . 

Research Fellowship) and Sanofi currently. She has received funding from 3M more than 5 years ago for face mask research.

Abrar Ahmad Chughtai had testing of filtration of masks by 3M for his PhD more than 5 years age. 3M products were not used in his research. He also has worked with CleanSpace Technology on research on fit testing of respirators (no funding was involved). 

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