key: cord-0703230-upiu3e2d
authors: Collins, Andrew P.; Service, Benjamin C.; Gupta, Sunny; Mubarak, Naser; Zeini, Ibrahim Mamdouh; Osbahr, Daryl C.; Romeo, Anthony A.
title: N95 respirator and surgical mask effectiveness against respiratory viral illnesses in the healthcare setting: A systematic review and meta‐analysis
date: 2021-10-28
journal: J Am Coll Emerg Physicians Open
DOI: 10.1002/emp2.12582
sha: ee671573677b1ce86e8b4c3cedee7e7321809544
doc_id: 703230
cord_uid: upiu3e2d

OBJECTIVE: To examine the results, level of evidence, and methodologic quality of original studies regarding surgical mask effectiveness in minimizing viral respiratory illness transmission, and, in particular, the performance of the N95 respirator versus surgical mask. METHODS: Meta‐analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines with use of PubMed, MEDLINE, and the Cochrane Library databases. RESULTS: Eight studies (9164 participants) were included after screening 153 articles. Analyses showed statistically significant differences between N95 respirator versus surgical mask use to prevent influenza‐like‐illness (risk ratio [RR] = 0.81, 95% confidence interval [CI] = 0.68–0.94, P < 0.05), non‐influenza respiratory viral infection (RR = 0.62, 95% CI = 0.52–0.74, P < 0.05), respiratory viral infection (RR = 0.73, 95% CI = 0.65–0.82, P < 0.05), severe acute respiratory syndrome coronavirus (SARS‐CoV) 1 and 2 virus infection (RR = 0.17, 95% CI = 0.06–0.49, P < 0.05), and laboratory‐confirmed respiratory viral infection (RR = 0.75, 95% CI = 0.66–0.84, P < 0.05). Analyses did not indicate statistically significant results against laboratory‐confirmed influenza (RR = 0.87, CI = 0.74–1.03, P > 0.05). CONCLUSIONS: N95 respirator use was associated with fewer viral infectious episodes for healthcare workers compared with surgical masks. The N95 respirator was most effective in reducing the risk of a viral infection in the hospital setting from the SARS‐CoV 1 and 2 viruses compared to the other viruses included in this investigation. Methodologic quality, risk of biases, and small number of original studies indicate the necessity for further research to be performed, especially in front‐line healthcare delivery settings.

air leakage. Unfortunately, prolonged N95 respirator use is associated with discomfort and headaches, leading to improper doffing and decreased compliance, causing increased infection rates among these non-compliant users. 5, 6 Surgical masks on the other hand are defined as loose-fitting devices that provide a physical barrier between the mouth and nose of the user and the immediate environment. They are designed to reduce microorganism transmission among wearers, prevent gross contamination, and fit more loosely on the user's face. 7 Unlike the N95 respirator these surgical masks cannot prevent inhalation of very small airborne particles because of the lack of a filtration mechanism; however, both have shown protective effects from large droplets and sprays. 8, 9 Each of these mask types are essential in the healthcare setting as measures of PPE and in the community to stop the spread of viral respiratory illnesses. 10 

Current recommendations for airborne protection against SARS and pandemic influenza from the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) are conflicting.

The May 2021 CDC guidelines recommend using respirators in low and high-risk situations, whereas the most current WHO guidelines recommend surgical masks in low-risk situations and respirators in highrisk situations. 11, 12 During the current COVID-19 pandemic, civilians have been purchasing N95 respirators, decreasing the supply and availability to hospitals and healthcare workers, potentially putting frontline workers at increased risk of infection. 13 Previous studies have shown that existing clinical evidence has been inconclusive and inconsistent regarding whether N95 respirators are more effective than surgical masks for preventing viral respiratory infection among healthcare professionals. 9, 14, 15 The number of randomized controlled trials (RCTs) have led to a limited amount of evidence supporting N95 respirator use versus surgical masks. Studies also did not stratify the type of surgical mask based on level of protection when comparing to N95 respirators.

Ideally, clinical decision making should be founded on high levels of evidence to best protect healthcare workers from infection.

During initial presentation to first responders or in front-line settings such as the emergency department, vaccination history and immunity status are usually unknown for patients at risk for communicable illness such as COVID-19; the initial unknown state must be handled with the safety of the healthcare team in mind using PPE with the highest margin of safety. However, later in the course of care when an infectious state has been determined, directed PPE application can be used.

Recent increases in the number of RCTs of N95 respirator and surgical mask use for protection against viral respiratory illnesses have increased the pool of data. A systematic review and meta-analysis from 2020 studied the effectiveness of N95 respirators versus surgical masks against influenza, including related RCTs. 16 This current study of existing literature is aimed to assess the level of evidence provided in these studies and analyze the data assessing N95 respirator use versus surgical mask use for the prevention not only of influenza but also other viral respiratory illness from all original research studies.

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)

guidelines. 17, 18 The primary focus was on the association of N95 respirator and surgical mask effectiveness in reducing viral respiratory disease infection and the level of evidence supporting these data. 

Two reviewers independently screened articles based on title and abstract, then full text ( Figure 1 ). Reviewers extracted data from the included studies and disagreements were resolved by discussion to come to a consensus. All studies that met the inclusion criteria were used and sensitivity analyses were run for each result group to minimize study selection bias. 

Reviewers assessed the risk of bias of the RCTs included in this review, following the Cochrane Risk of Bias tool. 21 This assessment included identification of several types of biases that could affec the quality of the RCT, including but not limited to selection bias, performance bias, detection bias, attrition bias, reporting bias, and an overall consolidation and classification of these biases among 3 levels (high, some, and low risk). Studies with negative methodology regarding these previously mentioned types of biases were determined to be at high risk of overall bias. Studies that did not specifically report these methods were labeled some risk of bias. Those that used strict methodology to account for such biases were noted as low risk of bias. Disagreements among bias classification were resolved by discussion.

All data analyses were performed using the program R version 3.4.3.

Studies that presented comparable data with similar interventions and outcome results were pooled together for joint analysis of the larger sample size. The effect of these studies was conducted using risk ratios (RR) with 95% confidence intervals (CIs) for the dichotomous data. One-factor-at-a-time sensitivity analyses revealed that results 

The details of our literature search and screening process of articles are found in Figure 1 . In total, we included 4 RCTs, 22-15 3 case control studies, [25] [26] [27] and 1 retrospective cohort study. 28 The characteristics of these studies are found in Table 2 

Of the RCTs, all were level I evidence, whereas the case-control studies and retrospective cohort study were level III evidence. Of these included studies, 50% presented level I evidence, and 50% presented level III evidence. However, of the 4 included RCTs, only 1 presented statistically significant results measuring our primary outcomes, and none of the individual case-control or retrospective cohort studies had statistically significant findings regarding mask type effectiveness differences. The non-RCTs did present statistically significant findings regarding the general protective effect of N95 respirators and surgical masking practices versus infection rates.

The summary of results of the Cochrane Risk of Bias tool can be seen in Table 3 . None of the studies reported an assessment of compliance with the protocol regarding surgical mask or respirator use. Blinding of participants and personnel (performance bias) was taken as the main factor for deciding the overall risk of bias of a study. Overall, 1 of the included RCTs was deemed high risk of bias, 1 had some risk, and 2 had low risk.

The Loeb et al. study 22 Abbreviation: RCT, randomized controlled trial.

Results of N95 respirator effectiveness versus surgical masks against influenza-like illness. Abbreviations: LCL, lower confidence limit; POP, population; RR, risk ratio; UCL, upper confidence limit; WGT, weight "some bias" classification owing to the increased likelihood of performance and detection biases. 

This study is not without limitations. The overall study risk of biases poses a limitation to the quality of evidence included in this metaanalysis. Additionally, all the included trials were potentially heterogeneous in their surgical masking type, as they did not disclose the manufacturers. Although mostly consistent, the viruses assessed by each of the trials was not uniform; these viruses may transmit, reproduce, and mutate uniquely. Likely the largest limitation of each of the included studies was the lack of masking compliance assessment. Despite these limitations, an examination of the included articles showed that they each described very similar overall techniques when comparing masking effectiveness in the hospital setting.

This meta-analysis has shown that much of the research studying N95 Healthcare professionals have stated discomfort, most often headaches, associated with N95 respirator use. 5 Because healthcare professionals are often required to wear these respirators for prolonged periods to protect against infection, side effects of use may become a deterrent to compliance. A 2017 study showed an inverse relationship between level of compliance of wearing N95 respirators and risk of clinical respiratory infection. 6 In all studies comparing the effects of N95 respirators, it is difficult to ensure participant compliance throughout the study, because of the discomfort associated with wearing the masks. This decreased compliance associated with N95 respirator use may lead to respirator manipulation and adjustment, as well as frequent removal and reapplication, 29 affecting the study outcomes comparing the respirators versus surgical masks. Although the aerosol particle filtration ability of the N95 respirator is a distinguishing feature between it and the surgical mask in a laboratory setting with ideal compliance, 30 the discomfort associated with wearing these masks in a work environment may inhibit healthcare workers from closely following respirator use protocols.

In vitro studies have shown that surgical mask particulate filtration efficiency for 0.1 micron aerosol particles and bacterial filtration efficiency of 3.0 micron Staphylococcus aureus aerosol particles are consistently >96%, implying the surgical mask's high performance to reduce infection transmission. 30 These laboratory studies have also indicated increased filter performance and simulated-workplace protection factors with fit-tested N95 respirators than surgical masks. 7 High rates of influenza virus recovery from contaminated surgical masks and N95 respirators has also been reported, 31 whereas improper doffing of PPE such as N95 respirators, face shields, and surgical masks have been shown to cause self-contamination with viral respiratory illnesses. 32 These findings highlight the need for understanding the interpretation of data of the included studies for this meta-analysis and detail the possibility of confounding variables, such as non-compliance from strict N95 respirator use protocol.

Although much of the discussion in the literature regards the comparison of surgical masks to N95 masks or other respirators, their intended functions are quite different. The N95 and powered air purifying respirators (PAPR) are designed to protect the wearer from the environment by reducing particle inhalation, but surgical masks are designed to reduce spread of infection from the wearer and prevent gross contamination during surgery. 33 There is a risk of type II error in this small group of included RCTs because of the limited size of the populations being studied. There is also a risk of publication bias that we cannot determine owing to the limited number of related RCTs. Additionally; the number of RCTs and other studies that fulfilled the inclusion criteria for the analysis was small. Finally, these studies were performed before vaccine development for COVID-19, but with other vaccines available (eg., influenza). 45 Vaccine administration for a given virus does not guarantee immunity and viral mutation can also limit vaccine effectiveness, which necessitates the ongoing use of optimal PPE especially for front-line physicians and healthcare team. The effect of vaccines on PPE effectiveness warrants further investigation and is beyond the scope of this analysis.

The authors recommend that further RCTs that compare surgical masks to N95 respirators (1) assess compliance with surgical mask and respirator use; (2) analyze viral illness in each group with PCR and antibody-based assays before, during, and after the study period for all participating healthcare workers; (3) study a single viral pathogen; (4) focus the study location on a single treatment setting (eg, emergency medicine, inpatient hospital, or perioperative settings). These criteria will better control confounding variables and determine the relationship between N95 respirators and surgical masks to reduce viral infection in focused treatment settings.

Results comparing N95 respirators and surgical masks for influenzalike-illness (included clinical diagnoses) ( Figure 2 ) and laboratoryconfirmed influenza infection (Figure 7) In settings with high institutional and regional COVID-19 infection 

Therapeutic Options for COVID-19 Patients

Physical interventions to interrupt or reduce the spread of respiratory viruses

Interim guidance for managing healthcare personnel with SARS-COV-2 infection or exposure to SARS-COV-2. Centers for Disease Control and Prevention

Performance of N95 respirators: filtration efficiency for airborne microbial and inert particles

Headaches and the N95 face-mask amongst healthcare providers

Herd protection effect of N95 respirators in healthcare workers

Comparison of performance of three different types of respiratory protection devices

Protecting healthcare staff from severe acute respiratory syndrome: filtration capacity of multiple surgical masks

Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis

To mask or not to mask: modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic

Prevention strategies for seasonal influenza in healthcare settings

Identification and Management of Health Worker in the Context of COVID-19

Assessment of proficiency of N95 mask donning among the general public in Singapore

Effectiveness of masks and respirators against respiratory infections in healthcare workers: a systematic review and meta-analysis

N95 respirators vs medical masks for preventing influenza among health care personnel: a randomized clinical trial

Effectiveness of N95 respirators versus surgical masks against influenza: a systematic review and meta-analysis

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Centre for Evidence-Based Medicine (CEBM)

Cochrane Handbook for Systematic Reviews of Interventions Version 6.2. Cochrane Databases. www.training.cochrane.org/handbook

Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial

A cluster randomized clinical trial comparing fit-tested and non-fit-tested N95 respirators to medical masks to prevent respiratory virus infection in health care workers. Influen Other Respir Viruses

A randomized clinical trial of three options for N95 respirators and medical masks in health workers

Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS)

Survey of COVID-19 disease among orthopaedic surgeons in Wuhan, People's Republic of China

Factors associated with the transmission of pandemic (H1N1) 2009 among hospital healthcare workers in Beijing, China. Influenza Other Respir Viruses

SARS among critical care nurses

Face masks to prevent transmission of influenza virus: a systematic review

Surgical mask filter and fit performance

Assessment of influenza virus exposure and recovery from contaminated surgical masks and N95 respirators

Self-contamination during doffing of personal protective equipment by healthcare workers to prevent Ebola transmission

Grinshpun SA. Do N95 respirators provide 95% protection level against airborne viruses, and how adequate are surgical masks?

Use of powered air-purifying respirator (PAPR) by healthcare workers for preventing highly infectious viral diseases-a systematic review of evidence

Use of powered air-purifying respirator(PAPR) as part of protective equipment against SARS-CoV-2-a narrative review and critical appraisal of evidence

Protecting healthcare workers from pandemic influenza: n95 or surgical masks?

Your guide to masks. Centers for Disease Control and Prevention

Low-cost measurement of face mask efficacy for filtering expelled droplets during speech

A schlieren optical study of the human cough with and without wearing masks for aerosol infection control

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2). Science

Differences and similarities between Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV) and SARS-CoV-2. Would a rose by another name smell as sweet?

Review of aerosol transmission of influenza A virus

A systematic review of possible airborne transmission of the COVID-19 virus (SARS-CoV-2) in the indoor air environment

Particle sizes of infectious aerosols: implications for infection control

SARS-CoV-2 vaccines: status report

Asymptomatic and human-to-human transmission of SARS-CoV-2 in a 2-Family Cluster

Public health-Seattle & King County; CDC COVID-19 investigation team. asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility

Assessment of the SARS-CoV-2 basic reproduction number, R0, based on the early phase of COVID-19 outbreak in Italy

N95 respirator and surgical mask effectiveness against respiratory viral illnesses in the healthcare setting: A systematic review and meta-analysis

The authors received no source of external funding for this review.

The authors report no conflicts of interest pertaining to this work. For full listing of conflicts of interest, please see American Academy of Orthopaedic Surgeons Conflicts of Interest disclosures.

All authors contributed to data analysis, drafting or revision of the arti-