By Jake Scott, MD
Clinical Assistant Professor, Infectious Diseases and Geographic Medicine, Stanford University School of Medicine; Antimicrobial Stewardship Program Medical Director, Stanford Health Care Tri-Valley
SYNOPSIS: A multicenter, randomized, controlled study found that medical masks were noninferior to N95 respirators in their relative protection against COVID-19 among healthcare workers when worn while providing routine care to patients with suspected or confirmed COVID-19.
SOURCE: Loeb M, Bartholomew A, Hashmi M, et al. Medical masks versus N95 respirators for preventing COVID-19 among health care workers: A randomized trial. Ann Intern Med 2022;175:1629-1638.
Loeb and colleagues conducted a randomized controlled trial to examine how the effectiveness of medical masks compares to N95 respirators in their protection against SARS-CoV-2 infection when worn by healthcare workers (HCWs) providing routine care to patients with suspected or confirmed COVID-19. The study focused on whether medical masks were noninferior to N95 respirators in their relative protection of HCWs performing clinical work in various settings. Participants were observed over a 10-week period in 29 healthcare facilities: 17 acute care hospitals in Canada, four acute care hospitals in Pakistan, two long-term care facilities in Israel, and six acute care hospitals in Egypt. The study included emergency departments and inpatient adult and pediatric medical units but did not include intensive care units. Enrollment occurred at different periods among sites between May 2020 and March 2022. Participants were excluded if they had not had a valid N95 fit test, had one or more high-risk comorbidities, had a previous diagnosis of COVID-19, or if they had received one or more doses of a “highly effective” COVID-19 vaccine. Those who had received one or more doses of a COVID-19 vaccine with at least 50% efficacy for the circulating SARS-CoV-2 strain were followed for two weeks after their first vaccine dose and then were censored. Investigators and laboratory personnel were blinded to the group assignment, but staff and participants were not.
All facilities had a preexisting policy of requiring the use of medical masks when providing routine care to COVID-19 patients. HCWs in the medical mask group were given the option of using an N95 respirator at any time based on a point-of-care assessment. In addition, all participants were required to universally mask for all activities and to wear N95 respirators during aerosol-generating procedures. The primary outcome was time to reverse transcriptase polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection and the noninferiority margin used was a hazard ratio (HR) of 2. Adherence to the assigned device was measured using weekly self-reporting for all participants as well as sporadic audits, which were conducted at some of the facilities but only for a fraction of the participants. Participants were asked to keep track of symptoms and whether they potentially were exposed to household and community members with a respiratory illness.
Among the 1,009 HCWs enrolled in the study, 500 were randomly assigned to wear medical masks and 509 to wear N95 respirators. Two hundred sixty-eight participants were from Canada, 34 were from Israel, 187 were from Pakistan, and 520 were from Egypt. The median age was 35 years. The majority of participants were female nurses who worked in acute care settings. While baseline characteristics were similar between the two groups, the baseline seropositivity among participants varied considerably by country. Prior to enrollment, very few of the HCWs in Canada were seropositive (2.3% in the medical mask group and 1.6% in the N95 group), yet the majority of those in Egypt were seropositive (81.6% and 80.5%, respectively). There was balance overall, however, between the groups; 37.5% of participants in the medical mask group and 37.2% of those in the N95 group were seronegative at baseline.
In the intention-to-treat analysis, the primary outcome of COVID-19 occurred in 52 of 497 (10.46%) in the medical mask group compared to 47 of 507 (9.27%) in the N95 respirator group (HR, 1.14; 95% confidence interval [CI], 0.77 to 1.69). Heterogeneity in treatment effect was found between countries in an unplanned subgroup analysis. COVID-19 occurred in eight of 131 (6.11%) participants in the medical mask group vs. three of 135 (2.22%) in the N95 respirator group in Canada (HR, 2.83; CI, 0.75 to 10.72), six of 17 (35.29%) vs. four of 17 (23.53%) in Israel (HR, 1.54; CI, 0.43 to 5.49), three of 92 (3.26%) vs. two of 94 (2.13%) in Pakistan (HR, 1.50; CI, 0.25 to 8.98), and 35 of 257 (13.62%) vs. 38 of 261 (14.56%) in Egypt (HR, 0.95; CI, 0.60 to 1.50). Omicron was only in circulation during the enrollment period in Egypt (Dec. 19, 2021, to March 29, 2022); enrollment in all other countries concluded prior to the emergence of Omicron. In post hoc subgroup analyses, there was not a significant difference in treatment effect between those who reported no household or community exposure to a respiratory illness (HR, 1.06; CI, 0.53 to 2.11) compared to those who reported one or more exposure (HR, 1.08; CI, 0.66 to 1.78); nor was there a significant difference based on serostatus.
There were more adverse events attributed to the use of N95 respirators compared to medical masks – 59 (13.6%) vs. 47 (10.8%), respectively. These included discomfort (9.7% in the N95 group vs. 4.6% in the medical mask group), skin irritation (5.8% vs. 5.1%), and headaches (6.7% vs. 4.6%). Self-reported adherence to wearing the assigned mask or respirator varied between groups — 91.2% of those in the medical mask group self-reported “always” being adherent, compared to 80.7% in the N95 respirator group. Adherence based on random audits differed less — 98.3% in the medical mask group vs. 96.6% in the N95 respirator group. The amount of known occupational and community exposures to individuals with COVID-19 were reported to be similar between groups.
COMMENTARY
The Centers for Disease Control and Prevention (CDC) has recommended that HCWs wear N95 respirators during the routine care of patients with suspected or confirmed SARS-CoV-2 infection (e.g., when entering the room of a patient), while the World Health Organization (WHO) has recommended either an N95 respirator or a medical mask in these scenarios. High-quality, real-world data on the relative protection conferred by these different devices had not existed when these recommendations were made, and occupational guidance for HCWs providing non-aerosol generating patient care has varied throughout the world.
This pragmatic study by Loeb and colleagues is the first randomized trial to have compared N95 respirators to medical masks in HCWs and any difference in risk of COVID-19. The focus of the study was relatively narrow. It specifically assessed whether HCWs who were required to wear medical masks while providing routine care to patients with suspected or confirmed COVID-19 had a doubling in the hazard of acquiring COVID-19 as compared to HCWs required to wear N95 respirators instead. Since fit-tested N95 respirators are more tightly worn and filter better than medical masks, they are generally considered to be mechanistically superior and, therefore, more effective than medical masks at reducing the risk of acquiring SARS-CoV-2 infection when worn properly. Medical masks, however, are cheaper, generally more comfortable, and more widely available; for this reason, a noninferiority study design was appropriate.
The cumulative risk of acquiring SARS-CoV-2 infection over a period of weeks may depend on variables other than the quality of mask or respirator specifically worn while providing routine care to patients with COVID-19, which include variability in adherence, differences in exposures inside and outside of the healthcare setting, the transmissibility and levels of variants in circulation, and the immune status of the individual. Adherence was self-reported as being lower in the N95 respirator group, likely related to differences in comfort, which could have contributed to less effectiveness. However, the study allowed participants in the medical mask group to choose to wear an N95 respirator at any time, which also could have influenced the primary outcome if participants assigned to wear medical masks actually wore N95 respirators during exposures instead; it is not clear from the paper how often this was done.
When the HR estimates of this study were pooled, a wide range in relative protection against COVID-19 was found, from a 23% reduction in the hazard to a 69% increase in the hazard when assigned to wear a medical mask. There was close to a null effect of medical masks compared to N95 respirators in the Egypt group (HR, 0.95; CI, 0.60 to 1.50), where the majority of the participants (51.5%) were enrolled. This particular subgroup result may be the most relevant to the current pandemic conditions, since the Egypt group had high levels of seroprevalence and since Omicron was in circulation during enrollment.
In summary, this study demonstrated that there was not a large statistical difference in the overall protective effect of requiring HCWs to wear an N95 respirator while providing routine care to COVID-19 patients. Whether there is a smaller statistical difference in protective effect in these particular clinical scenarios remains uncertain.
REFERENCES
- Centers for Disease Control and Prevention. Interim infection prevention and control recommendations for healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic. Updated Sept. 23, 2022. https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html#print
- World Health Organization. WHO recommendations on mask use by health workers, in light of the Omicron variant of concern: WHO interim guidelines, 22 December 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-IPC_Masks-Health_Workers-Omicron_variant-2021.1
