Background: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators. Objective: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care. Design: Multicenter, randomized, noninferiority trial. (ClinicalTrials. gov: NCT04296643). Setting: 29 health care facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022. Participants: 1009 health care workers who provided direct care to patients with suspected or confirmed COVID-19. Intervention: Use of medical masks versus fit-tested N95 respirators for 10 weeks, plus universal masking, which was the policy implemented at each site. Measurements: The primary outcome was confirmed COVID-19 on reverse transcriptase polymerase chain reaction (RT-PCR) test. Results: In the intention-to-treat analysis, RT-PCR-confirmed COVID-19 occurred in 52 of 497 (10.46%) participants in the medical mask group versus 47 of 507 (9.27%) in the N95 respirator group (hazard ratio [HR], 1.14 [95% CI, 0.77 to 1.69]). An unplanned subgroup analysis by country found that in the medical mask group versus the N95 respirator group RT-PCR-confirmed COVID-19 occurred in 8 of 131 (6.11%) versus 3 of 135 (2.22%) in Canada (HR, 2.83 [CI, 0.75 to 10.72]), 6 of 17 (35.29%) versus 4 of 17 (23.53%) in Israel (HR, 1.54 [CI, 0.43 to 5.49]), 3 of 92 (3.26%) versus 2 of 94 (2.13%) in Pakistan (HR, 1.50 [CI, 0.25 to 8.98]), and 35 of 257 (13.62%) versus 38 of 261 (14.56%) in Egypt (HR, 0.95 [CI, 0.60 to 1.50]). There were 47 (10.8%) adverse events related to the intervention reported in the medical mask group and 59 (13.6%) in the N95 respirator group. Limitation: Potential acquisition of SARS-CoV-2 through household and community exposure, heterogeneity between countries, uncertainty in the estimates of effect, differences in self-reported adherence, differences in baseline antibodies, and between-country differences in circulating variants and vaccination. Conclusion: Among health care workers who provided routine care to patients with COVID-19, the overall estimates rule out a doubling in hazard of RT-PCR-confirmed COVID-19 for medical masks when compared with HRs of RT-PCR-confirmed COVID-19 for N95 respirators. The subgroup results varied by country, and the overall estimates may not be applicable to individual countries because of treatment effect heterogeneity.
