EditorialsMarch 2021The Role of Masks in Mitigating the SARS-CoV-2 Pandemic: Another Piece of the PuzzleFREEChristine Laine, MD, MPH, Steven N. Goodman, MD, MHS, PhD, and Eliseo Guallar, MD, MPH, DrPHChristine Laine, MD, MPHEditor in Chief, Annals of Internal Medicine Search for more papers by this author, Steven N. Goodman, MD, MHS, PhDStanford University School of Medicine Stanford, CaliforniaSearch for more papers by this author, and Eliseo Guallar, MD, MPH, DrPHDeputy Editor, Statistics, Annals of Internal Medicine Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-7448 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Is transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reduced if most people in a community wear masks? If most people do not wear masks but some do, are the mask wearers protected? These are among the most critical public health questions of this moment, but they are very different questions. In this context, Annals publishes Bundgaard and colleagues' much-anticipated report of DANMASK-19 (Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection), the first randomized controlled trial of a mask recommendation to mitigate SARS-CoV-2 infection (1). We must first emphasize that this trial does not address the first question about transmission in communities where most people wear masks and does not disprove the effectiveness of widespread mask wearing. We explain how this trial adds to what we know about masks in the community and risk for SARS-CoV-2 infection.Masks may mitigate SARS-CoV-2 transmission by preventing spread from infected people to others (source control), by protecting wearers (protective effect), or both. Source control is believed to be the predominant mechanism for reducing SARS-CoV-2 transmission because transmission can occur before symptoms develop and many infections are asymptomatic. The DANMASK-19 trial was designed to examine only the masks' protective effect, not source control. The investigators took advantage of a unique situation in Denmark during the spring of 2020. Social distancing recommendations were in effect, but masks were not recommended, they were rarely worn outside of hospitals, and the infection rate was modest. The study end point was infection in the mask wearer rather than infection in their contacts or the overall community infection rate. Although some believe that randomized trials of masks are infeasible (2), this trial was carefully conducted in a real-world setting. The researchers recruited 6024 adults who spent at least 3 hours outside their homes per day, had occupations that did not require masks, and did not have a previous known diagnosis of SARS-CoV-2 infection. Participants were randomly assigned to follow social distancing measures with or without an additional recommendation to wear a mask when outside the home among other people, and they also received a supply of surgical masks. They completed weekly surveys as well as antibody tests with polymerase chain reaction testing at 1 month and if coronavirus disease 2019 (COVID-19) symptoms developed. Although false positives occur with antibody tests, the end point of the trial was seroconversion after a negative test result at baseline. With this design, participants with cross-reacting serum components that produce false positives are removed from the analysis, thus increasing the likelihood that seroconversions are true-positive results. The investigators excluded 68 participants with positive antibody test results at baseline, 134 with errors in the distribution of the study kits, and 960 who did not complete the trial. After 1 month of follow-up, 1.8% (42 of 2392) of participants in the mask group and 2.1% (53 of 2470) in the control group developed infection (risk difference, −0.3 percentage point [95% CI, −1.2 to 0.4 percentage point] [P = 0.38]; odds ratio, 0.82 [CI, 0.54 to 1.23] [P = 0.33]). Although these results showed that mask recommendations did not decrease personal infection rates by the target of 50% that the trial was designed to detect, the estimates were imprecise and statistically compatible with an effect ranging from a 46% decrease to a 23% increase in infection. In other words, the evidence excludes a large personal protective effect, weakly supports lesser degrees of protection, and cannot statistically exclude no effect.Two aspects are important to note. First, the study examined the effect of recommending mask use, not the effect of actually wearing them. Adherence to public health recommendations is always imperfect, as it was in this study, and can differ dramatically in communities with different attitudes toward such recommendations. Second, the effect of a mask recommendation also depends on many other factors, including the prevalence of the virus, social distancing behaviors, and the frequency and characteristics of gatherings. Mask wearing is just one of several interacting strategies to reduce viral transmission, with each reinforcing the others.If the DANMASK-19 trial was not designed to answer a key public health question regarding widespread mask wearing as source control and did not provide a precise estimate of the personal protective effect of masks, why did Annals publish it?Like most critical public health issues, questions about the role of masks in mitigating SARS-CoV-2 infection are not going to be answered by a single study. This trial provides an important piece of randomized evidence as we puzzle over a contentious public health issue: the degree of personal protection that a mask wearer can expect in a setting where public health social distancing measures are in effect but other people are not wearing masks. The U.S. Centers for Disease Control and Prevention recently updated its guidance to acknowledge that masks, when worn by all, may reduce transmission via both source control and personal protection (3). The current trial shows that any contribution of masks to risk reduction in the community through personal protection is likely to be small. Mask wearing by a minority of persons—even with high-quality surgical masks like the ones provided to trial participants—does not make the wearers invulnerable to infection.The DANMASK-19 findings reinforce the importance of social distancing and hygiene measures and suggest that masks likely need to be worn by most if not all people to reduce community infection rates, which in turn will protect individuals. In the context of observational studies that show lower SARS-CoV-2 transmission in communities with widespread mask wearing (4–7) and the absence of serious adverse health effects of wearing masks (8), the results of this trial should motivate widespread mask wearing to protect our communities and thereby ourselves while we await more definitive evidence during this pandemic.With fierce resistance to mask recommendations by leaders and the public in some locales, is it irresponsible for Annals to publish these results, which could easily be misused by those opposed to mask recommendations?We think not. More irresponsible would be to not publish the results of carefully designed research because the findings were not as favorable or definitive as some may have hoped. We need to gather many pieces of evidence to solve the puzzle of how to control the SARS-CoV-2 pandemic. For this reason, we thought it important to publish the findings and carefully highlight the questions that the trial does and does not answer.All who worry about the COVID-19 pandemic should carefully consider these findings for what they show and refrain from viewing them as evidence that widespread mask wearing is ineffective. While we await additional evidence about the effectiveness of masks as source control of SARS-CoV-2 transmission, we are going to do our part to protect everyone by masking up and hope that those around us do the same.