Of Masks and Methods
Authors: Thomas R. Frieden, Shama Cash-Goldwasser
Journal: Annals of Internal Medicine (2020)

EditorialsMarch 2021Of Masks and MethodsFREEThomas R. Frieden, MD, MPH and Shama Cash-Goldwasser, MD, MPHThomas R. Frieden, MD, MPHResolve to Save Lives, an initiative of Vital Strategies New York, New York and Shama Cash-Goldwasser, MD, MPHResolve to Save Lives, an initiative of Vital Strategies New York, New YorkAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-7499 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The coronavirus disease 2019 (COVID-19) pandemic is the most disruptive health event in a century. In less than a year, it will have killed at least 1.5 million people and cost the global economy more than $20 trillion. Although progress toward a vaccine has been fast, core public health interventions remain the mainstay of control and will continue to be essential after vaccines become available. Strategic closure of risky indoor environments, such as bars, restaurants, and choirs, reduces spread. Testing, rapid isolation, contact tracing, and quarantine prevent cases and clusters from spreading. Use of face masks has emerged as a powerful tool to reduce the health and economic harms of the pandemic (1).The fact that viral loads are highest just before and early in the course of illness provides the theoretical basis for widespread community mask use as source control, and the evidence that wearing of masks prevents spread to others is compelling (1). Observational studies have shown that mask use in the community is associated with a significantly lower risk for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (2). Although evidence suggests that masks protect wearers from infection (3) and there is mechanistic evidence that masks not only block release of respiratory droplets but also reduce wearer exposure (4), whether masks protect wearers from infection has been the subject of controversy. The protection a mask offers the wearer depends in part on the duration, location (for example, home vs. public), and intensity (for example, health care vs. community) of exposure; type of mask; and consistency of use. In addition, the methods used to evaluate whether masks protect wearers affect study results.The DANMASK-19 (Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection) randomized controlled trial (5) was done during spring 2020 in Denmark, when use of masks in the community was not recommended by the Danish Health Authority but other public health and social measures to limit transmission of SARS-CoV-2 were in effect. Intervention group participants received 50 disposable surgical face masks and instructions to wear a mask while outside home for 1 month. The primary outcome was infection with SARS-CoV-2, defined as 1) positive results of lateral flow testing for anti–SARS-CoV-2 IgM or IgG antibodies at 1 month, 2) positive results of polymerase chain reaction testing for SARS-CoV-2 at 1 month and symptoms compatible with COVID-19, or 3) diagnosis of COVID-19 by a health care practitioner. Participants with positive baseline results on an antibody test were excluded from analyses.The primary outcome according to the protocol occurred in 1.8% of participants (42 of 2392) in the intervention group and 2.1% (53 of 2470) in the control group. In the intention-to-treat analysis, the intervention group had 0.3 percentage point (95% CI, −0.4 to 1.2 percentage point) fewer SARS-CoV-2 infections than the control group. Across all analyses (intention-to-treat, per protocol, and with multiple imputation for missing data), odds ratios were approximately 0.8, consistent with a 20% reduction in incident SARS-CoV-2 infection if masks are recommended. The sample size was insufficient to determine the statistical significance of a 20% reduction.The specifics of the study setting limit not only its statistical power but also the generalizability of findings. The study was done in a setting with relatively low transmission: During the first week of May, the daily incidence of new confirmed COVID-19 cases in Denmark was roughly one third of that in the United Kingdom and one quarter of that in the United States (6). Furthermore, the study was underpowered for subgroup analyses by occupation, time out of home (although more time out of home was associated with a greater trend toward protection, as shown in Supplement Figure 2 [5]), and other factors. Thus, the potential benefit of mask wearing in particular circumstances or settings could not be assessed.Perhaps the most important limitation of this study was the use of antibody tests to diagnose COVID-19. Of COVID-19 diagnoses in this study, 84% (80 of 95) were made by antibody testing. The accuracy of anti–SARS-CoV-2 antibody tests varies widely (7). Although an internal validation study of the assay used in DANMASK-19 estimated a specificity of 99.5%, the manufacturer reported (www.accessdata.fda.gov/cdrh_docs/presentations/maf/maf3285-a001.pdf) a specificity of 97.5% (CI, 91.3% to 99.3). If test specificity was 98.5% and the 1.5% (1 − specificity) chance of a false-positive result was due to random laboratory variation, Bayes' law implies that all of the antibody-positive results in both intervention and control groups could have been false positives. False positivity due to cross-reactive antibodies would have resulted in baseline exclusion, so the actual rate of false positives in participants after 1 month may be low. Nevertheless, given the very low (at most 2%) prevalence of infection, many of the follow-up positives may have been falsely positive and would be randomly distributed between intervention and control groups. This would bias the study's findings toward the null.In addition, a mask recommendation or self-report of use does not equate with correct mask wearing; among persons who wear masks during high-risk exposures, risk for infection may be reduced significantly (3). In DANMASK-19, only 46% of those in the intervention group reported adherence to the intervention. Women may be more likely to adhere to public health recommendations than men (8). Among female participants, the decreased odds of infection with SARS-CoV-2 among those in the intervention group compared with those in the control group approached statistical significance (odds ratio, 0.65 [CI, 0.38 to 1.12]); this trend could also have been biased toward the null by similar numbers of false positives in both groups.Community mask use can substantially reduce risk for SARS-CoV-2 transmission, especially when enough people use them and when mask use is combined with other effective public health and social measures. Multiple observational studies have documented an association between mask mandates and reduced COVID-19 incidence (9). Although randomized controlled trials are often presumed to provide the highest-quality data, observational studies may in some settings be more accurate and can overcome some limitations of other data sources (10).Although no single strategy can control the pandemic, widespread masking in the community can mitigate spread as part of a comprehensive approach. Masks have been shown to protect others and, despite the reported results of this study, probably protect the wearer. Maximum benefit of masking is likely to result from the combination of source control and wearer protection (1). If everyone wears a mask when near others, everyone is safer.References1. Centers for Disease Control and Prevention. Scientific brief: community use of cloth masks to control the spread of SARS-CoV-2. 10 November 2020. Accessed at www.cdc.gov/coronavirus/2019-ncov/more/masking-science-sars-cov2.html on 14 November 2020. Google Scholar2. Chu DK, Akl EA, Duda S, et al; COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020;395:1973-87. [PMID: 32497510] doi:10.1016/S0140-6736(20)31142-9 Google Scholar3. Doung-Ngern P, Suphanchaimat R, Panjangampatthana A, et al. Case-control study of use of personal protective measures and risk for SARS-CoV 2 infection, Thailand. Emerg Infect Dis. 2020;26:2607-16. [PMID:32931726] doi:10.3201/eid2611.203003 Google Scholar4. Ueki H, Furusawa Y, Iwatsuki-Horimoto K, et al. Effectiveness of face masks in preventing airborne transmission of SARS-CoV-2. mSphere. 2020;5. [PMID: 33087517] doi:10.1128/mSphere.00637-20 Google Scholar5. Bundgaard H, Bundgaard JS, Raaschou-Pedersen DET, et al. Effectiveness of adding a mask recommendation to other public health measures to prevent SARS-CoV-2 infection in Danish mask wearers. A randomized controlled trial. Ann Intern Med. 2021;174:335-43. doi:10.7326/M20-6817 Google Scholar6. Ritchie H, Ortiz-Ospina E, Beltekian D, et al. Coronavirus pandemic (COVID-19). 14 November 2020. Accessed at https://ourworldindata.org/coronavirus on 14 November 2020. Google Scholar7. Deeks JJ, Dinnes J, Takwoingi Y, et al; Cochrane COVID-19 Diagnostic Test Accuracy Group. Antibody tests for identification of current and past infection with SARS-CoV-2. Cochrane Database Syst Rev. 2020;6:CD013652. [PMID: 32584464] doi:10.1002/14651858.CD013652 Google Scholar8. Galasso V, Pons V, Profeta P, et al. Gender differences in COVID-19 attitudes and behavior: panel evidence from eight countries. Proc Natl Acad Sci U S A. 2020;117:27285-91. [PMID: 33060298] doi:10.1073/pnas.2012520117 Google Scholar9. Cash-Goldwasser S, Kardooni S, Kachur SP, et al. Weekly COVID-19 science review October 3–9. Resolve to Save Lives. 13 October 2020. Accessed at https://preventepidemics.org/covid19/science/weekly-science-review/october-3-9 on 14 November 2020. Google Scholar10. Frieden TR. Evidence for health decision making—beyond randomized, controlled trials. N Engl J Med. 2017;377:465-75. [PMID: 28767357] doi:10.1056/NEJMra1614394 Google Scholar Comments0 CommentsSign In to Submit A Comment Edward Siguel, MD, PhDSelf employed in biomedical research, MD, USA.23 November 2020 Science clearly predicts that facemasks reduce fluids expelled and prevent outside fluids from touching face. There is misplaced focus on clinical trials and data analysis, the focus should be on the biophysics of the process (virus transmission). We know about fluid transmission through air and clothing. We learn as children not to spit on other people's faces, avoid being spit on, and protect with a cloth or paper. Simple fluid mechanics. When I taught statistical analysis, thinking, sample size, statistical significance, and "p" values, to college students and physicians, I reminded them of a thought experiment: how many people do we need to throw out of a 10th story window of a hotel, to fall upon a concrete sidewalk, to be reasonably certain that people will break more than 1 bone? Assuming we get "volunteers", 3 are enough. Physics predicts broken bones. We can figure out if facemasks are protective with thought experiment. Have a friend vomit in front of you, or throw a glass of something you do not like (urine is fairly innocuous). Now, ask yourself this theoretical question: how much fluid will get into your face and mouth if you do not have a facemask, and how much will get there if you wear a good facemask? Do you need a PhD in fluid mechanics to answer this question? 10,000 volunteers? What would you prefer when someone coughs or vomits on your face, a facemask or nothing? Incidentally, if you answer nothing, you may want to volunteer to raise money at scientific fairs. Let children and others pay a small fee to throw stuff at your face. This thought experiment tells us that a facemask in front of the face protects us from getting stuff on our face and mouth, liquids, particles, etc. If the facemask has small holes, and is appropriate, it will prevent viral particles from hands or air from entering our face, mouth, nose. How much of a reduction depends on the facemask (obvious). Further, if the facemask is not tight (a common error among users), the air will go around the gaps, following the path of least resistance. I noticed the Earth is flat, does not move, the Sun evolves around the Earth. Do I believe my observations or Newton? Observations can be flawed. We must stop nonsense about facemasks. The studies we need should evaluate the best materials to make facemasks, when to replace them, etc. Not IF to use facemasks, but when, how. Abigail Zuger MDself employed20 November 2020 Adherence Dr. Frieden, I think you are incorrect when you say that "In DANMASK-19, only 46% of those in the intervention group reported adherence to the intervention." In fact, the study reports that "46% of participants wore the mask as recommended [and] 47% predominantly as recommended." In other words, more than 90% were masked most of the time, which is surely consistent with most real world mask wearing. Anthony D ManciniPace University23 November 2020 The Message of the DANMASK-19 Study: Response to Frieden and Cash-Goldwasser The DANMASK-19 study (Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection) is an ambitious rigorous study of mask wearing. Among people with low levels of native mask wearing, a very large sample (N = 6000) was randomly assigned to wear or not to wear a mask, followed for a month, and reliably tested. These unusual methodological strengths should be carefully weighed against the critiques of Frieden and Cash-Goldwasser (FCG), which rest on misleading claims. In fact, this study has something important to tell us, and we would be foolish to ignore it. Generality is Always Constrained FCG contend that the results only apply to low transmission environments. This is not a critique so much as a feature of the study. Every study has constraints on generality. For example, the study is silent on whether masks prevent infected people from infecting others. Knowing whether masks protect the wearer against respiratory disease in environments with low rates of transmission is important information. Specificity of the SARS-CoV-2 Test Is Unlikely to Explain the Null Findings Another critique is that the SARS-CoV-2 antibody tests may produce false positives at a rate exceeding population-level infection. There are two important reasons to discount this possibility. First, false positives would necessarily be coupled with real positives. That is, lower specificity would only inflate positive cases. Unless actual infections are zero, false positives contribute noise, not vitiate the group comparison entirely. Second, FCG mischaracterize the specificity of the SARs-CoV-2 antibody test. The estimate they cite of 97.5% is based on a sample far too small to reliably estimate specificity (80 blood samples). It is also contrary to a larger study done by the DANMASK-19 authors involving a far larger sample (806 samples) and 99.5% specificity (1). Conclusion Although the DANMASK study failed to find protective effects of masks, the effect may have been too small to reliably detect. If so, masks offer a small protective benefit (around 20%), indicating 4 of 5 mask wearers receive no benefit. Even small effects suggest that low-intensity interventions such as masks are advisable. Nevertheless, we must be clear-eyed. This study has implications for how we deploy masks and plan for future pandemics. Science demands we listen. Iversen K, Bundgaard H, Hasselbalch RB, Kristensen JH, Nielsen PB, Pries-Heje M, et al. Risk of COVID-19 in health-care workers in Denmark: an observational cohort study. The Lancet Infectious Diseases. 2020. Author, Article, and Disclosure InformationAffiliations: Resolve to Save Lives, an initiative of Vital Strategies New York, New YorkDisclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7499.Corresponding Author: Thomas R. Frieden, MD, MPH, President and CEO, Resolve to Save Lives, 100 Broadway, 4th Floor, New York, NY 10005; e-mail, [email protected]org.Current Author Addresses: Drs. Frieden and Cash-Goldwasser: Resolve to Save Lives, 100 Broadway, 4th Floor, New York, NY 10005.This article was published at Annals.org on 18 November 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers Henning Bundgaard , Johan Skov Bundgaard , Daniel Emil Tadeusz Raaschou-Pedersen , Christian von Buchwald , Tobias Todsen , Jakob Boesgaard Norsk , Mia M. Pries-Heje , Christoffer Rasmus Vissing , Pernille B. Nielsen , Ulrik C. Winsløw , Kamille Fogh , Rasmus Hasselbalch , Jonas H. Kristensen , Anna Ringgaard , Mikkel Porsborg Andersen , Nicole Bakkegård Goecke , Ramona Trebbien , Kerstin Skovgaard , Thomas Benfield , Henrik Ullum , Christian Torp-Pedersen , and Kasper Iversen Metrics Cited byEvaluation of different types of face masks to limit the spread of SARS-CoV-2: a modeling studyAdapt or die: how the pandemic made the shift from EBM to EBM+ more urgentCDC mask recommendations and guideline development: Missing piecesOfeleein i mi Vlaptin—Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 PandemicMiasmas, mental models and preventive public health: some philosophical reflections on science in the COVID-19 pandemicUsing a cultural and social identity lens to understand pandemic responses in the US and IndiaCOVID-19 false dichotomies and a comprehensive review of the evidence regarding public health, COVID-19 symptomatology, SARS-CoV-2 transmission, mask wearing, and reinfectionCOVID-19: underpowered randomised trials, or no randomised trials?Social Distancing, Mask Use, and Transmission of Severe Acute Respiratory Syndrome Coronavirus 2, Brazil, April–June 2020The road from evidence to policies and the erosion of the standards of democratic scrutiny in the COVID-19 pandemicRapid evidence review to inform safe return to campus in the context of coronavirus disease 2019 (COVID-19) March 2021Volume 174, Issue 3Page: 421-422KeywordsAntibodiesCOVID-19Information storage and retrievalIntent to treat analysisObservational studiesOdds ratioPrevention, policy, and public healthSpecificityUpper respiratory tract infectionsVaccines ePublished: 18 November 2020 Issue Published: March 2021 Copyright & PermissionsCopyright © 2020 by American College of Physicians. 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