The Role of Masks in Mitigating the SARS-CoV-2 Pandemic: Another Piece of the Puzzle
Authors: Christine Laine, Steven N. Goodman, Eliseo Guallar
Journal: Annals of Internal Medicine (2020)

Editorials18 November 2020The 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.References1. 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 Scholar2. Tufekci Z. On masks and clinical trials, Rand Paul's tweeting is just plain wrong. The New York Times. 6 November 2020. Accessed at www.nytimes.com/2020/11/06/opinion/sunday/coronavirus-masks.html on 8 November 2020. Google Scholar3. Centers for Disease Control and Prevention. Scientific Brief: Community Use of Cloth Masks to Control the Spread of SARS-CoV-2. Updated 10 November 2020. Accessed at www.cdc.gov/coronavirus/2019-ncov/more/masking-science-sars-cov2.html on 11 November 2020. Google Scholar4. 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 Scholar5. Chou R, Dana T, Jungbauer R, et al. Masks for prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings. A living rapid review. Ann Intern Med. 2020;173:542-55. [PMID: 32579379] doi:10.7326/M20-3213 Google Scholar6. Qaseem A, Etxeandia-Ikobaltzeta I, Yost J, et al. Use of N95, surgical, and cloth masks to prevent COVID-19 in health care and community settings: living practice points from the American College of Physicians (version 1). Ann Intern Med. 2020;173:642-9. [PMID: 32551813] doi:10.7326/M20-3234 Google Scholar7. Lyu W, Wehby GL. Community use of face masks and COVID-19: evidence from a natural experiment of state mandates in the US. Health Aff (Millwood). 2020;39:1419-25 [PMID:32543923] doi:10.1377/hlthaff.2020.00818 Google Scholar8. Chan NC, Li K, Hirsh J. Peripheral oxygen saturation in older persons wearing nonmedical face masks in community settings. JAMA. 2020. [PMID:33125030] doi:10.1001/jama.2020.21905 Google Scholar Comments 0 Comments Sign In to Submit A Comment Stephen B. Strum, MD, FACPPrivate Community Practice of Hematology/Oncology18 November 2020 Source Control vs Protective Effect Laine et al. provide important insights relating to the publication by Bundgaard et al. My THLs (Take Home Lessons) from these papers relates to an old saying from my grandmother: "one hand washes the other". In other words, the person infected with SARS-CoV-2 wearing a mass may equate with "source" control which, along with social distancing could provide key elements in preventing transmission of the virus. In lieu of source control, the individual wearing a mask for protection may be interacting with others under the false assumption that wearing a mask has a protective effect. For me, an immunocompromised elderly individual, I should not feel at all comfortable with others approaching me who are not wearing a mask or lower their mask to talk, since the protective effect of a mask is now unproven. The bottom line is that it likely takes "two to tango" or both source & recipient; along with social distancing. This is highly valuable information while waiting for other well-designed studies to be published in peer-reviewed journals. Martin HaasTertiary care hospital, Austria19 November 2020 Data interpretation These data match the - non randomized- experience in Austria, where no association between the recommendation of mask wearing and Covid-19 infection can be found. If the first randomized study shows no effect of mask wearing in public, it is counterproductive to reject this information and twist the results to the opposite. It would be much more effective to accept the information and investigate other and better means for infection control. Robert SantellaAvera McKennan Hospital18 November 2020 Misuse of the data Unfortunately this study will be used politically to promote the argumnent that mask wearing is ineffective against the spread of COVID19. Kenneth H. Wilson, MD, FACP, FIDSADuke University Medical Center18 November 2020 The kind of mask makes a difference. The results of this study should come as no surprise given the reproducible results showing that cloth and surgical masks leak around the edges and inefficiently filter small particles (1-3). Duckbill and conical designs are more effective (2,3) and using an efficient filtration material in such facepieces can lead to relatively high efficiency. Public health recommendations are driven by a shortage of N95 and equivalent respirators, which would almost certainly benefit the public if they were available. Our culture should be capable of producing enough N95’s but short of that, recommendations should at least stress better mask design. 1. Sickbert-Bennett EE, Samet JM, Clapp PW, Chen H, Berntsen J, Zeman KL, et al. Filtration Efficiency of Hospital Face Mask Alternatives Available for Use During the COVID-19 Pandemic. JAMA Internal Medicine. 2020;11:11.2. Teesing GR, Straten BV, Man P, Horeman T. Is there an adequate alternative for commercially manufactured face masks? A comparison of various materials and forms. Journal of Hospital Infection. 2020;04:04.3. Mueller AV, Eden MJ, Oakes JM, Bellini C, Fernandez LA. Quantitative Method for Comparative Assessment of Particle Removal Efficiency of Fabric Masks as Alternatives to Standard Surgical Masks for PPE. Matter. 2020;3(3):950-62. Nicolas Feldreich MD, PhD, Senior C. An-Intensive CareHelse Fonna19 November 2020 The Evidence of an Vaccine Like Effect of Surgical Mask Is Present The well-crafted study of Bundgaard et al. contains the evidence of a vaccine-like effect of masks, but the study design with a composite outcome measure fails to high-light it. I propose a stratified outcome measure acknowledging the dose reduction of the surgical mask, suggesting a reduction of severe disease in surgical mask users. When I look at masks as a mean to decreasing the exposure to the user and instead having a vaccine-like effect I find the following. First, looking at the study as a vaccine trial, we see that the group with surgical masks as a personal protection gear has IgM and IgG antibodies in the same numbers as the control group (Table 2.) But could the intervention protect from symptomatic Covid-19? The number of antibody negative participants in the beginning of the study in the group with surgical masks (n=1916), have fewer episodes of clinical SARS-CoV-2, PCR positive disease with no need for hospitalization (0) or with the need for hospitalization (5) compared to fifteen in the control group (n=2061), (5) episodes with symptomatic COVID-19 outside hospital and 10 episodes with the need of hospital care for COVID-19 [ p = 0.0435 ] Fischer’s exact test. Thus surgical mask may have a vaccine like effect with the same level of asymptomatic antibody producing disease, but with a lower degree of clinical disease. Based on the above post-hoc analysis of the Bundgaard study I suggest that we should acknowledge the variola like effects of surgical mask. Additional studies would be unethical. Disclosures: Owner of two minor companies within the health care and biotech sector, Seaneige AB and Feldreich Caro Ruiz AB without any conflicting interests. Max LonginMathematician (Dipl.Math), Denmark, private21 December 2020 1. Inconsistency of data and 2. Misinterpretation of the effect 1. None of the PCR-tests at study end was positive in the face mask group and only 5 PCR-tests were positive in both groups. Given the measured “infection” rates this is one in hundred thousands respectively one in a million. (proof1 below) One could argue that this perhaps may be partly due to problems in self-PCR-testing or decreasing infection rates during study. I agree, but if one defends the results with noise then one cannot at the same time persistently ignore noise from false positive antibody tests and antibody-test detected before-baseline infections. To be clear this only shows that the study seems more than likely to measure for the most noise, it doesn’t show that the maximum likelihood estimate for the personal protection is wrong. 2. But given the mentioned estimate of 84% (instantaneous) personal protection the conclusion that “Contribution of masks to risk reduction in the community through personal protection is likely to be small” completely disregards the game changing epidemiological effect of a 90% risk reduction within 2 months in the community by personal protection alone. (proof2 below) The misuse of the study by face mask opponents could have at least been contained by not disregarding this striking epidemiological effectiveness in a study on the “Effectiveness ...” and by not mixing up “(instantaneous) personal protection” and “risk reduction in the community” in the editorial on hand. (Proof1) On an average PCR tests show an infection on at least 8 days (about day 21-28 of the study) with an almost 100% sensitivity. Given empirical probability of 1.8% in the face mask group to be infected within 30 days leads to a probability of p=0,018/30*8=0.0048 to be infected within 8 days for any of the 2392 participants of the face mask group. Bernoulli distribution shows that the chances for 0 positive PCR tests is F(0;2392;0.0048)=0.00001 and for the group “all” (1,95% in 30 days, n=4862) the chances for ≤5 positive PCR-tests is F(≤5;4862;0.0052)=0.000001 (Proof2) Within 3 weeks the number of infections in a community with a 82% personal protection would be 45% compared to a kindred community without this protection (0,824=0.45, 4 cycles of infection=20 days). It would be <10% (0,8212<0.1) within 2 months (12 cycles). This is only due to the supposed protection effect - assuming the same effect from source control on top you it would be 20% (0,828) risk of infection within 3 weeks and <1% (0,8224) within 2 months. Author, Article, and Disclosure InformationAuthors: Christine Laine, MD, MPH; Steven N. Goodman, MD, MHS, PhD; Eliseo Guallar, MD, MPH, DrPHAffiliations: Editor in Chief, Annals of Internal Medicine Stanford University School of Medicine Stanford, CaliforniaDeputy Editor, Statistics, Annals of Internal Medicine Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7448.Corresponding Author: Christine Laine, MD, MPH, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, claine@acponline.org.Current Author Addresses: Dr. Laine: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.Dr. Goodman: Stanford University School of Medicine, 150 Governor's Lane, Room T265, Stanford, CA 94305.Dr. Guallar: Departments of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health, 2024 East Monument Street, Room 2-645, Baltimore, MD 21205.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 byUnpacking Cochrane’s Update on Masks and COVID-19Getting to the Truth About the Effectiveness of Masks in Preventing COVID-19Christine Laine, MD, MPH, and Stephanie Chang, MD, MPHAssociation between face mask use and risk of SARS-CoV-2 infection: Cross-sectional studyEvaluation of different types of face masks to limit the spread of SARS-CoV-2: a modeling studySocial Values, Face Masks, and COVID-19: An Exploratory Case StudyOfeleein i mi Vlaptin—Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 PandemicCOVID-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?ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTIONS DURING THE COVID-19 PANDEMIC WITH IMPLEMENTATION OF UNIVERSAL MASKINGPolicy makers must act on incomplete evidence in responding to COVID-19 March 2021Volume 174, Issue 3 Page: 419-420 Keywords COVID-19 Disclosure Hygiene Observational studies Odds ratio Polymerase chain reaction Prevention, policy, and public health Randomized trials Research design Social distancing ePublished: 18 November 2020 Issue Published: March 2021 Copyright & PermissionsCopyright © 2020 by American College of Physicians. 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