No clear benefit with face coverings found in controversial Danish trial, but results are hardly definitive

“My mask protects you, your mask protects me.” It’s become the hallmark pandemic announcement, featured on social media, and invoked by health officials in “Stop the Spread” campaigns. But recent data out of Denmark would seem to fly in the face of that mantra: “A recommendation to wear a surgical mask when outside the home among others did not reduce, at conventional levels of statistical significance, incident SARS-CoV-2 infection compared with no mask recommendation,” according to researchers.

In the DANMASK-19 randomized control trial, a group of participants wearing a mask while outside the home to limit infection with SARS-CoV-2 had 0.3 percentage point (95% CI −0.4 to 1.2 percentage point, P=0.38) fewer SARS-CoV-2 infections than did a no-mask control group, according to Henning Bundgaard, DMSc, of Rigshospitalet in Copenhagen, and co-authors.

Infection with SARS-CoV-2 occurred in 1.8% of participants who were advised to wear masks and 2.1% in the control group (odds ratio 0.82, 95% CI 0.54 to 1.23, P=0.33), they reported in the Annals of Internal Medicine.

In one of two editorials accompanying the study, Christine Laine, MD, MPH, of Jefferson University Hospitals in Philadelphia, and co-authors wrote “We must emphasize that this trial does not address the question about transmission in communities where most people wear masks and does not disprove the effectiveness of widespread mask wearing.”

They pointed out that the CDC “recently updated its guidance to acknowledge that masks, when worn by all, may reduce transmission via both source control and personal protection. 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… does not make the wearers invulnerable to infection.”

Laine, who serves as the editor-in-chief of Annals of Internal Medicine, and co-authors acknowledged that some may call the journal “irresponsible” for publishing the DANMASK-19 results. “We think not,” they argued. “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.”

In fact, Bundgaard’s group also pointed out that “Although no statistically significant difference in SARS-CoV-2 incidence was observed, the 95% CIs are compatible with a possible 46% reduction to 23% increase in infection among mask wearers.”

“These findings do offer evidence about the degree of protection mask wearers can anticipate in a setting where others are not wearing masks and where other public health measures, including social distancing, are in effect,” they emphasized.

Whether their caveats will make the “no-mask” crowd do an about face — or talk up the results to save face — is still uncertain, especially in the U.S., where mask wearing has become “a hot-button political issue. [Masks] are increasingly a badge symbolizing who one voted for. This is a terrible consequence of bad leadership and caustic, polarized social media posts — yes, unfortunately, by both proponents and opponents of masks,” noted Vinay Prasad, MD, MPH, of the University of California San Francisco, in a MedPage Today opinion piece.

The trial took place from April 3 to June 2, 2020, a time period in which Danish authorities did not recommend use of masks in the community, and mask use was reported at <5% outside hospitals, according to Bundgaard’s group. However, public health measures at the time did call for quarantining after a positive Covid-19 test, social distancing when in public, limiting contacts outside the home, and frequent hand hygiene and cleaning. Cafés and restaurants were closed in the country until May 18, 2020.

Eligible participants for the study were community-dwelling adults without current or prior symptoms, or diagnosis of Covid-19. They self-reported being outside the home at least 3 hours/day and did not wear a mask during their daily work.

Disposable surgical masks (50 total) were provided to each intervention participant, who were asked to wear a new mask each day outside the home for a 1-month period.

Participants were tested for SARS-CoV-2 IgM and IgG antibodies in whole blood using a point-of-care test and were categorized as seropositive if they developed IgM, IgG, or both as a test result.

A cohort of 3,030 participants were randomly assigned to wear face masks (mean age 47.4; 64.6% female, 80.1% provided antibody test at baseline), and 2,994 were assigned to the control group (mean age 47, 63.6% female; 83.4% provided antibody test at baseline). Of these, 80.7% completed the study, and they reported spending a median of 4.5 hours/day outside the home.

The fact that women made up 60% of study participants is an issue, as women may be more likely to adhere to public health recommendations than men, according to Thomas R. Frieden, MD, MPH, and Shama Cash-Goldwasser, MD, MPH, both of Resolve To Save Lives in New York City. Frieden is a former CDC director.

In their accompanying editorial, Frieden and Cash-Goldwasser pointed out that among the female participants, the decreased odds of infection with SARS-CoV-2 in the intervention group approached statistical significance versus the control group (OR 0.65, 95 CI% 0.38-1.12).

Bundgaard and co-authors reported that, based on the lowest adherence reported in the mask group during follow-up, 46% of participants wore the mask as recommended, 47% predominantly as recommended, and 7% not as recommended. The trial’s primary outcome was infection with SARS-CoV-2, defined as positive results of lateral flow testing for anti–SARS-CoV-2 IgM or IgG antibodies at 1 month; positive results of polymerase chain reaction testing for SARS-CoV-2 at 1 month and symptoms compatible with Covid-19; or diagnosis of Covid-19 by a healthcare practitioner. The primary outcome occurred in 1.8% of participants in the intervention group and 2.1% in the control group.

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Study limitations included inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others.

The trial’s small study population was also problematic, according to Frieden and Cash-Goldwasser. They explained that the data demonstrated that across all analyses, the odds ratios overall were approximately 0.8, consistent with a 20% reduction in incident SARS-CoV-2 infection if masks are recommended. “However, the sample size was insufficient to determine the statistical significance of a 20% reduction,” they stated.

They also suggested that “The specifics of the study setting limit not only its statistical power but also the generalizability of findings,” as it was done in a setting with relatively low transmission. In week 1 of May 2020, the daily incidence of new confirmed Covid-19 cases in Denmark was roughly one-third of that in the U.K. and a quarter of that in the U.S., they noted.

Frieden and Cash-Goldwasser also took the trial to task for being underpowered for subgroup analyses by occupation, time out of home (although more time out of home was associated with a greater trend toward protection), and other factors.

“Thus, the potential benefit of mask wearing in particular circumstances or settings could not be assessed,” they wrote.

Comments on the study on the Annals website ranged from decrying the way the results are presented — “anti-maskers are using this study as ’prof’ [sic] that they don’t need to wear masks. This is irresponsible and should be made clear in the title of the study,” wrote Janet Rand, OD, a U.S.-based optometrist — to supportive criticism: “The effort by Dr. Bundgaard and colleagues is commendable. However, the trial design and the associated results remind me of the randomized controlled trials assessing the efficacy of a ’prayer’ intervention. The fundamental issue with mask intervention and social distancing, like prayer, is the lack of objective mechanisms to ensure and track compliance or non-compliance (lack of an accurate method to track who is praying or not praying),” opined Ambuj Kumar, MD, MPH, of Morsani College of Medicine at the University of South Florida in Tampa.

Perhaps as a take-home message, Laine’s group cautioned that “All who worry about the Covid-19 pandemic should… refrain from viewing [the results] 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.”

  1. A recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a Danish community with modest infection rates, some degree of social distancing, and uncommon general mask use.

  2. Editorialists commenting on the study called it “underpowered” for subgroup analyses, and while the results could be viewed as evidence that widespread mask-wearing is ineffective, they do offer evidence about the degree of protection with mask wearing in a setting where other public health measures are in effect.

Shalmali Pal, Contributing Writer, BreakingMED™

The study was funded by The Salling Foundations.

Bungaard reported no relationships relevant to the contents of this paper to disclose. Co-authors reported relationships with, and/or support from, the Novo Nordisk Foundation, the Simonsen Foundation, GlaxoSmithKline, Pfizer, Boehringer Ingelheim, Gilead, MSD, Lundbeck Foundation, the Kai Hansen Foundation, Novo Nordisk, and Bayer.

Laine reported serving as senior vice-president of the American College of Physicians.

Frieden and Cash-Goldwasser reported no relationships relevant to the contents of this paper to disclose.

Cat ID: 190

Topic ID: 79,190,254,930,728,791,932,730,933,190,926,192,927,151,928,925,934