Maske Takan da Bulaştan Korunuyor

Tem 29, 2020
Maske Takan da Bulaştan Korunuyor

Journal of General Interenal Medicine’da Ağustos 2020 için yayına kabul edilen bir makale, şimdiye dek çok tartışılan ve maske kullanımının sadece hasta olan kişilerden diğerlerine bulaşı engellediğini öne süren görüşe ek olarak maske takanın da bulaştan korunduğuna dair bilimsel kanıtları veriyor.


Masks Do More than Protect Others during COVID-19: Reducing the Inoculum of SARS-CoV-2


Monica Gandhi, MD, MPH1, Chris Beyrer MD, MPH2, Eric Goosby, MD1


Running title: Masks Reduce Viral Inoculum of SARS-CoV2

In press, Journal of General Internal Medicine (August 2020)



Corresponding Author:

1Monica Gandhi, MD, MPH

Professor of Medicine, University of California, San Francisco (UCSF)

Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, 995 Potrero Avenue, 4th Floor

San Francisco, CA, 94110

Email address:


2Chris Beyrer MD, MPH

Desmond M. Tutu Professor of Public Health and Human Rights Johns Hopkins Bloomberg School of Public Health

615 N. Wolfe Street Suite E7152

Baltimore, Maryland 21205


3Eric Goosby MD

Professor of Medicine, University of California, San Francisco (UCSF)

Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, 995 Potrero Avenue, 4th Floor

San Francisco, CA, 94110

Email address:





Although the benefit of population-level public facial masking to protect others during the COVID-19 pandemic has received a great deal of attention, we discuss for one of the first times the hypothesis – compiling virologic, epidemiologic and ecologic evidence- that universal masking reduces the “inoculum” or dose of the virus for the mask-wearer, leading to more mild and asymptomatic infection manifestations. Masks, depending on type, filter out the majority of viral particles, but not all. We first discuss the near-century old literature around the viral inoculum and severity of disease (conceptualized as the LD50 or lethal dose of the virus). We include examples of rising rates of asymptomatic infection with population-level masking, including in closed settings (e.g. cruise ships) with and without universal masking. Asymptomatic infections may be harmful for spread but could actually be beneficial if they lead to higher rates of exposure. Exposing society to SARS-CoV-2 without the unacceptable consequences of severe illness with public masking could lead to greater community-level immunity and slower spread as we await a vaccine. This theory of viral inoculum and mild or asymptomatic disease with SARS-CoV-2 in light of population-level masking shows the benefits of mask-wearing for the individual (as well as others) as a pillar of COVID-19 pandemic control.





This perspective outlines a unique angle on why universal public masking during the COVID-19 pandemic should be one of the most important pillars of disease control. Our theory is based on the likelihood of masking reducing the viral inoculum to which the mask-wearer is exposed, leading to higher rates of mild or asymptomatic infection with COVID-19. No prior perspective has specifically focused on this link between population-level facial masking, the viral inoculum, and increasing rates of asymptomatic infection with SARS-CoV-2.


On April 3, 2020, the Centers for Disease Control and Prevention issued recommendations on wearing cloth face coverings by the public to reduce community spread.1 The World Health Organization did not recommend population-level face masking in April,2 but changed their guidance on June 5, 2020,3 when the extent of transmission from pre-symptomatic or even asymptomatic individuals was clear.4,5 One recent model showed that population-level masking is one of the most efficacious interventions to reduce further spread of SARS-CoV-2, allowing for less-stringent lock-down requirements in countries adopting this strategy.6 Countries worldwide have had a range of responses to the recommendation on universal masking, with many countries (and some U.S. states)7 issuing mandates.8 Countries accustomed to universal population-level masking since the SARS epidemic in 2003 adopted the intervention more readily.9


There are two likely reasons for the effectiveness of facial masks: The first – to prevent the spread of viral particles from asymptomatic individuals to others – has received a great deal of attention.10,11 However, the second theory- that reducing the inoculum of virus to which a mask-wearer is exposed will result in milder disease12-27 -has received less attention and is the focus of our perspective. There are three major bodies of evidence we examined when formulating this theory: virologic, epidemiologic and ecologic.


Virologic evidence



Masks, depending on the material and design, filter out a majority of viral particles, but not all.28 The theory that exposure to a lower inoculum or dose of any virus (whether respiratory, gastrointestinal or sexually-transmitted) can make subsequent illness far less likely to be severe12-27 has been propounded for some time. Indeed, the concept of the 50% lethal dose (LD50), the virus dose at which fifty percent of exposed hosts die, determined via controlled experiments in which a range of exposure doses are administered to animals to calculate a dose-mortality curve, was first described in 1938.18 Other studies have examined the LD50, the dose that leads to severe disease or death, or ID50, the median dose at which 50% of a population gets infected, for a variety of viruses in hosts or animal models.17,21,29-35


These studies have limitations, since experiments to examine the dose of virus to achieve its LD50 have necessarily not been conducted in humans. Studies to experimentally examine the dose of virus associated with different levels of diseases severity in humans has been limited to non-lethal viruses. In one experiment in preparation for vaccine development, healthy human volunteers exposed to different doses of wild-type influenza A virus developed more severe symptoms at higher inocula of administered virus.34 Giving SARS-CoV-2 in a range of doses to humans experimentally would be unethical, but an animal model has tested this theory of masking attenuating disease severity. In a frequently-cited study showing that hamsters are less likely to contract SARS-CoV-2 infection with a surgical mask partition, those hamsters that did contract COVID-19 with simulated masking had milder manifestations of infection.27


Epidemiologic evidence from outbreaks



Crowding and exposure to higher viral inocula seems to be associated with more symptoms with SARS- CoV-2 and likely contributed to the higher mortality rate of COVID-19 earlier in the pandemic prior to


masking. Increasing rates of asymptomatic and mild infection with COVID-19 have been seen over time during the pandemic in settings adopting population-level masking. In one study among two Swiss cohorts of soldiers, the cohort who employed social distancing or facial masks had no illness after a COVID-19 outbreak, compared to a 30% illness rate in an outbreak under typical conditions.36. A systematic review of earlier studies, before facial masking was widely practiced, placed the proportion of asymptomatic infection with SARS-CoV-2 at 15%.37 A more recent narrative review of 16 different studies estimated the rate of asymptomatic infection with COVID-19 at 40-45%;38 this rate of 40% asymptomatic infection with SARS-CoV-2 was recently endorsed by the CDC.39 Closed settings, such as cruise ships, can be particularly illustrative when examining phenotypes associated with SARS-CoV-2.

For example, one of the earliest estimates of the rate of asymptomatic infection due to SARS-CoV-2 was in the 20% range from a report of a COVID-19 outbreak on the Diamond Princess cruise ship.40 In a more recent report from a cruise ship outbreak in Argentina, all passengers were issued surgical masks and all staff provided N95 masks after the initial case of COVID-19 on the ship was detected.41 In this closed setting with masking, where 128 of 217 passengers and staff eventually tested positive for SARS-CoV-2 via RT-PCR, the majority of infected patients on the ship (81%) remained asymptomatic,41 compared to 18% in the cruise ship outbreak without masking40 and 40% as the typical rate.39


A report from a pediatric hemodialysis unit in Indiana, where all patients and staff were masked, demonstrated that staff rapidly developed antibodies to SARS-CoV-2 after exposure to a single symptomatic patient with COVID-19. In the setting of masking, however, none of the new infections were symptomatic.42 In two recent outbreaks in a seafood processing plant in Oregon and a chicken processing plant in Arkansas, where all workers were issued masks each day at work, the rates of asymptomatic infection among the over 500 individuals who became infected were both 95%.43,44 In a hair salon outbreak from an infected hair stylist where masking was implemented in Missouri, none of the clients tested (n=67) became infected and the remainder (n=72) remained asymptomatic.45 And


finally, universal masking in a Boston healthcare system reduced health care worker infection rates substantially.46,47


Ecologic evidence



One model showed a correlation between population-level masking and number of COVID-19 cases in various countries, but an even stronger correlation with suppression of COVID-related death rates.9 However, it should be acknowledged that this model could not account for all confounders that led to such low death rates in the regions examined. This group showed that, if 80% of the population wears a moderately effective mask, nearly half of the projected deaths over the next two months could be prevented.9 Countries accustomed to masking since the 2003 SARS-CoV pandemic, including Japan, Hong Kong (Figure 1a)48, Taiwan, Thailand, South Korea, and Singapore,9 and those who newly- embraced masking early on in the COVID-19 pandemic, such as the Czech Republic (who mandated masking early on March 23, 2020),49 have fared well in terms of rates of severe illness and death.

Indeed, even when cases have resurged in these areas with population-based masking upon re-opening (e.g. South Korea, Singapore, Hong Kong, Taiwan), the case-fatality rate has remained low with opening but masking,50 suggestive of this viral inoculum theory.


Benefits of driving rates of asymptomatic infection up with SARS-CoV-2 up



Although asymptomatic infection can be problematic in terms of increasing spread,4 it can also be beneficial.14 Asymptomatic infection, rather than severe illness, is beneficial for the individual.

Higher rates of asymptomatic infection with SARS-CoV-2 lead to higher rates of exposure, as was seen with antibody testing campaigns in Japan51 or the surveillance study in the pediatric hemodialysis unit in Indiana.42 Exposing society to SARS-CoV-2 without the unacceptable consequences of severe illness (e.g. a “poor man’s vaccine”) could lead to greater community-level immunity52 and slow down spread as we


await a vaccine. The level of effective antibody and T-cell immune responses to different manifestations of COVID-19 is still under study, although data for the development of cell-mediated immunity, even with mild disease, is increasingly hopeful.53,54 Monitoring for upticks in illness, not asymptomatic cases, could herald a need to re-enforce more stringent social distancing measures in a society which has adopted universal public masking going forward.





For this particular pillar of pandemic control to work in the U.S., leading politicians will need to endorse and model mask-wearing. The U.S. has embraced universal public masking before, during the 1918 Spanish influenza pandemic (Figure 1b),55 but the CDC recommendation made on April 3, 2020 for public masking due to COVID-19 has been unevenly followed.7 The efforts to preserve life must be balanced against the catastrophic consequences of shutting down economies, which ultimately will lead to more suffering, poverty and death than the virus itself, especially for the working poor. Although universal public masking can certainly protect others, the “inoculum” theory argues for a major protective effect for the individual and will allow for the preservation of life and less severe illness, along with other COVID-19 control measures, as society re-opens. This perspective puts forth another advantage of population-level facial masking (protecting the individual) for SARS-CoV-2 control based on an old but enduring theory18 regarding viral inoculum driving clinical manifestations, as well as epidemiologic observations for COVID-19 over time.





Figure 1a: Busy Hong Kong Street on May 14, 2020 demonstrating universal public masking48; only five deaths reported in Hong Kong from COVID-19


Figure 1b: Georgia Tech football game with fans wearing masks packed in a campus stadium in the midst of the 1918 influenza pandemic55





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CONFLICT OF INTEREST STATEMENT: None of the authors have any conflicts of interest to report


ACKNOWLEDGEMENTS: We would like to acknowledge all the brave health care workers fighting COVID-19. Funding source for this perspective: NIAID/NIH 2P30 AI027763 (Gandhi, P.I.)