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

Corresponding Author:
1

Monica 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: monica.gandhi@ucsf.edu

2

Chris 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
cbeyrer@jhu.edu

3

Eric 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: monica.gandhi@ucsf.edu

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 Abstract word count: 200

Manuscript Word Count: 1296

Number of references: 49

Number of figures: 1

ABSTRACT
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 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
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 asymptomatic disease with SARS-CoV-2 in light of population-level masking has
received little attention so this is one of the first perspectives to discuss the
evidence supporting this theory.

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 populationlevel 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
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 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 lessstringent 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 U.S. states) 7 issuing mandates and enforcement
strategies.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.
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 – or the dose
that leads to severe disease or death- for a variety of viruses in hosts or animal
models.17,21,29-34
These studies have limitations, since experiments to examine the dose of
virus to achieve its LD50 have necessarily not been conducted in humans. Studies

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 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
Increasing rates of asymptomatic and mild infection with COVID-19 have
been seen over time during the pandemic in settings adopting population-level
masking. A systematic review of earlier studies, before facial masking was widely
practiced, placed the proportion of asymptomatic infection with SARS-CoV-2 at
15%.35 A more recent narrative review of 16 different studies estimated the rate of
asymptomatic infection at 40-45%.36 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.37 In a more recent report from a different cruise ship
outbreak, all passengers were issued surgical masks and all staff provided N95
masks after the initial case of COVID-19 on the ship was detected. 38 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

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 (81%) remained asymptomatic,38 compared to 18% in the cruise ship outbreak
without masking.37
A report from a pediatric hemodialysis unit in Indiana, where all patients and
staff were masked, demonstrated that staff rapidly developed antibodies to SARSCoV-2 after exposure to a single symptomatic patient with COVID-19. In the setting
of masking, however, none of the new infections were symptomatic. 39 And in a
recent outbreak in a seafood processing plant in Oregon where all workers were
issued masks each day at work, the rate of asymptomatic infection among the 124
infected was 95%.40,41 Finally, in a mass testing campaign to assess the prevalence
of COVID-19 in the Mission District of San Francisco, the majority of those who
tested positive via RT-PCR ( >50%) were asymptomatic. 42 This testing campaign was
performed in a city that had mandated population-level public masking a week
earlier.43
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)44,
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, 45 have
fared well in terms of rates of severe illness and death. Indeed, even when cases

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 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,46 which is suggestive of this viral inoculum theory.
Although asymptomatic infection can be problematic in terms of increasing
spread,4 it can also be beneficial.14 Higher rates of asymptomatic infection with
SARS-CoV-2 lead to higher rates of exposure, as was seen with antibody testing
campaigns in Japan47 or the surveillance study in the pediatric hemodialysis unit in
Indiana.39 Exposing society to SARS-CoV-2 without the unacceptable consequences
of severe illness could lead to greater community-level immunity 48 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 T-cell immunity, even with mild disease, is increasingly hopeful. 49,50 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),51 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

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 for the individual and will allow for the preservation of life, along with other COVID19 control measures, as society re-opens. This perspective puts forth another
advantage of population-level facial masking for pandemic control with SARS-CoV-2
based on an old but enduring theory 18 regarding viral inoculum, clinical
manifestations in the host, and protection.
Figure 1a: Busy Hong Kong Street on May 14, 2020 demonstrating universal public
masking44; 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 pandemic 51

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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.)

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