In the Journal of General Internal Medicine, Monica Gandhi, professor of medicine and infectious disease specialist at the University of California at San Francisco, discusses for the first time 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. Asymptomatic infections, she says, maybe harmful for spread but could be beneficial if they lead to higher rates of exposure. In a world where more than two crore people have been infected with the novel coronavirus, what struck Gandhi was why so many more escaped practically unscathed, including those who had come in close contact with people who contracted COVID-19. Excerpts from the interview:
Q. You say that a high rate of asymptomatic infection is a good thing
Yes, a high rate of asymptomatic infection in COVID-19 can be a good thing. This virus has very protean manifestations, ranging from having no symptoms to severe disease and death. The Centre for Diseases Control and Prevention (CDC) in the US in mid-July estimated the rate of asymptomatic infection with COVID-19 to be 40 per cent. Although the asymptomatic infection can be a problem, since people who are well but infected can still spread the disease, a high rate of asymptomatic infection can be a good thing for individuals. Getting infected but never getting sick is a good outcome for a patient. Moreover, if individuals develop immunity to COVID-19 after asymptomatic infection, that helps slow down the spread of the disease since higher population-level immunity will lead to decreased spread. There is accumulating evidence that cell-mediated immunity develops after asymptomatic infection. There are two arms to the immune response – antibodies and cell-mediated immunity. Cell-mediated immunity provides long term protection and, if this develops to asymptomatic infection, is a very good outcome.
Q. You talk of universal public masking for pandemic control
The main finding of our study is that there are increasing bodies of evidence in three domains- virologic, epidemiologic, and ecologic – that masks reduce the viral inoculum or dose someone inhales in, lessening the severity of the disease. For COVID-19, it means that masks protect the individual and drive up the rate of asymptomatic infection. This is good since we want less severe disease and a more benign course for COVID-19. The virologic evidence is outlined in the article but we have papers dating back to 1938 on the relationship between viral inoculum and severity of the disease. More the virus gets in a host, the sicker the host gets. This has been shown with influenza A in human volunteers in 2015. In a hamster study, animals given higher inoculum of the virus had more severe disease than those given lower inoculum of the virus. In a recent study simulating masking for hamsters, the hamsters who got exposed to COVID-19 who ‘masked’ were less likely to get COVID-19 and, if they did, they got a mild disease. The epidemiologic evidence in settings that mask (like cruise ships) show that masking drives up the rate of asymptomatic infection. For instance, in cruise ship outbreaks from the beginning where we didn’t know about masking, the rate of asymptomatic infection was 18 per cent. In an Argentinian cruise ship where all the passengers and staff masked, 81 per cent of those who became infected were asymptomatic. And in countries that mask, the rate of severe disease is very low. Therefore, masking is one of the most important pillars to fight the pandemic – they protect you and they protect others. In India, if there are very crowded environments, wearing comfortable facial masks (simple cotton masks) at home would have benefit in reducing the frequency of severe illness. Finally, I think one of the most important things in this study is that driving up the rate of asymptomatic infection may also lead to greater immunity to the infection. Facial masks seem to reduce the viral inoculum or dose to which the wearer is exposed, leading to more and more asymptomatic infection. Benefits of masking against asymptomatics are to protect others because people without symptoms (asymptomatic) with COVID-19 can shed virus from their nose and mouth at high rates even when they feel well. To decrease the rate of getting the virus from blocking viral particles to getting into your mouth and nose. The third reason is what we talk about in terms of viral inoculum.
Q. It is said that the virus has a mild impact on children. What do you think that is telling us?
This is an interesting virus in that it seems to have a milder impact in children than in adults. Children are much less likely to become ill, possibly due to reduced expression of a receptor (called the ACE2 receptor) in the lining of their noses that takes in the virus. Children’s immune responses may be better equipped to fight the virus. I believe the milder impact on children means we should protect the adults around them, specifically teachers, by universally facial masking teachers and students as we open schools.
Q. Do age and genetics play a role, in some showing no symptoms at all while others dying from the illness?
Disease manifestations from a virus is always an interplay between host and virus. Individuals who are older or have certain blood types or who are immunocompromised may be more likely to get ill from SARS-CoV-2, the virus that causes COVID-19. However, we have been researching how the viral “dose” or inoculum seems to matter a lot when explaining how sick someone gets from this virus which is why facial masks— which filter out a majority of the viral particles— likely leads to less severe disease if the person becomes infected. Facial masks thus protect the mask-wearer ad those around him/her.
Q. So does this mean that some humans have immunity against the virus right from the beginning when it was termed as a novel virus?
Yes. Emerging data is showing us that many individuals may have T-cells (or a cell-mediated immune response) that developed in response to other common coronaviruses that cause the common cold. These T-cells, which emerged in response to another virus, seem to have a “cross-reacting” potential or ability to fight off this novel coronavirus, the one which causes COVID-19. Therefore, there is a certain segment of the population that seems to have some natural immunity to SARS-CoV-2, leading them to have a more mild disease or asymptomatic infection if they become infected with this novel coronavirus.
Q. Is there something called as pre-existing immunity in certain individuals that keeps them from the virus?
Yes, the idea is that – by being exposed to other viruses in the past (like the virus that causes the common cold)—we have developed T-cells or immune cells that can partially protect us against this new coronavirus that causes COVID-19. Moreover, our research is compiling data that getting even asymptomatic infection with COVID-19 may allow cell-mediated immunity to develop, leading to greater population-level immunity to this new virus, which will naturally slow down the spread.