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Airborne transmission of SARS-CoV-2 remains one of the most critical questions to solve in terms of getting the COVID-19 pandemic under control, experts said on Wednesday.

With asymptomatic individuals believed to be responsible for close to half of new cases, viral transmission dynamics aren't yet fully understood, including how -- specifically, how far, for how long, and in what form -- infectious particles move through the air.

At a virtual workshop held by the National Academies of Science, Engineering, and Medicine entitled "," experts reviewed the data along with some historical context.

"One thing that has been very clear with this virus that is very troublesome and problematic is 40%-45% of individuals are infected without symptoms," said National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD.

He added that since asymptomatic individuals are "clearly documented" to transmit the virus person-to-person, this makes it "extremely difficult" to do isolation and contact tracing.

Fauci discussed the risk of COVID-19 transmission, which varies by the "type and duration of exposure, use of preventive measures, and individual factors," such as the amount of virus in respiratory secretions.

Indeed, understanding the mechanisms of transmission helps inform public health guidance, such as physical distancing, precautions in healthcare settings, ventilation in indoor environments, cleaning and disinfection practices, and "the forcefulness with which we recommend masking, which should be very strong," Fauci added.

Jonathan Samet, MD, of Colorado School of Public Health, compared emerging research on COVID-19 transmission to historical research on tuberculosis, the leading cause of mortality in the U.S. at the beginning of the 20th century. He reminded the viewers that tuberculosis was once thought to be a disease transmitted by "oral secretions," such as spitting, which is why cities put up spittoons to stop transmission.

But a "shift in paradigm" came from a study in 1956, which showed how guinea pigs were infected by airborne transmission of tuberculosis. The advice shifted from "don't spit" to wear a mask, isolate, and improve ventilation. Samet said that because we still refer to William Wells, MD, a co-author of the study, "and his ideas of airborne droplet nuclei" and how the infected range of droplets depends on how much time spent in the atmosphere "reveals how little progress we've made" in the years following the study.

Jay Butler, MD, of the CDC, reviewed how SARS-CoV-2 spreads by both droplet transmission, where infectious particles are "projectiles," and potentially, via airborne transmission, the so-called "infectious droplet nuclei," which remain airborne from minutes to hours and are spread by air currents.

But, he added, risk of person-to-person infectious disease transmission is complex, and driven by a number of factors. The latest research indicates that secondary attack rates are the greatest among household contacts (10%-40%), followed by sharing a meal (7%) and passing interaction, such as shopping (0.6%), though epidemiologic risk remains high in congregate settings, like workplaces, correctional facilities, homeless shelters, and bars.

Butler also presented a summary of unpublished data from a case-control study in 11 centers in 10 states of adults presenting with COVID-like illness. Researchers compared 154 adults testing positive for infection with 160 of those who tested negative, and interviewed them 2-3 weeks afterwards.

Of the cases, 42% said they had close contact with someone who had COVID-19 versus only 14% of the controls, Butler said. And among those reporting close contact with someone who had COVID-19, over half of cases said they had close contact with a family member (versus 22% of controls).

Cases were also more likely to have eaten in a restaurant in the last 14 days, and eaten in a restaurant that reported "few or no" people wearing masks versus controls, though interestingly, Butler said there was no difference in mask usage between the two groups. Other high-risk behavior, such as going to bars and coffee shops, using public transit, and attending church, was not assessed due to low prevalence of these practices in the group, he added.

He also cited the , with an 87% attack rate. Three participants were hospitalized and two died.

"Taken together, it does not prove the route of transmission is airborne, given the time and amount of people in the room," Butler said, adding, though, that the circumstantial evidence is "very intriguing" that "evidence of aerosol transmission may occur."

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