#117 - Stanley Perlman, M.D., Ph.D.: Insights from a coronavirus expert on COVID-19

Stanley Perlman initially trained in cell biology, developmental biology, and virology, then went to medical school, becoming interested in pediatrics and infectious diseases. His research focused on how viruses interact with the brain, leading him to study coronaviruses in mice as a model for demyelination, similar to multiple sclerosis.

Coronaviruses are named for the crown-like or sun-like projections (corona) on their surface when viewed under an electron microscope. This distinctive appearance led early researchers to assign the name based on this visual characteristic.

The R-naught for SARS was estimated to be about two to three, meaning one infected person would typically infect two to three others. However, this average was misleading, as spread occurred much more readily within hospitals, especially during procedures that aerosolized lung fluids.

MERS did not cause a widespread epidemic because its human-to-human R-naught was very low, estimated between 0.35 and 0.5 outside of hospitals. This poor ability to spread between people, even with a high case fatality rate, made it relatively easy to contain, with most transmission occurring in healthcare settings.

The SARS outbreak was eradicated due to a combination of factors: there was no animal reservoir continuously reintroducing the virus to humans, and infected individuals were typically not contagious until they became symptomatic. This allowed for effective identification and quarantine of sick individuals, stopping the chain of transmission.

SARS-CoV-2 is described as a mixture of a common cold coronavirus and SARS/MERS in the lungs, allowing it to infect both the upper airway and the lungs. This upper airway infection contributes to its high transmissibility, even from asymptomatic individuals, unlike SARS-1 and MERS which primarily caused deep lung disease and were less contagious until severe symptoms appeared.

While not fully understood, survivors of severe COVID-19, like those from SARS and MERS, may experience lingering issues such as reduced lung function or cognitive dysfunction. These impacts could be due to permanent tissue damage, prolonged critical illness (e.g., ventilator use), or even immune-mediated neurological effects, even if the virus isn't directly found in the brain.

The exact reasons for reinfection with common cold coronaviruses are not fully understood, but it's known that the antibody response to these viruses wanes over time, often within a year. Specific antibodies like IgA also decline, and the role of T-cell responses in long-term immunity to these mild infections is not well-established.

So far, there is no strong evidence that SARS-CoV-2 is undergoing significant genetic drift that would make a vaccine ineffective or prevent protection from a previous infection. While some coronaviruses like OC43 show variation, SARS-CoV-2 has not yet demonstrated changes that would fundamentally alter its immune recognition.

Some studies suggest that people who have never been exposed to SARS-CoV-2 may have a T-cell response to it, potentially due to cross-reactivity from common cold coronaviruses. However, these findings are preliminary, often based on activation markers rather than direct killing function, and the homology between the T-cell targets is not always clear, so the importance of this cross-reactivity is still under investigation.

The ideal strategy for treating COVID-19 would involve a phased approach: antiviral therapy (like remdesivir or an oral form) early in the infection to stop viral replication, followed by immune modulators later in the disease course to address an overactive immune response. This approach requires better biomarkers to identify disease stages and tailor therapy effectively.