Volume 8 • 2021 • Issue 2

LEARNING FROM COVID-19 different people’s cells to try and understand how the virus may rewire or change the circuitry within our cells that allows them to function normally. This also includes how the cells of younger people respond to the virus compared to older people, since we know that age correlates with disease severity. In the lab, we look at human cells in our in vitro cell culture work. This lets us look at some of these biological phenomena in very specific settings, for example specific cell types that are found in the lungs. We also look at animal models of infection, primarily in hamsters, as our work in cells can’t necessarily recreate all of the biological complexity that is found in a living organism. This includes all of the individual cells and components of our immune system, the interactions between different cell types within tissues or between different organs. Q How is COVID different from coronaviruses of the past? JK : We’ve known about coronaviruses for close to 60 years now. In 2003, SARS emerged as this new virus that quickly became an epidemic and had a profound impact on Canada, primarily Toronto. Then in 2012, the Middle East respiratory syndrome (MERS) coronavirus was first identified in humans. Both viruses can be transmitted directly between people, though these transmission events were primarily limited to hospital settings with little community transmission. COVID-19 is different because SARS-CoV-2 can be widely transmitted between people in our communities. Although we see community transmission with other respiratory viruses like influenza viruses, influenza spreads in a fairly homogenous fashion from one person to another; most people who get the flu give it to the same number of people as other people who have the flu. With COVID, 80% of infections are largely driven by 10 to 20% of infected people, which has led to “super- spreader events” where we see very broad dissemination of virus to a much larger group of people than normal for this virus. However, the factors that relate to super-spreader events (biological or environmental) have remained elusive. Why is this virus behaving so differently? Its genome is very similar to other coronaviruses. In the lab, most of its behaviours, both in cells and in animals, are similar to other coronaviruses, so it’s confounding. We are beginning to figure out how molecular interactions between the virus and a cell may facilitate the differences between say SARS-CoV and SARS-CoV-2, for example. Q When I think about superspreader events I assumed that it was caused by behaviour, like not wearing a mask or going to a party. But are you suggesting that there is something different biologically? JK : The unfortunate reality of understanding emerging viruses is that nothing can be explained by just one variable. It would be much easier if we could just say, “If we don’t have people close together in enclosed settings with low ventilation, superspreader events wouldn’t exist.” That would take care of a large portion of the causes, but likely not completely stop these occurrences. There are likely underlying characteristics in certain people that cause them to easily transmit the virus. Maybe they release more copies of the virus. Maybe they generate more or smaller aerosols that hang in the air longer. Looking at the animal models, there is data to support roles for both droplets and aerosols in transmission, but we don’t know if there’s a relation between the proportion of these that are released from an infected person and whether this is related to super-spreader events. And we also have to appreciate that animal models of infection and transmission likely don’t completely recapitulate the complexity of human- to-human transmission. We are certainly still learning. Q What can we expect to learn from COVID-19 research in the coming year? JK : COVID-19 has really changed the research playing field, in a good way. The first genome sequences of the virus were generated in early January 2020, and the public release of these allowed people across the globe to quickly analyze the viral genome and identify what had emerged. Researchers from around the world, independent of nationality or political affiliation, have continued to keep very open lines of communication. Consider that in 12 months following the initial emergence of a brand new virus, we have seen the licensing of multiple vaccines that are being distributed across the globe. All of this was reliant on the sharing of data and transparency across the global research community. This is historically unprecedented. We've learned about a decade’s worth of information about the virus in just one year! Once we have the pandemic more under control using the vaccines, we’ll likely see controlled studies that will help with the nuanced questions that we still have about the virus and its transmission. We’ll learn conclusively if touch surface transmission is something to worry about. With COVID, 80% of infections are largely driven by 10-20% of infected people which has led to “superspreader events.” However, the biological or environmental factors that relate to these events have remained elusive. 33 Issue 2 | 2021 |