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Is the COVID-19 picture becoming clearer?

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As COVID-19 outbreaks continue to reach record highs across the United States, it appears we still have much to learn about the virus.

However, Michael Oglesbee, director of Ohio State’s Infectious Diseases Institute, explains that while we do still have plenty of questions, we’ve also gained many answers these past months.

What have we learned about COVID-19 since it emerged?

This virus is unique relative to previous emerging coronaviruses (i.e., SARS and MERS) in that it firsts replicates in the nasal cavity before descending into the lungs. This may account for the fact that it can be shed and transmitted to others before symptoms of lung infection develop. This can account for the high degree of contagion. When it does enter the lungs, we see an excessive inflammatory response that can account for severe disease and even death. The virus also infects the intestinal tract and can cause symptoms, although it is less clear what role this may play in transmission of infection.

But there are as many questions as answers. Once you have recovered from infection, are there long-term impacts on lung function? Why is mortality in men so much greater than women? Why are African Americans and Hispanics much more likely to develop severe health outcomes of infection?

This gets to the importance of understanding health conditions — for example, underlying heart disease — the influence of sex hormones, or genetic predisposition to severe health outcomes.

We know that the inflammatory syndrome extends well beyond the lungs to include other organs, such as the kidneys, and that we can see triggering of the blood clotting system that can result in stroke. We also know that the virus can trigger inflammation in the brain without actually being present in that location, and that it can also enter the brain. But we really don’t know how these events might be connected and the overall significance of some of these events.

This underscores the importance of not dismissing the significance of mild or asymptomatic infections.

Over time, we’ve seen some facts about the virus shift and change. Is this common when a new virus emerges?

I would not say that the facts are shifting or changing. It is more accurate to say that the picture is becoming clearer.

We learn by studying people who are infected and how they respond to treatment. We learn by studying how the virus is spreading in populations and the genetics of the virus as it spreads. We learn by studying growth of the virus in the laboratory, and by comparing what we know about other coronaviruses to what we are observing with SARS-CoV-2/COVID-19.

All of these must happen simultaneously to understand the biology of a new pathogen, highlighting the importance of interdisciplinary approaches, and we’ve made great progress in the past six months.

How much of what we know about coronaviruses in general helps us understand COVID-19?

Coronaviruses are common in multiple animal species. They are generally species-specific, but can evolve to infect other species. They may cause a spectrum of disease ranging from clinically insignificant to severe, often differing in their distribution in the body. Knowledge of these systems is a huge benefit in coming up to speed on the biology of SARS-CoV-2 in people.

The basic mechanisms of virus replication are essentially the same, so that studying a beta coronavirus of cattle at the cellular level can tell us a lot about what to expect with a beta coronavirus of humans.

Although no vaccine against a human coronavirus has ever been licensed, a coronavirus vaccine has been developed in chickens, protecting them from infectious bronchitis virus. So there is precedent for developing effective vaccines against coronaviruses, which is great news for our vaccine efforts.

How far along are we now in having a full understanding of COVID-19’s characteristics?

Understanding the basic biology of the virus is far along. It is the understanding of how the virus causes disease that is the challenge.

Knowing how the virus spreads within a human patient, the mechanisms by which it causes disease and how effective immune response is developed or not require the study of both human patients and particularly the study of animal models.

I would say this aspect is in development — making good progress, but we have much to learn.

"Coronaviruses are common in multiple animal species."
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Michael Oglesbee, director of Ohio State’s Infectious Diseases Institute
Have we learned anything about this virus that may help us in the future with similar viruses?

This gets back to the ‘picture is coming into view’ response. We know we have a respiratory-enteric coronavirus, and it can elicit a multi-systemic inflammatory response. It is the result of a spillover event. We will ultimately establish a vaccine.

So think of this as a mosaic — distinct challenges with distinct solutions. As we learn about individual pieces of the COVID-19 puzzle, they may help us down the road — in knowing how to anticipate/disrupt a future spillover event, in knowing how to treat a severe acute respiratory syndrome (caused by any number of agents), in knowing how to rapidly develop a safe and effective vaccine against a new coronavirus — to name a few.

How should we address asymptomatic people or COVID-19 carriers?

Overall, approximately 40 to 45% of people infected with SARS-CoV-2 will not develop symptoms, with the percentages varying as a function of age group. For people aged 20 and under, we may see symptoms only 20% of the time. The challenge is twofold.

First, people shed virus for up to two days prior to developing symptoms, and this is a major source of transmission in a population. We call this the pre-symptomatic phase.

Secondly, people who never will develop symptoms can still shed and transmit the virus to others. As such, asymptomatic infections must be identified if we are to contain outbreaks of COVID-19, which is why testing is so important.