COVID-19 Q and A: UNE’s Professor of Microbiology Discusses the Virus that Caused a Pandemic
For an expert’s view on the ongoing coronavirus pandemic, UNE’s Office of Communications recently consulted by phone with our very own professor microbiology, Meghan May, Ph.D. With degrees in microbiology, pathobiology, and bacteriology, May’s research primarily focuses on virulence – that is, a pathogen’s ability to infect a host – which is not only useful in determining how new diseases appear and where they come from but also in predicting what new disease might appear next – a practice known as pathogen forecasting. In fact, May was among the first people in the scientific community to publish (on January 1) the hypothesis that the mysterious new virus that first appeared in December of 2019 in Wuhan, China, was, in fact, likely a coronavirus.
In our conversation, May discussed, among other things, how the virus is transmitted, why the elderly may be so at-risk from COVID-19, and where things stand with possible treatments.
Many government officials have expressed the sentiment that they were completely blindsided by the novel coronavirus. Given that there is an entire scientific community that is dedicated to pathogen forecasting, was the emergence of this virus truly a total surprise?
There are a few papers in which people talk about the most likely zoonotic agents, excluding influenzas, to jump into humans, and coronaviruses and another family called henipaviruses are almost always right at the top of that conversation. And we’ve had several examples of both of those in the not too distant past. So this has been something that people in my line of work talk about with some degree of frequency -- that this is going to happen. So no, it's certainly not an unpredictable occurrence.
How are the emergences of these zoonotic viruses in humans predicted?
There are scientists whose entire line of research revolves around doing a lot of sampling of wildlife species that are known to be reservoirs of those particular types of virus families that pose the greatest risk for what we call spillover events [the transmission of zoonotic pathogens to the human population]. The idea is that if there's a lot of surveillance for these viruses that haven’t emerged in humans yet, then clever people would be able to predict which ones we could expect to be the most likely to actually emerge in cause studies in humans. And then on a translational level, it raises the question of whether we could even have a test all designed and ready or even a vaccine all designed and ready.
How has our understanding of coronavirus evolved over the past six weeks or so? What have we been able to learn from countries like China, South Korea, and Italy?
We don't know a ton about this virus’ basic biology. But there have been a lot of genome sequences that have come out, so we're able to look at its genetic diversity. We're able to tell who its closest relatives are in the coronavirus family. And we've been able to figure out what it targets on human cells, which is a molecule called ACE-2, which is the same protein that's targeted by SARS CoV-1 (the original SARS) and also MERS-CoV.
In terms of its epidemiology -- its disease process, its pathology, its transmission -- we have been able to kind of observe and learn a lot about it in real time. We have some knowledge of how long it lasts on different surfaces, the case fatality rate, and how it is spread. All those kinds of things seem kind of simple because we’ve been talking about them for a while now, but back in late December and early January, nobody knew any of that. So that’s been a big leap forward. One thing that is clear from studying the virus in other countries is that this is obviously transmitted person to person, but it's transmitted through something called aerosols and fomites, which is a little bit different than something being truly airborne.
Could you explain the difference between what it means to be truly airborne and what it means to be transmitted through aerosols and fomites, as is the case with this virus?
This virus can be coughed out by a person or sneezed out by a person, and it remains suspended in air for a certain amount of time. It looks like that amount of time is right around an hour, and then it can kind of fall down and land on doorknobs and surfaces and everything else, which another person could then touch and inadvertently put it in their own nose. Something that is truly, truly airborne creates a situation where you wouldn't have to be directly close to the person sneezing it out or you wouldn’t have to touch something that they sneezed near. It means a viable particle could truly float long distances in the air or float through something like the ventilation system on an airplane or something like that. This virus does not seem to be truly airborne in that way. It is transmitted by droplet aerosols. So that’s why social distancing and handwashing are being emphasized.
There seem to be many different theories as to why elderly peope are so vulnerable to COVID-19. Could you address this?
Everything that we're hearing now are educated guesses because we have not had a chance to really study what we would call the pathophysiology of this disease, which means, the actual step-by-step process by which it causes the damage to a cell that it does. We don't know that at all yet.
One of the things that, to me, is a very attractive hypothesis for why you might see these very exaggerated effects in older adults has to do with the immune system, but it's a little bit different than what we might think. To appreciate this hypothesis, you first have to wrap your mind around that fact that the damage that happens to you when you are sick with a viral infection, by and large, happens because of your own immune response. In an attempt to rapidly get rid of infectious agents, a lot of times you get these very massive responses that end up causing more damage in the act of trying to get rid of an offending agent. So you might use the analogy of a cancer patient getting chemotherapy. You're throwing this enormous drug at a patient to try to get rid of the cancer cells, and, in the meantime, you also get rid of a bunch of healthy cells. So you're causing a lot of damage to that person in an effort to make him or her better. Immune responses during an especially severe viral illness kind of operate on that same level. Now that being said, that might lead one to think that, well, since older people’s immune systems are a bit weaker, why wouldn't they then have a less severe response?
To understand that, we need to know that it's not necessarily that somebody's immune response, on a general level, just drops and becomes ineffective as they get older. It's the very specific and well-regulated adaptive immune system that is the one that weakens. That’s the immune system that helps you make very specific antibodies and very, very tailored reactions to certain pathogens. But the system that we call your innate immune system is still there and functioning, although it doesn't necessarily regulate itself quite as well as it did when you were younger. And so, according to this hypothesis, what you end up seeing is that the innate inflammatory side of your immune system still goes into action, is not quite as good at regulating itself as it once was, and then tries to compensate for this weaker adaptive side. And so it just ends up going bonkers, and it does more damage than it intends.
And then there's also the notion that older adults also have more comorbidities – diabetes or a circulatory problem or some other underlying health problem – so they're going to be at greater risk because of that as well.
While we all wait for the approval of a vaccine, what types of medicine or treatments are being studied as having some potential in fighting COVID-19?
There are a few thing that are being discussed. One is a compound called remdesivir by the company Gilead Sciences. It’s an antiviral compound that, at least in a lab, seems to slow the growth of the virus. It immediately went into some clinical trials and was given to some patients in China, and it seemed to work reasonably well. So that's promising. It’s a patented compound and could be produced right away. But the problem is that it was not approved for use in humans anywhere in the world and is still not, as I understand it. Why that is the case is not so clear. Is it because it was it just in a pipeline, and no one had gotten around to putting it through clinical trials yet? Or did toxicity studies in mice and rats go poorly? I don't know why it hadn't been tested, but nowhere in the world was this licensed for use. It did just get orphan drug status through the FDA, so that it could be distributed in the U.S. for compassionate care use, but again, no one is quite clear on what outcomes of that could be.
Another potential treatment that Trump has been discussing for the past few days is a drug called chloroquine and one of its derivatives, hydroxychloroquine as well as adjunct drug azithromycin. There was a very preliminary study done in France using a combination of hydroxychloroquine and azithromycin, but it's definitely not something that one should take to the bank as being the answer. For starters, it had only 40 people in it. Twenty of them received hydroxychloroquine, and the other 20 received “routine care.” But the “routine care” was at a completely different hospital in a different city, so we’re not sure what “routine care” even means. There were no age- and sex-match controls used in the study. And of the 20 patients who received hydroxychloroquine, just six of them also got azithromycin. So you’re talking about six people on planet Earth who have received this drug combination; it’s hardly definitive evidence.
There was another trial in China where they used just hydroxychloroquine, and that had up to a hundred people, but it was pulling information from 10 different hospitals where the treatment was given. And again, there was no age- or sex-match controls. The controls were from something like 20 different hospitals, and there was no continuity in what dose patients received or where they were in their disease process when they started getting treatment. So it's gently suggested that this might be helpful, but we are very far from being able to say that this a treatment that everyone should be using.
So, in addition to the fact that chloroquine and hydroxychloroquine haven’t been properly studied and found to be effective, there are four other major problems associated with their use, as I see it. First, chloroquine is a really toxic drug. It’s an unbelievably toxic drug. Hydroxychloroquine is better, but, still, it’s not a pleasant medication to take. You can give this to someone in their twenties who is at risk for having malaria, and they’ll deal with the side effects, but if you give this to somebody who's already in critical condition, you might hasten their demise. So that's problem number one: giving something with very bad side effects to people who are already critically ill.
Problem two: there are people who take that medication as indicated, and they need it. It's used to treat lupus patients, and it's not something we keep a stockpile of. So already all these doses are in short supply. And so we may create a situation where patients can't get their medicine that's working well for them. They will be in pain, and if lupus continues to advance, it causes heart damage, vessel damage and other problems.
Problem number three is that, this is an anti-malarial drug, and, as I mentioned, we have no national stockpile. So if we start buying it from other countries, who are we taking it away from? People who need it to treat or prevent malaria. And we would be taking it away in order to treat a disease when we don’t even have definitive evidence that it is actually doing anything to successfully treat.
The fourth problem is, I think, the less obvious one. All of these measures that we’ve taken in the past week and a half have been disruptive to everyone, but we’re doing it because we recognize this is how to slow down the spread of the disease. But when you’ve got a person in charge saying, “We’ve got this treatment; we’re sending it to hospitals; everything’s going to be fine,” are people really going to stay shut up in their homes? No. There's just a difference in risk assessment that people make when they think that they can just take the medicine and then there'll be fine. And so, I think there are real dangers in giving people false hope. Everybody wants to tell people that there's a cure and this will all be over soon. Everybody wants to say that, but we can't say that if it's not true. And the risk of saying that when it's not true and being wrong is really high.
There are a lot of myths around COVID-19 that people are finally becoming wise to. For example, it is becoming more widely known that yes, young people can get the disease and no, warm weather is not going to make the virus disappear. Are there any other myths, perhaps ones that have not been dealt with as extensively in the media, that you can dispel?
There is the belief that ibuprofen and ACE inhibitors could make the disease worse. That thinking is based on a kind of back-of-the-envelope kind of mapping that concludes that since these drugs cause your body to block a certain process that leads to inflammation and in so doing, cause your body to compensate by producing more of something called ACE2, which is the receptor that this virus binds onto, you will make yourself more susceptible to the infection, or will worsen the infection, if you take these drugs.
However, there doesn't seem to be any actual clinical evidence that taking ibuprofen and ACE inhibitors are having this effect. It's just somebody looking at it and saying, “I wonder if that would happen.” Certainly if you take ACE inhibitors to treat high pressure hypertension, you should not stop taking them unless your doctor tells you to. You have an actual risk with your hypertension if you don’t take them versus a theoretical risk if you do take them.
Read May’s January 1, 2020, Facebook post
Read May’s contributions to the coronavirus discussion in the news:
Portland Press Herald: Maine fitness clubs struggle to work out a coronavirus strategy
Portland Press Herald: Severely ill patients in Maine now receiving new drug to fight COVID-19