A Positive Look into the Future: An Interview with Dr. Jay Levy, Part II

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Cedar Hill in Central Park. Photo: JH.

For Part 1, click here.

JH: Do you consider this to be a once-in-a-100-year virus, or will we see more viruses of this ilk appear? One thing’s for certain — it’s exposed great weakness in our healthcare system, financial system, and otherwise. How do we prevent this little “germ” from taking over the world?!

Dr. Jay Levy.

Dr. Levy:  Let me give you this example. Think of polio. Now, in my day, we couldn’t go to swimming pools. Schools were limited. Because we were scared of polio. That affected up to 60,000 or more children per year in the United States. About 1 in 200 of these had paralysis, and of that number 5– 10% died. It was certainly a very severe epidemic that brought fear to the country.  Notably, the earliest help, as often it is today, was the prevention campaign of public health officials who instituted the building of sewers.  Then, the notable scientific  accomplishment occurred when the causative virus was isolated. And the final advancement was a vaccine that took many years. 

JH: And a vaccine for Covid-19? Where are we really with that?

Dr. Levy: It takes a long time to make and evaluate a vaccine. One step is to know what the immune system response is like in people who have remained without symptoms and yet are infected by COVID-19. The aim would be to mimic that immune response with a vaccine.  Once a potential vaccine has given that result in basic research studies, then it needs to be evaluated in individuals to see if it gives any harmful effects. 

This Phase I study may take one or two months particularly if the vaccine needs to be given more than once. Subsequently, one needs to test the vaccine in a small group of subjects in a community where the coronavirus is spreading. 

This Phase II study will determine if that vaccine reduces the disease and again is not harmful, giving no major symptoms. That can take several months. Finally, a large study (Phase III) would be begun to determine the effect of the vaccine when given to large populations. 

That Phase III trial could begin if early signs from the first two phases look good because of the harm of being infected with COVID-19. At the same time the government, in concert with companies, should be establishing facilities where large quantities of the potential vaccine could be made.

What we are doing now is prevention. Doing the best we can. Certainly, this virus will emerge again as we’ve seen with other respiratory viruses such as the flu.  Now it depends on what we call herd immunity, i.e. the number of people that need to have been exposed to the virus and are now immune to it.  They can prevent this corona virus from spreading.

The measles virus, for example, needs to find a new person every 2 weeks to replicate and pass on their progeny. So there are islands in the world in which measles has never been or no longer is seen. 

But if you take a person with measles into that island, it could be devastating. What I’m saying is the virus is now a human pathogen. It will circulate again unless  we have public health measures in place that reduce behavior that leads to infections by this virus. That needs to be done —until we get a vaccine. And we need to recognize this. 

DPC: What about herd immunity?

Dr. Levy: As I just mentioned, if enough people have been exposed to the virus or are prevented from this exposure the impact of the return of COVID-19 will be low.  Now, if you have a virus that spreads readily to  many people, your herd immunity to prevent it from spreading is going to require many people to have been exposed;  it’s about 90% for measles. With the flu, that’s somewhere in the neighborhood of 25% of the population. But with this virus, which spreads so easily, you’re going to need in the neighborhood of 60% of the population to have antibodies that prevent the infection on a regular basis. That’s why we have to assume until we have all of the testing, that we don’t have much herd immunity now — probably 1 to 2% in this country. 

In the meantime we need to do everything to prevent that virus from spreading. We can remain ahead of this goal because we are  wearing masks, washing our hands, and social distancing. 

JH: And what about the possibility of the virus mutating — can that happen with Covid-19?

Dr. Levy:  That is a great question, I’m always afraid to assume that nature/biology does follow some expectations.  COVID-19 is an RNA virus. RNA viruses mutate much more than DNA viruses.  In order to maintain their existence in nature, viruses may mutate sufficiently to be less disease-causing and more sensitive to the immune system.  Then there are more infected individuals carrying the virus but not succumbing to it. In this way the virus can remain an entity in nature.  

COVID-19 is a newly emerging pathogen, or one that newly found its way into humans. So it hasn’t mutated too much. But over a long time it may become less virulent or as we say, attenuated. Thus the viruses may mutate to the point where they don’t kill a person. It’s in their best interest. If they kill everybody, there’s no other hosts to go to, and that’s the end for the virus. Think of it as the survival of the fittest; the fittest in this situation would be a virus that’s not so deadly. There are examples of this biologic change particularly in the animal kingdom.

JH:  I see. So the goal of the virus isn’t to necessarily kill you, but rather to live long and prosper?

Dr. Levy: Yes, be fruitful and multiply. You may know the famous story of the rabbit population in Australia, when it got out of hand. probably in the 1950s. The government introduced myxomatosis into the country – the virus that kills rabbits. The virus killed off 99% of the rabbits in Australia. But the rabbits that survived had an immune response against this virus, and the virus in the rabbit no longer killed rabbits. 

It’s a natural selection. The animals that are going to survive are the ones that remain asymptomatic, and they pass it. Then that virus becomes more established in nature. 

JH: So if the virus then mutates like it should, that doesn’t mean the symptoms will be more severe.

Dr. Levy:  Exactly. But COVID-19 is doing a pretty good job now, isn’t it? When HIV emerged, people would ask me if this virus was going to be passed by the respiratory tract? At the time I said it’s doing a pretty good job now just being passed by blood and by genital fluids. It doesn’t need to change its transmission  route.  

At the time, we wondered if HIV would get worse, but there has not been any evidence that it has, but also there is no evidence that it has gotten attenuated. So there will be people asking that question while we can’t wait that long for the virus to replicate enough to become less virulent. And hopefully we will not see it get worse. 

DPC:  So basically under the circumstances now, with the virus the way it is, could we see another attack for everybody in a few months. Is that possible? 

Dr. Levy: Yes. That’s why we need to be totally prepared. We have today the scenario that says, okay, we were taken off guard; we shouldn’t have been taken off guard. And now we’re seeing the consequences — a lot of deaths. So that’s why we need to take this infection seriously, change our behaviors and importantly follow the recommendations of public health officials.

Why are they dying? They’re dying because, as I mentioned, the lungs, sometimes the kidneys, sometimes the heart are getting damaged. I think the heart gets directly infected by this virus and as has been seen with some respiratory viruses, the result is heart disease. 

So we have to be prepared. We aren’t.  Hopefully, our government is going to do that as you don’t allow people to just become relaxed until we know that the hospitals can take care of a large number of people who may need  intensive care, ventilators and/or dialysis for kidney disorder. When one says that they are flattening the curve, they are  lowering the rate of new infections. We may not be eliminating the infections but allowing the infections to occur in a staggered fashion. Then, hospitals are prepared to take on the severely ill patients. The death rate hopefully will be reduced. 

JH: And what about testing?

Dr. Levy: The important action is to test – to get to universal testing so that we know what the chances are that one comes in contact with the virus and how we can prevent that interaction. 

The only thing we’re doing now is trying to prevent that second wave from being as much a disaster as this is. If we pay attention to the most vulnerable we can keep people from coming in contact with someone who is infected and may cause severe illness in someone else. The key is, give us time. This is the first encounter with this virus and in this terrible unprepared situation. The next time around, we should be better prepared. 

JH: And what about the possibility of COVID patients getting reinfected with the virus. Can that happen?

Dr. Levy:  That’s not proven yet. We have no real evidence of that. There is a report from South Korea that they found the virus in people who have been free of the virus for months. For me, there are two reasons. One, which I think is the most likely, is that these detected viruses are dead viruses, killed by the immune system. Because detection was only the genetic sequence of the virus, whether that virus can give rise to an infection is the important question. 

And the other explanation, more importantly, could be that there is a reservoir in the body that continues to produce a virus but it is not causing any disease. That means there are certain reservoirs of the body where the virus is able to hide and avoid the immune system; so it continues to produce it for a while. That is going to be more of a challenge, but it can be handled. 

I really doubt this virus will come back and cause that person to have the symptoms that originally occurred. We have encountered this situation with some HIV-infected patients on effective anti-viral therapy. A small reservoir of virus replication was detected that was not being exposed to the anti-viral treatment.

JH:  I see. Which leads to the next question, and I realize we just don’t have the answers yet, but what about the potential of this virus causing permanent damage to the lungs and other vital organs of recovered Covid-19 patients?

Dr. Levy:  There’s a disease called ARDS, Acute Respiratory Disease Symptom, ARDS. The husband of a very close friend of mine about five years ago was in the hospital with this syndrome. No one knew what caused it but a virus is a usual suspect.  Now we know that COVID-19 can cause this kind of reaction in which the lung tissue is almost totally destroyed — either by the virus itself or, I think, with a coronavirus by a hyperactive immune system. The immune anti-viral response can come with such vigor that is causes great damage to the lungs.  The patient has to be on a respirator and that could be for several months to let the lungs recover.

So when I read of particularly older people who have died; their lungs aren’t as resistant, because the do not have the controls that our immune system has when we’re young. We have cells called T regulatory cells that make sure that we do not get autoimmune diseases such as lupus or rheumatoid arthritis because the immune system is hyperactive. These cells quiet down the immune system. As I mentioned before, this immune response can give rise to the disorders in the heart, kidneys and other tissues including possibly the brain — that could lead to strokes and strange behavior.

JH: It feels like a war between humans and the pathogen.

Dr. Levy:  It is a battle, absolutely. The good news is we know how we can limit it. For example, the number of people hospitalized in New York state has been slowly declining. There is going to be a solution, we know that. We know that from all we have learned from past epidemics, pandemics. 

There is a way to fight this battle while we wait for a vaccine, and there may be some treatment. But do the basics: wash your hands, social distance, wear a mask.  It is flattening the curve so medical care is available for those who are very sick and to help others to avoid symptoms. Eventually, we can all return to work. 

Transportation engineers will tell you how to handle safe behavior practices in metros, buses and other transportation services. Maybe we will have cars only come into the city at certain times or have employees work eight hour shifts, so there is less interaction. It’ll be tough, but we’ll get through it. And then if we get universal testing — that’s the big, big point — then we will have a a better idea whether there are pockets of this virus in certain areas that need very special attention. We will have a better idea if there are people who can go back to work with no problem. 

JH: Are you immune to it once you’ve had it?

Dr. Levy  That’s what I think. That is what monkeys infected with COVID-19 in the laboratory have shown. We should know that  answer as we start to allow people to circulate a little more. 

DPC: I’m going to ask you a personal question, I’m almost embarrassed to ask you, but anyway. 

Dr. Levy: No, go ahead.

DPC: On a Friday last year in early December, I woke up in the morning with a very strange sore throat, a horrendous chest cough with a lot of mucus, a headache, chills, along with a feeling that I felt like I could throw up —  I actually vomited a little, and my whole body ached. I couldn’t get out of bed, except to go to the bathroom — and I felt like I had a fever. I took my temperature several times during the day and it went to 99º but never higher. That was on a Friday, then Saturday.

When I woke up on Monday morning, I didn’t have a sore throat, and the cough had receded noticeably. And my body didn’t ache. But I stayed in bed most of the day. On Tuesday morning I felt better and went to the doctor who looked me over, and checked my heart and everything else, and said he really couldn’t find anything at all. 

Then on Christmas Eve, a friend of mine took me to dinner at 21, and she had exactly the same thing I had, same everything. In fact, she was apologizing for her cough. She didn’t cough actually, but she also had taken her temperature several times during the day because she felt like she had a fever. Could that possibly be some aspect of this?  

Dr. Levy: That was in December?

DPC:  Yeah, early December.

Dr. Levy: Alright, you’re talking to someone who also had exactly that array of symptoms  at the end of January. 

DPC: You did?

Dr. Levy:  Yes. I had chills. I thought I had food poisoning, in fact, I called the restaurant, but in two days I was over it completely. The fever was not very high. My wife, Sharon, and I knew of the recent infectious disease problem in China that could come to San Francisco, but we never really thought this was the coronavirus. 

I was sure it was food poisoning because I had been eating some seafood. Now what I’m going to say is when you can get tested for the antibody, have your friend get tested as well. Also, I’ll get tested. And if that’s the only thing we have for our symptoms, and we’re positive for COVID-19 antibodies, it might be worth a case report in a medical journal. 

DPC: So those very high mortality numbers that were being cited originally — was that a scare tactic in a sense to imply that if we didn’t enact these social distancing measures and stay at home orders, then hundred of thousands of  US citizens would die from it?

Dr. Levy: One was to scare people so that they know this is going to be high rate. And the other was not to expect people to do anything  giving this result. And it looks like as of this week we  are estimated to have well past 100,000 deaths soon. So, now is not the time to relax our attention to prevention.

Let’s put it this way — deaths are caused by the vulnerable getting sick, going to the hospital and not having the right care. If we’re taking care of that — and I don’t know if they can in all the States. But I’m hoping, as we all do, that we can control this pandemic in the United States. Science should lead the way.

The innovation of scientists in California, New York and the United States as well as throughout the world should discover a treatment for this virus before a vaccine. The finding of that treatment will begin by trying a variety of known drugs that are used for other diseases. These have the advantage of having been used safely already with humans. Remdesivir that worked on the related coronavirus, SARS, has some effect and given some hope, but we are looking for better drugs. 

By knowing the genetic sequence of the virus and knowing the protein products made by the virus, scientists and drug companies can start to try a variety of agents and compounds that can block formation of these proteins by the genes of the virus. Then, COVID-19 cannot replicate itself and will disappear. Let us have that great hope.

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