In this week’s episode we speak with Monique Brouillette, from Scientific American who explains the varying stages a patient may go through after contracting the novel coronavirus — and the importance of receiving the proper treatment at each critical phase.


Jeffrey Freedman: Hello and welcome to the RP Health Cast by Rooney Partners. I am your host Jeffrey Freedman.

We are about ten months since this pandemic, and into studying the effects the novel coronavirus has on the human body. Now, scientists are learning more and more about the virus and how it affects the body each and every day. But a terrifying thing about the disease is that it appears to affect people very differently depending on their age, on their gender, and their genetic makeup.

Now, it is almost nine million Americans and forty-five million people globally affected by the virus, the scientists have been able to classify the disease into several different stages. And by doing, so they can begin to treat the symptoms and the underlying disease much better. And this is lowering the hospitalization rates and the mortality rates.

So last month, with the announcement of President Trump contracting the disease, these lessons learned along with new medical findings were certainly put to the test and the doctors and scientists at Walter Reed Medical Center were able to provide unprecedented treatment to the world’s most famous patient.

To talk to us today about the different stages of the disease and the potential different courses of treatment, we are very lucky to welcome Monique Brouillette. Monique is a freelance science journalist who covers Synthetic biology, Genetics, and Neuroscience. She currently writes bylines in many different Science publications including Scientific American, National Geographic Science, and WIRED, to name a few. And over the past year, she has written in-depth pieces about the coronavirus including most recently the President’s infection and his road to recovery.

Monique, thank you so much for joining us today.

Monique Brouillette: Sure. Thank you for having me. It is my pleasure.

Jeffrey: Now, you wrote a fantastic piece in Scientific American this month about the different stages of disease progression a coronavirus patient may go through. And you applied or you kind of superimpose these stages on the President’s infection. Now, I would like to start the discussion today, at first from a very high level. And if you could talk about those different stages that a patient may go through in terms of the disease journey. And can you talk to us about what they may be experiencing?

Monique: Yes, sure. Absolutely. So, just to begin, back in January when the pandemic started, doctors really did not know very much about how COVID-19 progressed. In the early days, if there is a new virus, doctors were scrambling to figure out what treatments to use. Of course, there was no test and treatment, and doctors were really just experimenting. Calling each other on the phone, comparing notes. I actually wrote another piece about this, too, in Scientific American. But now, it is October, we are ten months into this pandemic, and I think doctors have a much better understanding of how to treat their patients. And what is really emerging, is this idea that COVID-19 progresses in predictable stages, and these stages have important implications on how the disease is treated.

So, let us just start with the first phase, which is known as the viral phase. This typically happens in the first week, give or take, there is no hard-and-fast sort of deadlines. This is when the virus enters your body, starts replicating. Most people, of course, do not know exactly when this is happening, but about two to fourteen days later, they go on to get symptoms. And those symptoms are just kind of symptoms you would feel with any other virus, fever, aches and pains, cough. One thing with COVID that is unique is that people tend to lose their sense of smell and taste. And this is not like when you get a cold and you have a stuffy nose and you have congestion that gets in the way of tasting food, but it is actually just caused from the virus itself.

So, this is a very contagious part of the disease, and treatments during this phase are treatments that are targeted at the virus itself and fighting the virus. So, monoclonal antibody is for one. This is the ones that Trump received from Regeneron. These sort of, kind of act to mimic what your immune system would do if it were actually vaccinated. [Inaudible] artificial antibodies that shore up the virus and stop it from entering yourself.

Another treatment for the viral stage is the Remdesivir, which is an antiviral and stops the virus from replicating. This should also be given, I guess, during this phase of the disease. Now, many people will go on and get better after this phase. Many people would not even need these treatments. But if they do not get better, what tends to happen is they go into this second immune feed and that happens around the second week. Around seven to eight days, you will see people getting into this. And what they will see is that they are going to see their oxygen levels drop in this phase. They are going to have some difficulty breathing and this is really when most people head to the hospital. And it is there that they can go on to get that cytokine storm syndrome, which is this hyperactive response of the immune system. And your immune system releases all these chemicals called cytokine that signals the body it is under attack and they need to ramp up the production of other immune cells, macrophages, fever gets ramped up, inflammation happens. And in doing so, the immune system can actually start to cause harm to the body. This is when you see those telltale signs in the lungs that organ damage is happening there and sometimes this business is what causes the difficulty breathing. It can lead to a patient needing to get on a ventilator. There can also be damage to other organs like the kidneys and the heart.

Another treatment at this stage is geared towards the immune system. So that is when people will tend to get steroids. Steroids are going to tamp down the immune system. And you do not want to give steroids, usually, when patients are in that viral phase because in the viral feeds, you really want the immune system. They are kind of fighting off the virus. But in this phase where the immune system is the one doing the damage, that is when you will get steroids and things like that.

And so, after this phase, most doctors agree that there are two phases to COVID. There is a barrel phase and there is this inflammation, hyperinflammatory immune phase. But there are other things that happen with COVID that some doctors are calling separate phases and some of that has to do with some of the complications that arise from the inflammatory immune stage like blood clotting. The doctors I talked to said the one thing that is really unusual with COVID, I mean it can happen with other infectious diseases, but they are seeing a lot more with COVID is that people are getting blood clots. They are getting them in their veins. So they will have deep vein thrombosis in their legs or they are having pulmonary embolisms blocking the lungs and they are also getting arterial clotting which can cause stroke. And another thing that doctors are seeing are bacterial infections of the lungs, and even sepsis which is a bacterial infection of the blood. And that can happen as a result from this inflammatory immune phase.

And then the last phase of COVID is what people are now calling like that long tail or these people who are referred to as long haulers. And it is patients like one to three months out that is still just cannot seem to feel better. They are still having trouble breathing. They may still be tired. A lot of patients complain about brain fog, trouble sleeping. This is kind of the final phase of COVID.

Jeffrey: Right. And that does not necessarily have an end date.

Monique: Yes, I do not think so. I think we are still learning, [inaudible] ten months.

Jeffrey: So, all right. Let us start over a little bit and you mentioned in the first phase, in the viral replication phase. There is that exposure or incubation period and a person may not even know that they are sick. They do not have any symptoms. Could they still be contagious at this point? Or could they be contagious?

Monique: Yes. And actually, that is one of the biggest problems. I think with COVID is that patients, I have seen some studies suggesting they are the most contagious, maybe a day or two before they get symptoms. And I think a lot of people are attributing that to why this virus has been able to spread so well.

Jeffrey: Yes. So, using the word spread. I mean, we are hearing a lot about that with what happened to the President. What took place at the White House, it was called super spreader events. Now, can you explain what a super spreader event is, and could the President have gotten sick at one of these events?

Monique: Sure, yes. So, a super spreader event, this happens when one person infects a disproportionate number of people. I do not know if you have seen these statistics around COVID, they say that each person who is sick can infect like two to three people, but we know though that there are instances where they can infect many more. In fact in my hometown of Boston back in February, there was this infamous meeting at Biogen where all these executives were flown in from around the world, about two hundred people were there. Two days later, about a hundred people left with COVID. They went back to their respective places and spread it further. So, I think these events, now, we are kind of understanding these events are actually playing a big role in this pandemic. For example, there was this research out of Hong Kong showing that between ten and twenty percent of infected people are actually responsible for about eighty percent of the coronavirus has spread. So, did this happen with President Trump? Did this happen at the White House? Anthony Fauci said it did. So, I will agree with him. [Inaudible]

Jeffrey: I will always agree with Anthony Fauci.

Monique: For sure.

Jeffrey: So, you mentioned that most people head to the hospital after this, when things get so severe in terms of if they have trouble breathing or if these symptoms get more than a little annoying. And they are put on a whole regiment of, if it is pre-steroids, they are put on the Remdesivirs. It seemed like the President got everything all at once or at least that is what he was saying when he went to Walter Reed. Is that a normal course of treatment?

Monique: No. I do not think there was anything normal about the course of treatment from what I understand. So, I guess if we go through the timeline. Trump, officially Trump said he started feeling sick on Thursday night, which is when he got a COVID test. And then the next or early in the morning Friday, he tweeted that he had tested positive. At that point, I guess he was reported to have had congestion and a fever. And he was given a course of those monoclonal antibodies from Regeneron, which would have been appropriate for that phase, if he was in the viral phase. And then Friday, he went to Walter Reed, I believe it was on Friday. And I think there was just a lot of confusion about that because his doctors were saying he feels fine. He is at Walter Reed and we hear he gets dexamethasone. And he was also put on Remdesivir I believe, which would also be appropriate for the viral phase. But the [inaudible] doctors administered steroids is a bit confusing because as I said, steroids can actually be damaging to somebody in those early phases. You do not want to hurt your immune system’s ability to fight off that virus. And I have seen some explanations for that.

Some people have sort of postulated maybe because he got these antibodies. They just wanted to, they figured well his immune system has these artificial antibodies that will fight off the virus. Let us give them the steroid to make sure that just as a preventative. But then I heard what is more probably likely is that when he went to the hospital, maybe on that Friday, he was actually entering the immune phase. And so, maybe he was not, like his timeline, I guess he said he started getting symptoms Thursday, maybe that is true. People can get symptoms anywhere between two and fourteen days after they are infected. But I think what is becoming clear is he was probably entering that immune face because later we also found out, well, his oxygen levels dropped. He had some quote-unquote expected findings in his lungs and I am not sure anyone really knows and I am not sure anyone has gotten more clarification on that. But I think that is probably the likeliest explanation, which would explain why he got the steroids and it would actually mean that his doctors were just following the standard protocol.

Jeffrey: Okay. And you mentioned that immune overdrive phase and tied that with cytokine storms. Can you explain what exactly that does in a body? Like a cytokine storm, what are some things that may come of it?

Monique: Yes. So, the cytokine storm is basically your body is overreacting, releasing all these chemicals that say that ramp up inflammation, ramp up immune cells, ramp up fever. And it is really an overreaction and as I said, this can go on to cause organ damage. People are having heart issues, kidney issues. And then the biggest, I think with COVID again, it is like the biggest issue is this clotting. It is that people are, and even you hear, when I reported a story for Scientific American back in the spring, all these doctors were puzzled in New York during the surge. They said people would go home, they would get this cytokine phase, they would be in the hospital and then they would start to feel better and go home, and then come back a week later and suddenly they could not breathe well and they were having all these issues. And finally, they just pieced it together. Well, these people are experiencing blood clotting, and they are coming back in because they have pulmonary embolisms and lodged in their lungs now and they cannot breathe. And this, I believe, is when the
clotting starts is during that immune overdrive. It has something to do with that but inside of your blood vessels get hypercoagulable and you start getting these clots. And I really think that is one of the biggest issues with COVID and the biggest long-term effect of that cytokine storm.

Jeffrey: Right. And we still do not know enough about it or nearly enough about it. But that is different than what you mentioned before about the long haul, right? So, the long haulers, if you will, and I guess long haulers, those are people that have recovered from COVID-19, but they are still having recurring symptoms. They cannot get their health back to what it was pre-COVID-19. Are we treating, are they supposed to be getting treatment for these symptoms, or they just waiting it out?

Monique: Yes. I think they are. I think they are being seen as more outpatient sort of, in an outpatient way. People are, from what I hear from doctors, they are just treating them, like they are treating the symptoms. So, patients who have muscle and joint pain are getting non-steroidal anti-inflammatory drugs like Advil and such. People who are having insomnia, they are treating them with melatonin and antihistamines. People who have these long fevers, they just would not go away, they are just giving them Tylenol. I think increasing exercise, people who are really just, have lost that lung capacity, even, you know, they have started prescribing they work with physical therapists. And of course, for the emotional impact of all of this stuff, depression and anxiety, I think mental health referrals are up. So I really think it is just a treatment based, I am sorry, a symptom-based treatment strategy is what the doctors are doing.

I have talked to some doctors who say this is not so, I mean, this is unusual. We are seeing a lot of people with these problems, but they said it is not dissimilar to like chronic fatigue syndrome. These sort of long-term effects of maybe an infection, I am not sure what virus causes chronic fatigue syndrome, but they said there is some precedent for this. Yes. I do not think they have great answers and they are just kind of treating other symptoms with what we have.

Jeffrey: Okay. That is great. Thank you. That is very helpful. Now, as we are in the final days right now of the election cycle, thank goodness. But as you watch the President on the campaign trail now, he is talking about he is recovered, he is immune. A, could he be fully recovered by now? B, could he be immune? What does this mean in your eyes?

Monique: Yes. Well, I think he could be recovered. So, I know that his doctor, let us see. I am just looking at my timeline here. On October 10th, his doctor releases its memo and he says he is no longer infectious. And they did all these, I think they gave him a PCR test. And later, it was revealed that the PCR Ct value, and the Ct value of a PCR test is how many cycles it takes to detect the virus. And for somebody to be considered kind of recovered and non-infectious anymore, you have to have something like higher than 30s, a CT value of thirty-three. And I think he had something like thirty-four point five or something like that. So, he had cleared that viral face. He no longer had an infectious virus, so he was recovered in that way. Whether or not he is immune, I do not think anyone can say that for sure.

There are so many questions about, is anybody, what is the immunity to COVID-19? How long does it last? What does it look like? We are not even really sure [inaudible] immunity. Can we test people for antibodies? And if they do not have antibodies, which a lot of people who have had COVID-19 do not have antibodies, are we sure that, are they not immune, or did they be, they have another form of immunity through their T cells or some other sort of immune cells? So, we cannot really say for sure, I think, whether he is immune.

And I have also heard some people try and discussing whether or not the use of these monoclonal antibodies could have, which are basically synthetic antibodies that are kind of stand-ins for your own body’s antibody, maybe the people who get those will not actually develop their own antibodies to the virus. But again, I do not think there is anything definitely understood about this. But I think it is probably unlikely that he is fully immune.

Jeffrey: Okay. Still, too early to tell for any of this. It is incredible how much, how long 2020 has felt, but how short the time period is on how little we know about this.

Monique: Totally. Yes. I guess the last thing I would say is just that I think we have made a lot of progress and doctors have learned a lot just in the past ten months. I think in the beginning, treatments were being given may be out of sync with what is known about these phases and that may not have benefited patients, but now it seems like people are getting a better handle on it. And I mean, I am not optimistic[?], I think that is just going to improve and I think treatment is getting better for COVID-19. So, [inaudible] that is a positive thing.

Jeffrey: That is definitely a positive thing. And Monique, we have been talking about the disease as a standard thing, but there has been a lot of talk and a little bit of research done about the disease changing about mutations. And we hear about the flu every year, we need different flu shots because the flu mutates into a different virus. What do you hear about the coronavirus?

Monique: Yes. Well, this is a contentious issue, I will say. And I have written about this. So, there is this mutation in the coronavirus. It is called D614G mutation, and it is sort of quickly, I am not sure when it appeared, but now it appears that most viruses circulating have this mutation. And there has been a lot of fear that this mutation makes the virus more transmissible. And I think in the beginning, people wondered if it made it more sort of deadlier [inaudible] the disease out course.

So, yes, there has been a lot written about this and I think I will just let you know what I have learned from virologists. Viruses do not fundamentally change that easily. And although there has been some experimental evidence suggesting these viruses with this mutation, it may be easier for them to get into cells. I am not sure this is fully been verified by actual laboratory experiments that show that the virus can get into animals and transmits better. And even if it can transmit, just slightly better. I think many virologists, even if those experiments are done and we find, “Oh, well, this mutation may make it easier to transmit,” and that turns out to be true through very infectivity studies where they take the virus and they actually tested it an animal rather than in a cell culture or just through a PCR test. If this turns out to be true, I think most virologists that I have spoken to you said it is really nothing that is going to affect the pandemic in a drastic way, even really in that much of an impactful way. The thing about SARS could be, too, is that it Is already really, really good at transmitting. So, that is, I think, a reassuring thing from virologists. And there is, of course, no evidence that it changes the disease’s severity.

I do not know. In fact, some virologists would say, that I have spoken to, what happens with most viruses is that they actually lessen in severity, like the disease lessens their severity over time. And in some ways, are we seeing that with SARS could be, too? I have been hearing that cases of severe COVID are going down. And we do not know. I think that is still an unknown, why is it going down? Is it just younger people getting sick? I think the answers to that are unknown. But as far as the actual mutation goes, I think there is really no cause for alarm.

But it is something that comes up. This comes up in every outbreak and it is like something that people latch onto. It came up with Ebola, people were worried that it was mutating and getting worse. I have even talked to historians who are like, “Oh, yes.” People have said that about the pandemic of 1918 and they are like, it is so crazy because nobody even sequence viruses back then. So there is actually no evidence, but people were worried about it. So this just seems to come up every time there is a pandemic.

Jeffrey: And with that, I want to thank you for your time today and really appreciate every insight that you have given us.

Monique: Okay, great. Well, thank you so much. This was fun. It is my pleasure to be here.

Jeffrey: We hope you enjoyed this week’s podcast. If you have any questions comments, or a feature story suggestions, please reach out to us on social media. Thank you, and we hope you enjoyed the RP Health Cast.

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