COVID Context

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Resonance is a student-run podcast aimed at showcasing the science at Baylor through the eyes of young professionals. Each episode is written and recorded by students who have a passion for research and the medical community. Guests on the show include both clinical and basic science research faculty who are experts in their fields.

COVID19 is an illness caused by the Coronavirus SARS-Cov2, and this episode offers a summary of some of the information we have about this new virus from the scientific literature. The episode features medical students from Baylor College of Medicine, and contains general background about what the Coronaviruses are, epidemiology and symptoms of COVID19, and some of the current and future treatments.

COVID Context | Transcript

Roundtable Discussion

Brandon and Erik: And we're here.

Erik: Oh my goodness, we are here. This is the Baylor College of Medicine resonance podcast I am one of your hosts Erik Anderson.

Brandon: And another host, Brandon Garcia.

Jennifer: I'm Jennifer.

Karl: I'm Karl, I'm another writer.

Dan: I'm Dan, I'm just here.

Erik: Dan is also a writer.

Jennifer: You’re very important.

Erik: So this is a very, I guess, relevant episode that we decided to put out. Kind of on the fly, to do a quick: COVID-19 information, what is the newest in the literature…

Brandon: Coronavirus!

Erik: Yes, the coronavirus, to try to get it to your ears, and kind of point you in the direction if you want to learn more about it. So, we're gonna just kind of go through talking first about a little bit of background. What are the coronaviruses? And then a little bit of epidemiology, pathogenesis, and some of the current treatment options, and maybe some future ones that we'll be seeing.

Brandon: So yeah, basically we're all quarantined just like everyone else right now, can't do much, and we decided we wanted to talk about the Coronavirus and see what we could explain to you guys.

Erik: And before we start, I'd just like to mention something very important. We are medical students. We are not licensed medical personnel, and so everything that we are about to tell you is what we have learned from our research and from our own understanding of everything. But know that if you are feeling like you're having any symptoms, or any sort of like cough or fever, you should call your doctor.

Brandon: Yeah we’re medical students. We know a little bit more than maybe the public because we're in it, but that doesn't mean we should be your ultimate source of understanding what's going on. We definitely encourage you to go through, read the material, we will have it posted so that you can be able to see what it is that we read through, and realize that this is an ongoing situation. Meaning it's constantly changing. Information is going to change and update, and things are going to be different ten months from now than they are right this moment.

Erik: Yeah that's a good point. We're going to make it so that all of our references are available on the website. So, Jenni would you like to start?

Jennifer: Yeah I'm going to talk about the terminology, because Coronavirus, COVID, SARS, can be kind of confusing. But coronavirus is the most general term. So Coronaviruses are just a group of viruses that can cause respiratory disease in humans. And you might have heard of Severe Acute Respiratory Syndrome Coronavirus, or SARS coronavirus. Also called SARS, or also called SARS Cov1. That caused an outbreak in 2002. And then MERS Cov is another kind of Coronavirus that caused an outbreak in 2012. But now we're on to SARS Cov2, and that is what causes COVID19, but now people kind of use the terms interchangeably, so they might use COVID19 to just refer to the virus itself. Or they might just say Coronavirus. So that's what we're dealing with now^2,7.

Brandon: I actually remember as a kid…my family was really big on watching the news. I remember being like, what you said like 2002? So I was like 10 or 11, and I remember them talking about SARS and it being a big deal. So it kind feels like an instance of history repeating itself right now.

Karl: Yeah I think the big distinguishing factor was that the SARS-CoV1 outbreak, the 2002 outbreak, never really got too far outside of Asia, the original site. It spread to a few countries, it spread you know from mainland China to Hong Kong and so on and so forth, but it didn't go worldwide like we're seeing now.

Erik: Yeah and we'll talk a little bit about why that probably is, actually pretty soon.

Jennifer: Yeah so just a little bit about how this virus started from what we think. So patient zero seems to have come from a seafood market in Wuhan. There were 27 cases of a pretty bad viral pneumonia that were reported mostly from one specific market. And this was a market where they sold live poultry, and snakes, and bats. And other kinds of wildlife animals. And when they look at the DNA, or the RNA actually because this is an RNA virus^9,10. When they look at the genetic makeup of this Coronavirus it looks like it's a combination of a bat coronavirus, and it has some snake coronavirus elements as well. So it seems like the wrong bat met up with the wrong snake. Perhaps at this market³.

Erik: And this was in December of 2019 right? Which is how it got the 2019 designation, or the 19 designation.

Brandon: So this is some kind of bat snake thing?

Jennifer: Bat snake thing. But also there's no evidence that COVID19 infects cats or dogs. So for now don't be worried about, you know, your little fluffy companions.

Brandon: I just think it's interesting because from a viral epidemiology standpoint this happens every year with the flu. You know Flu seems to rearrange itself fairly frequently by this interaction between species. And when you have a virus that can jump between multiple species, and this seems to be another case of it. It’s just wrong virus at the wrong time hooking up in a weird kind of snake bat thing.

Karl: I think you are right Brandon, pointing out that with these new zoonotic pathogens—pathogens that have large components of their genetic code that come from animals—it's really like a perfect storm. Because our bodies aren't really used to it or familiar to it so we don't have good defenses for it. Plus, it's not well adapted to us, which means it might be a lot more toxic to us even though that's not really efficient for the transmission of the virus or the bacteria.

Brandon: I think this is important to talk about because it's a key thing to understand that this isn't like a man-made virus. It wasn't something created in the lab or it's not some kind of bioterrorism thing gone wrong. It's just the product of high population density both of animals and humans living together.

Erik: Yeah, and so to move on and talk a little bit about the epidemiology. One of the first big studies that came out February 24th was by the Chinese CDC and they did a study of about 44,000 confirmed COVID19 cases and found a case fatality of 2.3 percent. The case fatality is the number of deaths per confirmed cases^{4, 5, 6, 8}. So 2.3% would be 23 people in a thousand would die if they were infected. And then they also kind of stratified the population that it infected but we'll be talking about that a little bit more later. And very recent a study actually just came out that was looking at this percentage a little bit more closely, and kind of commenting that a lot of these numbers that you might see thrown around for other countries and places are actually difficult to really get a straight answer about. Because it's an ongoing situation. And so you might have a number of confirmed cases, but it takes two to three weeks to know what the outcome was, so that can kind of lead to some skewing. And then also if you're not testing all asymptomatic people, which we're definitely not, that's going to skew the numbers. So, with all that being said another team looked at a smaller cohort and found, trying to account for some of these variables, found that the case fatality rate was really more like 1.8^%7. Which is not to say that it's still not a serious thing, and just to give you some reference influenza has a case fatality of .0024%. So, the point being it's still serious and it's still an issue. One of the reasons why this is causing the pandemic that it is, is it's sort of at this sweet spot of infectious but also still being carried by a lot of asymptomatic people. Whereas SARS had a case fatality rate of like 14 to 15 percent, and that's what people think is why it wasn't able to spread as much because it was too deadly so it couldn't be maintained in the host. And I don't know if you want to talk about the R°? And kind of what that is?

Jennifer: Yeah, so R° is a concept in epidemiology that's supposed to estimate how many people will you give a virus, or you know disease, if you have it. So the R° for this virus is between 2 and 3.5, meaning that if one person is infected with COVID, they will give it to about two or three people on average.

Brandon: In contrast to that Measles is, if one person is infected they're probably gonna’ spread it to nine.

Jennifer: Yeah Measles is super contagious. And then I had the flu in here…

Brandon: I think the flu is like 3 or 5 somewhere in that range.

Jennifer: Really? I thought it was less than COVID, I thought it was 1.

Karl: Seasonal flu I think is maybe slightly over one so it's like really 1.1…1.3, I think typically. It depends on the strain.

Jennifer: Where’s our fact checker?

Brandon: Dan!

Karl: When we're vaccinated I think it's actually less than 1, that's why vaccines are so important. That's the important thing about R°, is that it’s modifiable by our behaviors and actions. Which is the whole point of the flatten the curve.

Jennifer: Yeah, and they think COVID might be a little more contagious than say the flu because there's a longer incubation time. So you could have it and not know for like a week or so, and you're just you know, living your life touching your eye and then touching things at the grocery store, etc., and spreading it to people without knowing it.

Erik: Yeah and I think that's probably a good transition into the pathogenesis to talk a little bit about how this is spread and a little bit more detail of the molecular physiology.

Karl: You mean it's time to get up close and personal with the Coronavirus?

Erik: One could say that!

Karl: So, Coronavirus is pretty interesting, there's actually a lot of different strains of Coronavirus that have kind of not very close relation to each other. This one obviously is relatively new to the human population. It is a very large single stranded positive sense RNA virus. It's about thirty kilobases, which for an RNA virus is actually on the larger side. The reason it’s called Coronavirus is because it has a crown like appearance when you look at it under the microscope. It basically has these little spikes that stick out of it, which some old-guy way back in the day thought looked like a crown. And then there's a Latin word for crown that's corona like, so they said Coronavirus. The spike proteins on the virus, there's actually two specific types S1 and S2¹¹. The S1 proteins are the ones that are used to usually grab on to your cells to help facilitate infection. And actually it's been talked about the receptor used by those cells is ACEII, which is Angiotensin Converting Enzyme Receptor II. Because there's multiple types of ACE receptors. And it's pretty interesting because that's also target for certain blood pressure medications and things, so that's a physiologically important receptor that it uses to dock on to the cells. There's also another peptide on there in the spikes called the S2 which helps for fusion of the virus into the cells. So, you have those two basic spikes that their whole point is to just get the virus into the cell. Once it's in the cell the virus does its thing, which basically means it hijacks your cells machinery to make a whole bunch of copies of itself, which then it can launch out into your body to spread the infection. Very complex pathogenic mechanism by this virus. It does seem to, more so than other Coronaviruses, really target the respiratory system. We're not sure why. And when we say the respiratory system, we really mean the lower respiratory system. So usually we divide into the upper respiratory system, which you can think of as things above the neck, you know in the neck and the head. And then the lower, which is in the chest, which is the lungs for the most part, that's the big thing for the lower respiratory system. And this is where Coronavirus really likes to attack. So yeah as far as transmission we have different classifications that are official classifications. Right now, we are certain that this is what's called droplet, it has droplet transmission. Which means relatively large droplets of water that come out when you cough, sneeze, spit, can carry the virus a decent distance, probably at least about six feet before falling to the ground. That's the whole social distancing keep six feet away. There is some discussion about whether or not it can stay in the air for longer, which would be considered more like airborne type transmission. That's an ongoing area of research.

Jennifer: But better to assume it's airborne and it not be airborne then assume it's not airborne and it is. So wear masks, you look cool.

Karl: It seems to cause major illness by triggering possibly an overactive immune response. There's a lot of intermediaries involved in this process, we think one important one is Interleukin 6, called IL-6. But there's a lot of other intermediaries. We can get something called a cytokine storm actually happening, where just a whole bunch of immunomodulatory chemicals are released into the body and it causes lots of issues. They haven't gotten a lot of chances yet to see what this thing looks like, what a person's lungs look like in an active infection. But it's interesting there was one case study where two infected patients were incidentally examined in China. They actually were people who went in for lobectomies, to have part of their lungs cut out because they had lung cancer, and they just happened to be infected. And they noticed and they got to look, and it did seem like in both of these patients there was a lot of edema in the lungs, which is basically swelling up. A lot of congestion of the blood vessels, once again is kind of like swelling or filling with fluid. There is what we call exudate filling up the lungs, which is a pretty common thing when you have a process called a pneumonia.

Erik: I was just thinking it's important for us to also make the disclaimer: We are not licensed medical professionals, just to reiterate. We are medical students. So everything that we're telling you right now is what we have found from, you know our literature search of the scientific literature, but if you're feeling any symptoms that you think are alarming then you should call your doctor.

Karl: That's a good point. We talked a little bit about how Coronavirus is spread and transmitted, and what it kind of does in a more scientific or detailed way in the body. But what are the general signs and symptoms that you kind of notice clinically when a person walks into a hospital? Or if you yourself were feeling ill, what should you be looking out for? So there is a wide spectrum of symptoms with this thing, that's one of the things that's tricky about it. As Erik has said, people can be asymptomatic and have no symptoms but still the virus. People can have really mild symptoms. People can have really bad symptoms like organ failure, respiratory failures. So wide spectrum. Of the people that are symptomatic we've noticed, seems like the consensus is starting to form that about 80 percent will have what we call mild symptoms. So these are people that are typically going to be okay if they just stay at home, isolate, make sure they don't spread the disease to other people, and just kind of treat this like a normal bout of the flu. So those people could have lots of symptoms, fever is the most consistent one. So most of people to get coronavirus have some form of fever, how severe the fever is varies but most people with symptoms will have a fever. Next most common symptom is a cough, dry cough, which means there's not usually that much sputum. You can also have things like fatigue, malaise, sinus congestion, or runny nose, a sore throat, body aches, very rarely diarrhea. So you'll kind of just have a lot of general flu-like symptoms with a big focus on cough and fever. That's about 80% of people. Then you have 15% of people, roughly, who are said to have severe illness. And looking around it seems like the agreement with severe illness, mostly what characterizes severe illness, is it does interfere with a person's ability to breathe in some way. So either people have difficulty breathing, or the oxygen saturation in their blood decreases, and that gets us to the 5% of people who have what's called critical illness. And critical illness is defined as people who have either respiratory failure, something called septic shock, or some sort of organ dysfunction or organ failure. And these people are very sick. A lot of these people their lungs just aren't working at all, and the only way we can really keep them going is to stick in something like a ventilator, which breathes for them essentially to try to keep them oxygenated. That's about 5% of people and that is really concerning because that requires a lot of medical equipment, a lot of staff, a lot of attention. And that's what we're really worried about with flattening the curve is trying to make it so fewer people get to that level of illness, which then won't strain our medical system as much. Does that make sense?

Brandon: Yeah.

Erik: Yeah.

Karl: So, usually for people they start the illness with mild symptoms, but for some patients they can start right away with breathing dysfunction. The patients that start right away with problems breathing tend to be people who are older or have pre-existing comorbidities, what we call them. So other conditions in addition to the virus.

Brandon: Like people who have heart problems, people who are supremely overweight, those kind of deals.

Karl: Yeah, yeah. It could be a variety of underlying conditions basically yeah. That's where you do hear about people with like cardiovascular issues or lung issues. For most people though, they have the mild symptoms. For a certain percentage of patients, after about one week, could be more or less, all the sudden they can have a rapid worsening of the illness where they start struggling to breathe. One of the most concerning signs I came across when I was reading they said was once the patient starts having difficulty breathing on their own in any way, or once their oxygen saturation starts to go down in any way, that's when you really need to keep an eye on them. Because that’s when they can take a massive turn for the worse, go into the critical illness state where they can't breathe on their own and that's when you really need to make sure you get on top of that and intubate or ventilate to keep them going alright. As far as making a diagnosis, a lot of this stuff is diagnosed just by doctors clinically, meaning they look at the pattern of symptoms and they say this was like what's going on. Then we confirm by testing for presence of the virus. There are a couple of imaging results that are indicative, but they're not super specific. So when they did CT scans of people's chests they did find signs consistent with pneumonia, because that's ultimately what this illness is, it’s basically a pneumonia. They also in some patients have found ground-glass opacities, which they think are indicative of once again inflammatory changes ongoing in the lung. But really, it's mostly something that we look at your clinical symptoms and then we make a diagnosis based on that. Confirm it with a test for the virus. I would say the big takeaway though is basically that people, once they get into the critical illness state, may require mechanical ventilation for a long time. Even sometimes there have been cases where people will prove for a little bit, and they'll take them off of ventilation, but then they'll deteriorate again and need to be re-ventilated. So it's looking like a lot of people may take two weeks or more on a vent to get them through it, which is why the shortage of vents is a big talking point we have in the modern medical picture. But hopefully we'll have enough of supplies and resources to get through this and hopefully we also have some exciting new treatments coming down the pipeline that will hope to mitigate the illness and make it so not as many people get into that rough of shape. What do you got to say about that Dan?

Daniel: Alright yeah so you've touched upon some of the mainstays of treatment and so we don't really have any real cure right now. There's a lot of medications in trials but right now the recommendation is mainly supportive care, symptom management, and a lot of that is going to be giving respiratory support —oxygen, positive pressure ventilation, and for the cases that do get worse, intubation, mechanical ventilation, and in some cases even something called ECMO, which is extracorporeal membrane oxygenation^17,18. And that's when you take the blood out of the body into a machine that could then exchange carbon dioxide and oxygen so it kind of bypasses the lungs, which in the most severe patients as you mentioned they're so waterlogged essentially that they can't really do anything. And you mentioned something else, which is that a lot of the damage being done to the lungs comes from something called a “cytokine storm” and the immune system response. So back when we had SARS when we had MERS, one way of thinking was, can we control the immune system—can we turn it down so the immune system isn’t damaging their own organs as much, and so they give people glucocorticoids. But after the fact, when they went back and analyzed the data they found out that this really wasn't helping and there was even an association that suggested this may even have been hurting the patients, which is why now with SARS-CoV2/COVID19 they're saying that the recommendation has been to not use glucocorticoids unless there's some other kind of comorbid condition like a COPD exacerbation.

Erik: Hmm, that’s interesting.

Daniel: Something else that's been said is don't use NSAIDs, and that comes from a few case reports pretty early on that said that maybe giving people NSAIDs to control their fevers might have been associated with worse outcomes. But there really has not been any clear data, no real trial showing one way or another whether NSAIDs are good or bad but that hasn't stopped some places from saying “yeah, no NSAIDs, let's be safe, let's stick to something like Tylenol/acetaminophen, which can break fevers and isn't an NSAID. And actually, something that's pretty interesting is in some places you can get Tylenol over the counter, and some places are sold out of it now. So everyone's stocking up on it.

Erik. Hmm. Can you speak to toilet-paper?

All: (laughter)

Erik: (laughing) No, so are there any interesting things on the horizon?

Daniel: Yeah, so you may have seen in the news that there's a lot of drugs entering trials right now and for those of you who are a bit more familiar with the intricacies of the pharma-industry, that might seem a bit quick. Like how can we go from, there's a new virus and then to where we’re trialing a cure in just one or two months? And the answer is this concept called “drug repurposing” or “drug repositioning”. And that's where we think, it's going to take a long time to develop something new, but what if we already have something that's maybe in development, maybe in trials, maybe even approved, and then and it has a mechanism that you know plausibly could work against this new illness, why don't we try that first, why don't we see if something we have in a little toolkit out of our arsenal can be used first. And that's where all these things that are being tested right now come from. They were developed previously for other diseases or other illnesses and they happen to have something about them, something about the mechanism, that says you know maybe we can use it for a COVID. And one of these mechanisms, one of these drugs, that's been getting a lot of press recently works through inhibition of the viral protease. So the viral protease is our enzymes that are made by the virus or encoded by the virus made by the hosts that are involved in processing viral proteins into a more usable form so they're in a central part of the virus's replication cycle. And this is the mechanism of an HIV drug combo, lopinavir-ritonavir, which was used back in the day to treat SARS and MERS, and was one of the first drugs that they tried in China to treat COVID19¹⁵. Unfortunately, this one's already failed a trial but it is still being tested in the WHO’s new trial, it's called SOLIDARITY. And you know what an acronym, you know props to whoever twisted you know ten words to be able to spell that out.

Jennifer: It’s almost as good as that DARTH VADER satellite.

All: (laughing)

Daniel: (laughing) But yeah, it's being tested in combination with other things like interferon-beta, which is something that your cells normally release in response to viral infection to help your cells, your immune system, fight off said viral infection. So, we'll see how those new trials go. And this is also the mechanism that this drug you may have heard of, or even used, called Tamiflu or to use the generic name, Oseltamivir, which has also been used by some hospitals and has also been trialed in some places. Another mechanism that we've got is inhibition of the viral polymerase, which is the viral enzyme that actually will engage with the viral RNA and to strategies here, we've got nucleotide analogs²⁰, which are incorporated into the assembling virus, and then through various means terminate replication, and we also have direct inhibitors of the RNA polymerase. Now the big name here is Remdesivir, which was originally made to treat Ebola virus, and since January it's been used in China, it's be used in Europe, it's been used in the US, in a few patients and in these case reports it's had supposedly some benefit and it's now being trialed, phase III trial in China. And it is also a major part of the SOLIDARITY trial. There's a lot of hope around that drug. Other things in that category, we've got Favipiravir, it's an anti-flu drug used in Asia. It's also had some claimed uses against COVID19 and the interesting thing about this one is that it's already had a very small clinical trial in China where they found that the Favipiravir was effective, but then it turns out that trial has a lot of questions about the way that it was conducted with the etiology, you know which patients were selected, the relevance of the population to the general population¹². So it's something we'll have to really wait for larger, more elegant trials, to really see. And probably the most talked about drug back in February was something called a Chloroquine, along with its close relative, Hydroxychloroquine. These are anti-malarial agents, but they also appear to have some activity against coronaviruses through a mechanism that's not quite fully understood, but it seems to have a lot of multi-access, you know, affect against viruses. They're saying that it might inhibit some of the pH-dependent steps in viral replication, it might prevent viral release through inhibition of autophagy and vesicle formation, it might interfere with surface receptors of the viral particle. And the major thing about Chloroquine is that it's one of the drugs that the China's National Health Commission, that their COVID report recommends. And both Chloroquine and Hydroxychloroquine are not part of the WHO SOLIDARITY trial. Interestingly there's a small French clinical trial that tested Hydroxychloroquine and they found that it's actually very effective in reducing the nasopharyngeal viral load¹⁴. And we mentioned that that's where the virus is going to concentrate and that's you're going to spread the viral droplets. But the viral load was reduced in these hospitalized COVID patients to a level where they were undetectable, so signs of strong potential there.

Karl: Maybe we should add a disclaimer here, these are all like early trials. Just because we think something like Hydroxychloroquine looks promising, you should still go to a doctor, discuss with a doctor, whether or not this is an appropriate therapy for you.

Erik: And I don't think anybody in the US is...

Karl: I think they're starting to try to roll out some trials in New York, nut I've just heard that anecdotally. But I have heard confirmed cases of people going out, seeing things on the shelf in the back of their garage that say “Chloroquine” on it and thinking I'm going to take some of this prophylactically. Do not do that. This is serious medication. You need to have a medical professional supervising you before you do anything like that.

Erik: Yeah, talk about side effects, isn’t it with the Chloroquines you get nightmares?

Daniel: These anti-malarial drugs have terrible side effects, and Hydroxychloroquine is actually the one using the US mainly because it's the less toxic version. Not non-toxic but less toxic. So those were some of the big guns right now, the ones getting the most press and attention but there's a few other strategies that are being considered one of them is using the blood serum, the plasma from recovered patients which should contain antibodies against the SARS-Cov2. And you give that serum to current patients and the idea is the antibodies will then attack the Cov2 in your current patients and help their immune system deal with it. That's the principle of passive immunization that is used a lot in infants and in the immunocompromised.

Erik: You might see “convalescent” is what it is called.

Daniel: Yeah, “convalescent serum” is the official term.

Erik: Yeah, the movie “Outbreak” really explains it quite well.

All: (laughing)

Jennifer: Yeah, that was a cute monkey.

Daniel: Hollywood just has so many of these movies about pandemics.

Karl: Yeah that was a cute monkey I can understand.

Jennifer: I’m glad it was immune.

Daniel: But there's also a large number of biotech companies that are kind of taken that one step further and saying what if we can make a better antibody, one that we can give to patients and kind of prophylactically give to these patients and prevent them from getting this illness. Kind of like a large-scale passive immunization program. And in terms of the timeline we could be seeing those being used around the end of the year. Whereas for active immunization, like what we should think of traditionally as vaccines, the optimistic timeline for them puts them out as being ready next year at the earliest¹⁹.

Karl: Any idea idea when we can expect a vaccine?

Daniel: Yeah, so the NIH has been doing a phase I trial on a possible vaccine that trial should be wrapping up at the end of April. Now a phase I trial is going to be mostly about safety. So is the vaccine safe to give to healthy people, and does that elicit an immune response in healthy people? So it's the very earliest stage and most of the drugs that I mentioned have done this already, like if they skip straight to phase II or phase III.

Karl: Because they're already proven safe because they're being used for other things

Daniel: Yeah, phase II is the kind of efficacy. You go to a small population and you say, does our drug actually do what it's advertised to do. And then phase III is your comparison and it says now, is your drug better than nothing? And it's only really after the phase III when groups like the FDA can say, I give you my approval to sell this drug to market. So some of the strategies that are worth mentioning, of only for the scientific interest, so Australia actually is piloting a massive trial of the BCG vaccine, now that's the childhood TB vaccine that the US doesn't use but many other nations around the world do use. And they’re trialing this in healthcare workers with the rationale that BCG may potentiate the immune response against other infectious diseases^13,16. And there's been some literature in the past showing that this effect might be real. So now they're trying to see if this can be used in any way against COVID19.

Erik: Do they think like heterologous immunity, like it’s ramping up the immune sysm?

Daniel: Something like that!

Karl: That’s a fancy word.

Erik: Thank you.

Daniel: And lastly, this is more related to symptom management than the antiviral effect, but it was also an IL-6 inhibitor out there called Tocilizumab, originally used for treating arthritis, but with IL-6 being an important mediator and the immune system being a cause of damage here they're hoping that using this IL-6 inhibitor can improve or at least ease the disease course for these patients²¹.

Erik: It's also high yield for the boards.

Daniel: Yeah so overall there's a lot of potential for something out of this massive, massive basket to be effective against SARS-CoV2 and COVID19.

Erik: And, do any of you want to talk about the other big thing that we hear about in terms of, I guess it's more prophylactic, of flattening the curve?

Jennifer: Social distancing. Which means...you know, concrete terms instead of buzzwords.

Karl: Hashtag flatten the curve.

Jennifer: Yeah, and like what does that mean.

Karl: Hashtag six feet apart.

Daniel: An ounce of prevention is better than a pound of cure. You don't want to get to the point where your options are supportive management and then hoping to get one of these drugs that hasn't been approved yet, basically an experimental drug treatment.

Jennifer: Yeah, so basically social distancing means, stay at home and only go out for essential things like groceries once a week or if you have to go to a pharmacy. But stay at home as much as you can, is what that means.

Danel: And one more important thing to remember is that some people are going to be asymptomatic, so you may have the illness but you just don’t know it but you can spread it to other people. And it may not be so harmless for other people.

Erik: For the reason that I think Karl mentioned, of if anything, because there are so many asymptomatic cases and mild cases, you might think that it’s going to be fine, but a lot of it is so that we don’t overburden the healthcare system.

Daniel: And especially for young people, there’s a persistent myth in some places that young people are not as vulnerable to this disease or are even protected against the disease and that’s really not true. Young people get the disease, young people die of the disease, there are a lot of young doctors in China, in the US, who have fallen victim to COVID19.

Erik: Yeah. Any other last thoughts?

Jennifer: I don’t think so.

Brandon: No.

Erik: We hope this has been informative. Again, we are medical students, we are not medical doctors, so if you have any symptoms, really just anything that you are concerned about, call your doctor because it’s better to be safe than sorry.

Karl: Yeah, it’s a tough time we’re going through but we just have to be smart and stay together, work together, look out for each other, and we’ll all get through it.

Erik: Alright, signing off.

Sources

Epidemiology:

Cohen, Maurie J. "Does the COVID-19 outbreak mark the onset of a sustainable consumption transition?." (2020): 1-3. https://www.tandfonline.com/doi/full/10.1080/15487733.2020.1740472.

Guarner, Jeannette. "Three emerging coronaviruses in two decades: the story of SARS, MERS, and now COVID-19." (2020): 420-421. https://academic.oup.com/ajcp/article/153/4/420/5735509.

Ji, Wei, et al. "Cross‐species transmission of the newly identified coronavirus 2019‐nCoV." Journal of Medical Virology 92.4 (2020): 433-440. https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmv.25682.

Mahase, Elisabeth. "Coronavirus: covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate." (2020). https://www.bmj.com/content/368/bmj.m641.long.

Ruan, Shigui. "Likelihood of survival of coronavirus disease 2019." The Lancet Infectious Diseases (2020). https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30257-7/fulltext#bib6.

Verity, Robert, et al. "Estimates of the severity of coronavirus disease 2019: a model-based analysis." The Lancet Infectious Diseases (2020). https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30243-7/fulltext.

Wang, Yixuan, et al. "Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures." Journal of medical virology (2020). https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25748.

Wu, Zunyou, and Jennifer M. McGoogan. "Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention." Jama (2020). https://jamanetwork.com/journals/jama/fullarticle/2762130.

Pathogenesis:

Cascella, Marco, et al. "Features, evaluation and treatment coronavirus (COVID-19)." StatPearls [Internet]. StatPearls Publishing, 2020. https://www.ncbi.nlm.nih.gov/books/NBK554776/#_NBK554776_pubdet_.

Rothan, Hussin A., and Siddappa N. Byrareddy. "The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak." Journal of Autoimmunity (2020): 102433. https://www.sciencedirect.com/science/article/pii/S0896841120300469.

Zhang, Yuan, et al. "A molecular docking model of SARS-CoV S1 protein in complex with its receptor, human ACE2." Computational biology and chemistry 29.3 (2005): 254-257. https://www.ncbi.nlm.nih.gov/pubmed/15979045.

Treatment:

WITHDRAWN: Cai, Qingxian, et al. "Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study." Engineering (2020). https://www.sciencedirect.com/science/article/pii/S2095809920300631.

Gautret, Philippe, et al. "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial." International Journal of Antimicrobial Agents (2020):105949. https://reader.elsevier.com/reader/sd/pii/S0924857920300996?token=1512E2C8FFF1138B0848EA96B7991D99458462F47E15EA7019E3CFE4EA9D18F0CC69979554EA33FFEF469F74BAFB0E5B.

Guo, Yan-Rong, et al. "The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status." Military Medical Research 7.1 (2020): 1-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068984/.

Higgins, Julian PT, et al. "Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review." bmj 355 (2016): i5170. https://www.bmj.com/content/355/bmj.i5170.

Holshue, Michelle L., et al. "First case of 2019 novel coronavirus in the United States." New England Journal of Medicine (2020). https://www.ncbi.nlm.nih.gov/pubmed/32004427/.

McIntosh, Kenneth. "Coronavirus disease 2019 (COVID-19)." UpToDate. Hirsch MS, Bloom A (Eds.). Accessed Mar 5 (2020). https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19.

Sandwalk. “Coronavirus Part III. Humankind firing back: Our molecular weaponry against it.” Sandwalk Bioventures. https://www.sandwalkbio.com/post/coronavirus-part-iii-humankind-firing-back-our-molecular-weaponry-against-it.

Sheahan, Timothy P., et al. "An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 and multiple endemic, epidemic and bat coronavirus." bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.03.19.997890v1.abstract.

Usdin, Steve. “Plotting a scientific path to counter COVID-19.” https://www.biocentury.com/article/304521/how-covid-19-response-is-stimulating-global-scientificcollaboration?fbclid=IwAR0Dr4jXTCRMA1CsGXMOkL43FLIDXHYMhTWu5pHS5_dXqfalzfnPdxo6gyo