TWiV 654 TWiVering with Excitement

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 16 August 2020

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick. From MicrobeTV, this is TWiV, This Week in Virology, Episode 654, recorded on August 14, 2020. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York State, Daniel Griffin.

Daniel Griffin: Hello, everybody.

VR: Also from New York state, Chuck Knirsch.

Chuck Knirsch: Hi, Vincent, Daniel. Good to see you both.

DG: Let me go ahead with our updates. I know we have a lot of clinicians. Initially, it was the ProHEALTH New York but it has now become the ProHEALTH Riverside Tri-state Area clinician update as we’ve grown and merged. Let me start with my quotation. This week it’s actually going to be song lyrics. Trying to reach out to the younger crowd. This is the song, “Epiphany” from the album “Folklore” by Taylor Swift. I don’t know Vincent if you’re a fan or not. Chuck, you’ve got some teenagers so maybe you’re familiar with Taylor Swift.

CK: Sure.

DG: When I’m not doing this and seeing patients, I’m watching Dr. Who and listening to Taylor Swift just to give people some background. She actually wrote this song and it came out. It’s about the healthcare workers and the experience with COVID-19.

“Something med school did not cover, someone’s daughter, someone’s mother. Hold your hands through plastic now, doc, I think she’s crashing out, and some things you just can’t speak about. Only 20 minutes to sleep, but you dream of some epiphany, just one single glimpse of relief to make some sense of what you’ve seen.”

I like to put this up front because I just want to keep a human face on the pandemic. Sometimes I feel like people lose sight of that. That the tens of thousands of people that are affected, the death counts. Each one of those numbers is an individual and we’re not doing well. We hit our highest one-day death count since May this week with over 1,500 deaths in a single day.

Then there was some data out of the CDC, were looking from March to now, we’re seeing over 200,000 excess deaths based on this data. Some even say the actual number may be even higher than losing 200,000 Americans because I would say it takes time to die but it also takes time to count all the deaths in the country.

I want to actually applaud in this context here. The Houston Methodist Hospital, I don’t know if people saw this. When we were seeing many COVID cases here in New York, I have to say I was a little bit frustrated and I know the media was a bit frustrated and would reach out to me because it was really hard for them to enter the hospitals and really report and show people how bad it really was, how overwhelming the situation was.

I understand to some degree the hospitals didn’t want to look bad, they didn’t want to be the COVID hospital. I think because of that a lot of people still don’t have a grasp of the human tragedy that was here. This was an article called, Inside the Fight to Save Houston’s Most Vulnerable, it’s a New York Times article and they really did a great job of really capturing the human impact of this and bringing it home.

They actually went through several individuals. They talk about how it isn’t the young people at the gatherings who are maybe not following the rules. They talk about an aunt, a grandmother, a father, the delivery worker, and all the really hardworking people who are just trying to get through their day and end up getting exposed, end up suffering from the virus.

I’m actually perhaps a little optimistic that when people read stories like this and it makes the virus real and the danger understandable, that people start to appreciate why they’re being asked to make the sacrifices, and maybe making those sacrifices will become a little bit more acceptable because these, as I guess in the Taylor Swift song–

[alarm rings] I have an alarm that just went off there. That was my alarm to get ready for this show.

Now, I think as people look through this, they’ll see all those numbers, that’s someone’s daughter, that’s someone’s mother, this is a human being. Those aren’t just numbers. Thank you to the Houston Hospital for opening their doors and telling these stories. What I’ll say also is transmission was another preprint out there. I think everybody is obsessed with the aerosol-producing procedures and the possibility that this is an aerosolized.

This is a report called Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients, it’s a preprint, and they actually cultured the virus and showed CPE, so our TWiVlers will know, cytopathic effect from what they obtained from the air and the room of this patient. I think that changes what we’re still saying, we still say, I think when Anthony Fauci was on, he was very clear that the majority of transmission here is droplets, there is some contact when people touch a surface and maybe they touch their nose or face like Vincent’s doing. I’m just watching that as he infects himself with SARS-CoV-2 there.

VR: I’ve been home all day.

DG: There are certain circumstances where you can have aerosol. We know if there are particularly if there’s aerosol producing procedures. We also know that there is a big impact of transmission when people are indoors. Unfortunately, I feel like we’re losing our warm weather window to really get the numbers down in a lot of areas. As people come back indoors we’re going to have more transmission issues.

VR: May I say something about that study?

DG: Yes, please do.

VR: We have no idea if the amount of infectious virus in those aerosols was enough to infect anyone. We know a patient in the room who’s exhaling virus, there’s going to be some infectious virus in the air. What we do know is if you’re opposite someone for 15 minutes that’s when you’re likely to get infected because you’re constantly inhaling droplets. I’m not worried at all about a few aerosols with virus in them because we have no idea of transmitting by that route.

DG: I think that’s an excellent point because these preprints, these things end up out there, and then suddenly the media jumps on it and suddenly there is– there are certain things I think that we’ve repeatedly talked about, call it the misinfodemic.

VR: Yes, for sure.

DG: It’s really misinformation. It’s this fear that every day we find something new, and, “Oh, my gosh, it’s all wrong what we’ve been told.” It’s not all wrong. We’re millions of cases into this. It’s mainly droplets spread and there is a minority of situations where it might be spread other ways.

VR: I saw a headline in the Times about that article saying, this changes everything.

DG: It doesn’t.

VR: No, it doesn’t. Come on people.

DG: Remember, good news is not a headline. Bad news is the headline.

VR: That’s right. You’re absolutely right.

DG: Testing actually, I’m going to try to devout a lot of what we talk today about testing. I really think this is key. I was listening to the most recent TWiV. That’s what I also do when I’m not listening to Taylor Swift, watching Dr. Who, or taking care of patients. I listen to TWiV, which, hey, I’m going to recommend. Everyone, listen to TWiV. Just a little background because I know some things were thrown out there, CLIA-waived.

I wanted to give people a little bit of context and then actually, I’m going to say this could be a little bit of optimism. I know that my wife refers to me as a bucket of sunshine, not without a bit of sarcasm. There’s a little bit of sunshine in the bucket here today. When you get a COVID test, when you go in there and you get that swab, that beautiful brain biopsy where a Q-tip goes further than you knew your nose went back, where did the COVID test?

Well, currently, about half of these swabs are routed to hospital labs, to university labs, to public labs. The other half are sent to the 12 major commercial labs throughout our country such a Quest Labs that we’ve talked about. Now, there’s alternatives to sending off these samples to these licensed labs. These licensed labs are actually defined in the CLIA-waived, are defined by what’s called, well CLIA. What does that stand for? Clinical Laboratory Improvement Amendments.

Certain tests that we do, we talked about these molecular tests, I like the fact that everything is a molecule so what makes something a molecular test? The amplification type technology, the PCR, the isothermic, the nucleic acid amplification tests. These are considered moderate to high complexity tests. These have to go to actually certified labs that have been shown to have proficiency in doing that.

These labs actually have to have a CLIA certificate. They have to be inspected. They must meet the CLIA quality standards. There’s an alternative to this and I think that we’ve been on an ark pushing for this. There’s what I referred to CLIA waived tests and these are determined to be simple tests where there’s really a low risk of an incorrect result. There’s not a complexity here that it needs to be at one of these sophisticated lab settings. These CLIA waived tests include the point of care tests that we talked about quite a bit. Those can be performed in a CLIA waived lab or at an office, an urgent care site, or even at a mobile site with a mobile testing license.

These are all tests cleared by the FDA. Also, within here are the home use tests. The FDA is telling us which tests can be used, where, and what hoops need to be jumped through so that we have some reliability with regards to those. Now, if your testing location changes, for instance, you say, “Oh, we’re going to go out in this school or this business,” in a lot of times you’ve actually got to go out there. You’ve got to get a special mobile testing license. I’m going to talk a little bit about how ProHEALTH is addressing this because we, like I think everyone else, are looking at the day when everyone has access to I think, Vincent, you want to charge everyone a dollar.

I would like it to be free so because I think it’s a lot cheaper to have the virus gone than it is to keep dumping a trillion dollars to help the stock market go up. We actually went through like a whole thing this week talking to the Tri-state Area physicians, so the recommendations for how we do this and in the 50 urgent care centers in the Tri-state Area, I think you’ll like this Vincent, we are investing in point-of-care rapid testing, where we’ll be able to have results in less than 10 minutes at all our 50 sites. We’re buying multiple Abbot ID Now machines for our multiple sites.

We’re in negotiations with BD to get those rapid lateral flow tests. What we’re really trying to do is actually when people say, “Hey, I can’t go ahead and open up my school, my business with the testing as part of the program.” We’re saying, “Give us a call, we’ll make it happen.” When those $1 tests come out, that’s great, but those $1 tests are not here today and you’re planning on opening today so, let’s make this happen. Just to let people know the rapid getting a result within minutes, it’s here and it can happen. For anyone who says, “Oh, we just can’t make this happen.” There’s no excuse just to make that public.

CK: You’ll report the results, Daniel, the positives particularly, but also just to know what our percent positive trend because I think that information is useful to public health or department health.

DG: Yes, all this stuff is tied in, Chuck, with the department of health. I think this week, we actually in New York State, we got up to the point where we are doing over 80,000 tests a day. There were two responses. One was, “Oh, there’s resulting delays, we should test less.” Our response was, “We should fix the resulting delays, so let’s get that resulting delay down.” Just now we have it down to minutes in several places. The worst we’re seeing is 36 hours, 12, 36 hours is much, much better. That’s having a test. As Anthony Fauci was saying, if it’s eight days, if it’s 13 days as it is in certain states, that’s like not having a test.

Let’s all do this. Let’s make this happen. I think there could be a political will, there could be an economic will. This could be done, we are doing it, we’re making it happen. If you’re not making it happen, then figure out what’s in the way because we need testing. I’ll get back to testing. I won’t be able to leave it alone for the next little bit.

Masks, it wasn’t wonderful. There was an article that came out in science advances, Low-cost measurement of face mask efficiency for filtering expelled droplets during speech. I don’t know if everyone got a chance to see that.

VR: Yes, I did.

DG: It was painful. It started– I’m not happy with the gaiter shaming that resulted from this article. There were some things that were interesting in there, but I’m not sure the study carries as much weight. There were certain things that looked interesting: the N95s, the surgical mask, the cotton mask that a lot of people are wearing looked pretty good. It was an interesting article. Vincent, do you have a take on this at all?

VR: I think they measure droplets by laser. I’m not interested. I’m interested in which droplets have virus and what masks do and so in my opinion, this study is useless and should never have been published.

DG: Chuck?

CK: I’m a little worried about the study too because one of the authors was on, I forget what TV show I was watching late last night, and they were suggesting that large droplets could be converted into aerosols with a single ply gaiter. I really think that’s a bad message to be putting out and I’m glad to see our virologist is shaking his head because I agree that these things shouldn’t get published.

DG: It’s worrisome because once this gets published then everyone jumps on it and you see all these– I was seriously, you’re seeing in social media now, gaiter shaming, where people are being tagged with pictures, “I saw your kids wearing gaiters. According to the latest research, that makes it worse.” Somehow wearing a gaiter magnifies the amount of virus that comes out of your mouth. Hopefully, again, this is our countering the miasma of misinformation. Again, this doesn’t change everything.

VR: Wear masks.

DG: Yes, wear masks.

School opening plans. I was going to skip this, I was going to not talk about school reopening plans, but you can’t skip it. People say, “Really, you’re not going to talk about it?” I got in the group of infectious disease doctors that I work with, one of the questions that came up actually earlier today was, we have a lot of individuals who have children and they’re older in age, they have other medical problems. Maybe they have lung disease, heart disease, and they’re worried maybe they even have immune issues and they’re worried, if my kids go to school, what will happen to me? We’re seeing now plans in our area where testing is not part of the plan.

They’re just going to send the kids, much like Georgia, going to send off to school. They’re going to be together even in a school bus, for instance, they’re going to be together in a classroom, and then we know what happens. Schools, these are cruise ships on land and they’re going to spread the virus and they’re going to bring it home to these individuals. The individuals are now asking, what can we do as physicians to guide them with regard to the kids going back to school?

This, like many listeners, this impacts me very personally. According to the American Academy of Pediatrics, the change in child COVID-19 cases from beginning of July to beginning of August, over that period of time, we had a 90% increase in the number of cases in children in that four week period from the period before. Just to be straight, kids can catch COVID-19. There’s every reason to believe that kids can spread COVID-19.

What I worry about and my comment to this group was, opening your schools without a plan, without testing is basically the equivalent of saying, “Go out there and drive, but we’ve taken away your breaks, we’ve taken away your seatbelts and by the way, those people with comorbidities, we’re going to pack them in the front seat blindfolded, and we’re going to let the children take the steering wheel.” As we just saw the experience in Georgia, I was really, I guess, astounded by the different media takes. Some people said, “See, we picked up these positive cases, we shut the schools. We have a plan and it works.”

I was like, “I don’t consider that working, but okay. If you’re okay with lots of kids getting sick and then bringing it home to their parents, open your schools without testing.” As I started with, there are groups, I mentioned Quest, LabCorp, ProHEALTH. There’s a lot of people with the ability to test. Let’s work together. If we’re going to make this happen and I feel a certain pressure. My daughter, Elise, my middle daughter who won the sailing race, she told me, “Daddy, if they open the schools and you let me go, I will hate you.” No one wants to be hated by their child.

VR: Daniel, I don’t know if you saw this week at the time. It was an op-ed by a pediatrician who claimed that children don’t transmit and I just do not understand how she can say that when we know historically children drive pandemics, there’s no doubt about it. Every pandemic, school and children drives transmission. I just don’t understand why she is saying this.

DG: Every respiratory pit, I look at the school calendar and determine my vacations. I don’t take off when there’s a school break, I basically prepare that right after the school breaks is when I’m going to really be busy and I need to be around because whether it’s influenza or whatever respiratory virus when kids go to schools, it starts circulating and then when they go spend time with family, what do we teach them in kindergarten, we taught them to share. We teach them to share in school and they certainly do that with respiratory pathogens.

CK: It’s not just children. When office buildings open up, but they don’t plan to test and to use masks religiously, 100% of the time indoors. So I think it’s the congregation that is important. I think some of the immune changes with influenza, I don’t know if we can port that to SARS-2 yet, but I think, we’re thinking a little bit about that. Testing has to be part of the school. The universities they’re trying to open. I have been doing the test runs of having different sites around campus, but they’re also doing food to go, not sitting around the dining halls. School will look drastically different for those that are trying to open and hopefully, this will be successful, but it is an experiment right now.

DG: Yes. It’s an experiment with a high cost. Experimenting with the lives of our children and families. I like that you bring up also work because we also get questions about that. We’re in the Tri-state Area, the center of this Tri-state Area is Manhattan with these tall 50-story buildings. How do people get from the lobby up to their office? Elevators and in residential, they’ll do things where it’s like one person or one family in the elevator at a time. Just imagine trying to get to work in a city where there’s a limited number of elevators. By the time everyone goes in one at a time, it’s five o’clock, and the lobby is still full. We really need testing to be part of this so that we can open the economy and do these things safely.

The other is, I’m going to give people homework. This is a teaser for next time. This is backed by evidence-based medicine. Next time when we meet, as my prep, I’m going to go through for the clinicians, what have we learned so far at the different stages? Also, how have we learned it? There’s been a little bit back and forth here. Back on TWiV 606, which was released in the end of April, April 26, I discussed the different approaches that physicians might use when they’re selecting therapy for their patients. We talked about eminence, vehemence, eloquence, diffidence, nervousness, experience-based, and then finally, we got two evidence-based.

There was a New York Times article called The COVID Drug Wars That Pitted Doctor vs Doctor, published August 8, 2020. It’s actually a very long, detailed article and I thought it was really interesting. It described the conflicts around these issues at the Northwell Hospital, so a lot of these people I know personally. It’s not an easy read, but I think it’s an important topic as we continue to move forward. Here we are, maybe six months into the pandemic here in the New York area and we’re still limited in what we have as far as randomized control trials. I have to start asking people to listen to that TWiV, at least the first part, you can keep going if you really get hooked.

Look through this because in the next episode, I’m going to talk a little bit about what we know, and how we learn this in this paradigm. The long haulers, I just want to say a couple of things about this. One is, I was just on the phone earlier with a young woman and the loss of taste and sense of smell has an interesting clinical course, I’m going to say. This is actually quite upsetting to people where they lose their sense of taste and smell but then what happens is something comes back, this foul smell, this metallic smell or taste. Interesting enough, that looks like it’s a precursor to people getting better.

We’re starting to have enough experience now that I can say, “Okay, you’re now getting that metallic that feel,” this seems to be things coming back and it looks like then they’re going to get the taste and smell back. That’s a bit encouraging. It’s a little bit of sunshine. When you get that nasty smell and taste, that’s encouraging. The other I wanted to talk about, long haulers and children, there’s been a bunch of articles about this recently. Again, this is going to be reassuring. I was talking to Jay Berger, who is the chief of our pediatrics group. We have thousands and thousands of children that are under the care of the ProHEALTH Pediatric Department.

We are not really seeing much in the way of the long haul in the children. This is a rarity, fortunately, so children can get infected, children can transmit, they are less likely to get severely ill, and they are less likely to enter into the long haul, the tail phase of COVID.

I’m going to finish on that note. I’m going to thank everybody for continuing to help us support Floating Doctors, we switched our charity. Floating Doctors is the group that I work with down in Panama, that helps the indigenous people in the Northeast Archipelago. As I mentioned last time, they’ve been for years going out to all these little villages by boat and helping these people setting up mobile clinics.

They’re continuing to do that, but now due to COVID-19, there’s incredible challenges with food insecurity, and that people are literally starving. Help us raise money, go to parasiteswithoutborders.com and donate and we will double your donations. We’re hoping to get that up to $40,000 that we can donate to Floating Doctors, to help these really hard-hit individuals and continue to provide medical care.

VR: Very good. Daniel. I wanted to ask you, you had sent me a document about testing, do you want to put that on the show notes for today, which has your table, your COVID test table, RNA levels, infectivity, and so forth?

DG: Sure, let me do that. I’m going to send it to you again because I left a little thing out in the table. I guess for our listeners, we’ve had a lot of people ask about, “Hey, how do I get that table where Dr. Griffin talks about different viral loads and the sensitivity of different testing modalities?” It’s in there where we talk about different RNA copy number levels and really the point at which people become infectious as well as which tests can give you a positive result at different levels.

VR: Great. We get a lot of requests for that. All right. Also, both of you, Daniel and Chuck, what do you think of this mBio paper? Is it mBio? I thought it was. Yes, mBio came out this week, Effective of Convalescent Plasma on Mortality among Hospitalized Patients, is the first three months in this very large study. Which is not a controlled trial, right?

DG: We were part of this so I certainly had patients enroll. Just to give a little background, and I’ll let Chuck jump in as well so we go back and forth. What this was, was really a compassionate use type of protocol. You could just say, “Hey, we now have access to so many batches of this plasma,” and you would go through and just give it to a whole bunch of people. There were a bunch of issues with this, as far as the publication, so it was not in any way a randomized control trial. Then what they did is they went back through this. I actually found this publication, I’m going to use the word “offensive” in their discussion, they’re a little too happy patting themselves on the back, I think some shoulders got dislocated.

What they say in their discussion is, when they set this up, there were a bunch of randomized control trials out there where individuals could be enrolled by their physicians into either a placebo arm or a convalescent serum arm. Or instead, they could say, “You know what? I just want to give my patient convalescent serum because we all believe it’s true.” They offered the wonderful opportunity to just circumvent the randomized control trials and just give everyone convalescent plasma who may or may not need it. Then they show a couple of things in the study. They show that, boy, early on, people weren’t doing so well, and then as time went by the outcomes were somewhat better.

Then they proceed to say a couple of things, they said, “You know what? The earlier in the course of disease that people got the plasma, the better they did.” Oh, and by the way, as time went on, people were getting it earlier in the course of disease, whether they got convalescent plasma or not, then it happened early on. If you look at it back in March and early April, people were not doing well and you didn’t have a lot of access to convalescent serum so people would be sitting in the ICU for a month, they were not doing well, you didn’t expect him to do well, the plasma would show up, and they would get it.

By the end of the study, as we saw, the plasma had higher levels of IgG, people usually were not quite as sick, but we had better access so less sick individuals were getting it. They found out surprisingly, the way I interpret the data, the people that got the plasma earlier with higher IgG levels did better than patients that got the plasma early on back in April when people weren’t doing well. I really thought it was, in a sense, a terrible study, because it’s going to give support but what they really did was in a sense, they cut the heels out of people who are trying to do proper randomized control trials, and here we are in August and we still don’t really know whether convalescent serum works.

If anything, there is one randomized control trial out there that showed no benefit and there could be more if they hadn’t had this “compassionate use program.” I’m now going to step off the soapbox, I’m going to let you step on it, Chuck.

CK: This is a resource-intense procedure and not without risk and so we actually need to know whether it works. I look at it in terms of the weight of evidence. I would place this in the category of big data observational studies. Interesting, but is hypothesis-generating for the randomized controlled trial that must be done, so it would not alter my clinical practice as it’s clearly true. What you’re saying is well, but would have me design a randomized control trial? If this did undermine randomized controlled trials, that’s a shame. That just shouldn’t happen.

DG: Yes, Vincent, like if you look through the discussion, they pat themselves on the back, saying, “A lot of doctors would rather give what they think works than enroll their patients in a trial,” and we gave them that option. It’s sort of like, “Oh my.”

VR: From my view, patients got all other treatments in addition to the serum. It’s all over the place. If you look at the graphs, where they’re comparing recovery with doses, and so forth, all the error bars overlap. You could argue that they’re really all the same. Would this change what you do with patients, Daniel? Would you give them serum based on this?

DG: No, if anything, this was a huge dataset, many tens of thousands of patients, and they still couldn’t show anything significant even with all the flaws which would bias it toward showing something significant. If anything, I see it as more science that does not get me excited about convalescent plasma. If you need more than 10,000 patients in a study and you can’t show significance, I’m not really excited. Like they say 30% whatever reduction, but 30% if you take like 12% and move it down to 10%, the absolute numbers are very small.

VR: When you’re in the hospital, you’re beyond the virus stage. You have other issues that aren’t going to be mostly taken care of with antivirals like this. We see that with remdesivir. It has a modest effect because what you need is modulation of your immune system, et cetera. Okay.

CK: I think we’re going to have engineered antibodies that have been properly studied because they have to be studied. That would replace this anyway if it works.

VR: I’ll be surprised if that they have an effect because, again, hospitalized patients IV, I think is going to have a modest effect but we’ll see.

DG: Yes, I agree. I talked about earlier that UnitedHealth Group was trying to partner with organizations that make the monoclonal cocktails to give them to high-risk patients in urgent cares in that first week when they should work rather than waiting till the virus is mostly gone and you’re in this cytokine storm stage.

CK: Yes.

VR: Daniel, you want to do a couple of emails before we–?

DG: Certainly.

VR: Paul writes, “Our COO of our hospital system contracted COVID-19. It’s cytokine storm, multi-organ failure, respiratory failure, ventilatory support. He did receive convalescence here and this was early March. He recovered and was discharged. Now he has lymphoma. You’ve spoken how there’s some thought that the virus might continue to exist or hibernate in lymphocytes. EBV is known to cause Burkitt’s, many other viruses that can lead to malignancies. Question is, are you seeing an increase in lymphomas in COVID-19 patients who recover?”

DG: Yes, Paul, thank you for this email. You hit several interesting issues here. One is this question about people getting infected with COVID. I should say people get COVID-19, they get infected with SARS-CoV-2, and then there’s a whole question about when does the virus completely clear off from the system and is there some persistence or whatever we want to call it? I don’t want to use the word latency because there are no genes that would actually establish latency. I think Vincent probably, hopefully, you’ll echo that or not.

VR: I agree with it. How can we know?

DG: Latency is not the right word, but it may be some delayed clearance. One interesting case recently that really played into this and makes me a little worried, it was an individual who had had COVID-19 early on. They were a lung transplant patient. When they started to have issues with rejection, the medicines were increased so their immunosuppressive medicines were increased. When they did that, the person started to actually seem to get sick, looked like they had developed acute COVID, but we knew they had COVID back in March, so didn’t make any sense. Did a COVID PCR and it was positive.

They had been sick, they had had many negative tests because we did that before they were put on immunosuppression, and now they actually– I’m a little bit concerned about this whole concept of delayed clearance as we’ve seen in certain things like Zika, not that there’s any latency. I don’t know if it’s hibernating in lymphocytes, I certainly don’t know how exactly it’s persisting. That was a little concerning that when people have a drop in their immune function that maybe we’re seeing a controlled virus that’s not completely cleared and maybe potentially start to replicate again.

As far as lymphomas, this is actually an area that I care deeply about, hoping I can eventually get funding to get back to finish what I was working on before COVID-19. We saw a significant increase in lymphomas in patients with HIV, even patients that were well controlled that had undetectable viral loads, that had good levels of T cells. We know that with Burkitt lymphoma, there’s some chronic inflammation that we poorly understand.

I always feel like it’s hand waving when I say chronic inflammation, but some sort of immune activation that looks like it links certain infections to malignancies, particularly lymphomas. I don’t think we have enough time to really see this at a significant level during this pandemic. Time will tell. I haven’t seen it myself. I don’t know if there’s enough time to go by. This is definitely something I’m going to have my eye on. Do we see post-COVID complications that would fall into this category?

VR: All right. Bob wants to know if you have seen COVID-19 patients with POTS and if so, what can be done? What’s the prognosis?

DG: We’ve certainly seen people develop what might be POTS, what might be this Postural Orthostatic Tachycardia Syndrome. There was a Lancet Neurology article that came out, neurological complications– actually, there were a few patients in there that looked like they might fit these criteria where they develop COVID and then afterward they’re having issues when they try to stand, they have tachycardia, they have problems maintaining their blood pressure.

We don’t really know, but I would say early on, we’re seeing what looks like an autonomic hit. To give people a sense, we have our sympathetic and parasympathetic autonomic systems. When we stand up, this allows us to maintain our blood pressure. A lot of people after COVID in this tail phase seem like they’re having issues with hypotension, with we’ll say, autonomic dysfunction. I don’t know if they’re going to actually fall into a classic POT syndrome or not. I’m still hoping these people eventually get better. Yes, we’re starting to see some reports of this.

VR: Okay. Liz wants to know– she has two questions. “First, cytokine storm and the long haulers you’re seeing, is this unusual for a viral illness?”

DG: It isn’t, actually. I think we’ve talked about this on TWiV. A small percent of patients with other viral illnesses, we’ll use influenza as an example, have a tail. We know chikungunya is another classic, where people get this viral syndrome and three years, about 10% of people still have severe joint pain and fatigue. I actually have a friend, a physician in Seattle who three years is still having arthritis and fatigue, and issues. Unfortunately, certain viruses have this tail. It seems to be more common. It’s either more common with COVID or there’s just so many more cases that it’s really standing out for us.

VR: Okay. She has a reason for asking that because she has some freshmen who had similar symptoms, but didn’t have COVID. All right, secondly, “do you believe that the centers studying COVID long holders will be able to help them suffer the effects of other viruses in particular?”

DG: Yes, I hope, Liz, that we learn a lot. That’s one of my optimism, the silver lining of the pandemic. I feel like we will learn a tremendous amount. I think we already have learned a tremendous amount. I do have a lot of optimism that centers that are studying the COVID long haulers, will be able to help not only the COVID long haulers, but that we’re also going to be able to help other people that have post-viral effects of other viruses. Yes, I’m quite optimistic here.

VR: All right, one more.

DG: I was going to be free to go there. This reminded me of I think– Well, I thought it was a case, everyone can tell me if it’s a great case, but it was early on in the pandemic, so it was in March and I admitted a woman who had typhoid, enteric fever. One of the classic things about that is when you get typhoid with fever your heart rate stays low. I don’t know if people have noticed, but normally when you get a fever you get a rapid heart rate. When this woman was getting better, everything was great, it was very interesting story.

She had a cousin visiting from Pakistan who actually had multi-drug resistant typhoid and was spreading it to all the family members that we eventually figured it out after talking to her. When she came in, she initially had that high fever, she had the low heart rate. She was getting better, but she was getting better in a hospital that was starting to fill with COVID patients. She then developed a second fever, and then this time she had the high heart rate. Normally COVID fever– you have a high heart rate associated with the fever. You usually don’t have, at least early on, the slow heart rate when you’re having this fever.

VR: All right, last one from Amal who lives in Paris. He’s working, and he’s out and about. He takes precautions. He’s worried because he’s on anti-inflammatory drugs for shoulder tendinopathy, and he’s worried that he won’t get symptoms as a consequence, and he won’t know he’s infected. Should he be worried?

DG: Yes, it’s interesting. I was reading through this. I take public transportation and I also go to the gym every day. I’m trying to figure out the balance between going to the gym every day and exercising relative to the risk of going to the gym and exposing oneself to other people who are at the gym, breathing and doing all those things that people do.

What I will say is the anti-inflammatory drugs, early on there was sort of this big scare, there was a letter to Lancet, and it was basically saying, “We’re a little concerned about anti-inflammatory medications and COVID.” That has not panned out. If anything, it’s sort of a shame because the anti-inflammatory medicines like Aleve, like ibuprofen, like naproxen, really can have a tremendous impact on the symptoms.

When we finally realized it was okay to use these, you would say, “Well, why don’t you take an Aleve before bed, a naproxen before bed? Why don’t you take a few ibuprofen?” People were like, “Oh my gosh, I felt so much better.” We felt kind of terrible that we had deprived them of this relief because as we know, sometimes people have COVID not for just two weeks, but three weeks, but eight weeks. The fevers tend to come in the evening and at night. These nonsteroidal anti-inflammatory drugs can actually make a really big difference.

I’m not particularly concerned, Amal, I think it’s okay as far as those go. Yes, don’t touch your face, wash your hands, keep your physical distance, do all the other things. I don’t think that these nonsteroidal anti-inflammatory drugs are going to shut down your immune system.

VR: All right. That’s our weekly COVID-19 clinical report from Dr. Daniel Griffin. Thank you, Daniel.

DG: My pleasure.

VR: With commentary by Dr. Chuck Knirsch. Thanks, Chuck.

CK: Good being with you both.