TWiV 656 See, it can be done!

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 23 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 656, recorded on August 21, 2020. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from Fort Lee, New Jersey, Dickson Despommier.

Dickson Despommier: Hello there, Vincent. How are you doing?

VR: Good afternoon. I’m well. It looks nice day out, isn’t it Dickson?

DD: It’s not so bad. It’s a little bit hazy, but the temperature is very, very nice. It’s, I would guess, 82 if I didn’t have a thermometer, and I don’t. The humidity should be around 42%, 43%, but I don’t have one of those either.

VR: You’re close. It’s 29c here in New York City.

DD: Look at that.

VR: Dickson, what do you mean a thermometer? Nobody carries thermometers.

DD: No, I just do this and then I stick it out the window.

VR: Also joining us from Madison, New Jersey, Brianne Barker.

Brianne Barker: Hi, it’s great to be here. It’s 84 here.

DD: 84, well, you’re in the heat bubble.

BB: I am in the heat bubble, but pretty similar. I think it’ll be a nice weekend.

VR: From Austin, Texas, Rich Condit.

Rich Condit: Hi, everybody. 96.

DD: It can’t be nice there.

RC: Well, it depends on your definition of nice. It’s 96 headed for 99. We got another week or so of 100-ish, and then I’m hoping maybe it’ll start to slack off a little. We’ll see. You get out early, everything’s fine.

DD: What’s happening to your COVID cases?

RC: Oh, it’s actually still trickling down just very slowly. I thought it was going to be actually leveled off where the most recent new seven-day moving average of hospital admissions is down 27. Baseline before the spike was about nine or 10.

DD: You’re talking about Austin or the state?

RC: Talking about Travis County. Travis County, what is it? Municipal statistical area or metropolitan physical area, it’s five counties. Actually, it’s more than Travis County, it’s five counties.

DD: What’s the whole state doing?

RC: Oh, the whole state? Man, you’re taxing me. Well, I can tell you–

DD: You got it in front of you.

VR: Let me finish introducing, okay?

DD: Okay, I’m sorry.

VR: Today is very special because normally, Daniel Griffin and I record his report on Thursday night, I splice it on, but today he’s with us from New York State. Daniel Griffin, welcome.

Daniel Griffin: Hello, everybody.

VR: Daniel, you get a day off and what do you do? You come to TWiV.

DD: Firemen’s holiday.

DG: That’s my wife’s expression. This reminds me of– I was with the family in Malawi, and the family was all excited we’re in Malawi and one morning, I’ve been there a day, I’ve got my suit and my bow tie on and my kid’s like, “Daddy, what are you doing?” I said, “I’m going to work. I have this opportunity to work in the central Malawi HIV center and I see 800 patients a day. I’m going to spend the day,” and they’re like, “Of course, daddy, your idea of vacation.”

DD: Do you have your pith helmet on also?

VR: I have to say that, Daniel, you may remember at the beginning of the pandemic, you would join us on TWiV from your car initially in the parking lot and then you joined us from inside and then you ended up switching it to Thursdays.

DG: It went through several iterations. First, I would be in the parking lot, and then there was a back stairwell, but then I realized it was a gap in the door, and then it just got to the point where I was like, “You know what,” record asynchronously and then patched it. It’s nice to see everyone. I watch TWiV.

VR: Here we are. We have two other guests today who are from Chattanooga, Tennessee, Lisa Smith, welcome to TWiV.

Lisa Smith: Thank you, Vincent. I’ve been dying to say this all week. It’s 70 degrees with rain.

VR: There you go.

LS: I blew it, too. I’ve been so pumped to say that. You can try, David.

VR: Also from Chattanooga, David Bruce, welcome.

David Bruce: Hey, everyone. It is 73 degrees here and we are Fahrenheit stuck in that. It is rainy. I like Fahrenheit. You guys argue this a lot. I like Fahrenheit because it’s a much broader scale. I don’t do Celsius, I do metric and everything else.

VR: Today we have an unusual situation, we have three PhDs and three MDs on TWiV. Look at that, we’re 50-50.

DG: Do I get to count in both because I have an MD and a PhD?

DD: He does.

BB: There’s seven of us.

VR: Yes, that’s right, there’s four PhDs and three MDs. Anyway, go ahead.

DG: I like to say, unlike Bill Nye the Science Guy, my PhD is real, it’s not armored.

VR: Yes, it is real.

DD: You have a functional PhD.

VR: David and Lisa have joined us and they’re going to talk about what they’ve been doing down there in Tennessee. First, we’re going to have our weekly COVID-19 report from Daniel Griffin.

DG: All right. Let’s start with our quotation. “There are a terrible lot of lies going about the world and the worst of it is that half of them are true.” That’s Winston Churchill. Let’s go through a couple things. I heard the CDC director, Robert Redfield issuing a stark message this week, said basically, “Follow recommended coronavirus measures or risk the worst fall in U.S. public health history.” It reminds me of the Christmas story where I think we’re being given a choice. We can follow all these measures or this is what we could expect. It’s in our hands.

Transmission and testing. I always try to leave this out but I just can’t because I always get questions. I try to take a week off but as my wife will tell you, that just doesn’t happen, I’m on the phone and conference calls, submitted a paper, and working on a second. A majority of Americans say that a negative test result should be required before returning back to work or school and many school boards are not really interested. I’ve actually been in dialogues here. Part of the issue is they say, “We don’t have the budget. We’re already strapped. Where’s this supposed to fit in?”

I’ve been in a lot of talks with parent-teacher associations, teachers associations, and really I’m just bringing up the option for, give your students, give your teachers and staff access. The school doesn’t have to pay for this, they don’t even have to orchestrate it, just coordinate because there’s a lot of programs out there.

According to the poll that I based this on, it was the Morning Consult where they say 73% of Americans say COVID-19 testing should be required for adults returning to work or students returning to school. Only 16% opposed mandated testing for the students, about 17% opposed it for employees. It’s similar. Most Americans have a sense. I think they’re drinking the flavored drink that testing is a way to make things open more safely.

This all really started actually, this, my front load part was here, was a ProHEALTH physician COVID update to discuss ProHEALTH’s program. A lot of this is a Tri-state ProHEALTH and Riverside required listening. Just to discuss, we have, I call it the “Tri-state COVID Testinator Program”. Some people who might catch that reference. ProHEALTH’s got a different name, they’re calling it the “Let’s Get Back Program”. By Tri-state, this is New York, New Jersey, and Connecticut.

This is all about trying to use testing to make a safe reopening of the economy and a safe reopening of schools possible. I like to point out that the end is– this is not a partisan issue. I think we all would like to be able to earn a living, and all of us, as much as I love my children, I would love them to have the opportunity to be out of the house more often than maybe will happen without this.

There are a couple of acts, there’s the Families First Coronavirus Response Act which passed on March 18 and there’s the CARES Act, that’s the Coronavirus Aid Relief and Economic Security Act, which really make COVID testing and associated services no cost to individual patients, and that’s supposed to be the issue. If you’re getting charged for any of this testing or these associated visits, speak up because that’s not supposed to be going on.

We’ve actually created a guidance for our Tri-state physicians on, how do you do testing? And which test, when? I’m going to cut to that and then back. What are the different testing options? I try to make this simplified. People have heard about PCR testing, and this is classic PCR, the original CDC FDA protocol. There’s also other ones that fall into the same hat. The Hologic Panther, which is a transcription-mediated amplification protocol which just allows for faster throughput. This is all basically your PCR-level testing sensitive down to a less than a thousand RNA copy number, really sensitive beyond the infectious period.

There’s testing delays, there’s resulting delays. We’ve got ours down in the New York area to about 24 hours or so. In a lot of parts of the country, it is more than eight days, it’s up to 13 days in certain places. Adding onto this are some of the isothermal amplification technologies such as Abbott ID NOW, which is a nicking enzyme or NEAR. It’s a nicking enzyme amplification reaction technology and some of the others. This cutoff is down to about 4,000 or 5,000 RNA copy number. These are a little quicker, some of them very quick, like the Abbott ID NOW, in minutes. Still again, your sensitivity is down, way past infectious levels.

We get into antigen testing, BD, Quidel, and nice news this week is that a U.K. company with LumiraDx, which got approval. These are still down to about 50,000 RNA copy number. These are actually pretty rapid. These are minutes. This is picking it up well below outside the infectious period. We’re actually looking at a re-analysis of the famous Seattle data with the anterior nares where you might be about three different CT cycles. Instead of 50,000 with the antigen, you might be a sensitivity of 50,000 if you really do the math on that.

Serology testing for prior infection. We all are in the school where it’s going to be 1 million, 3 million, maybe 5 million RNA copy numbers before people are in that infectious period. As far as our guidance on using the testing, because we’re rolling out in this, as I call it the Testinator Program, widespread access to rapid testing, but then of course we have backup with the PCR type testing as needed.

We suggest the Abbott ID NOW. We’re going to have hopefully multiple machines at all of our 50 Tri-state centers. We’re going to be coordinating with businesses and schools, getting results in less than 15 minutes. We estimate that this technology picks up greater than 99% of infectious cases. That’s pretty darn good for pulling infectious people out before they enter these spaces.

The rapid antigen test, this is actually interesting. BD was who we were contracting with, but the U.S. government has actually, for the moment, agreed or decided they will purchase all the BD rapid antigen strips. That’s a bit of an issue. I think it’s great that the government has jumped in and you can see someone is buying into that paradigm. For those of us readying ourselves to be using those, there’s going to be issues with access.

Those, we view as really great ways of picking up rapidly infectious cases. We were talking to one of the inner-city schools. A lot of people, if you have a turnaround, you may actually have trouble finding and connecting with that student or that individual who got tested. There’s a lot of advantages to this on-site rapid testing, whether it’s done at an urgent care center, at an office, at a mobile clinic, which can be set up.

We still have a lot of these nucleic acid amplification approaches, so in-house machines such as the one I mentioned, Hologic Panther or the commercial labs, Quest and Labcorp. We say that these are very sensitive for picking up infectious but probably overly-sensitive. It’s going to pick up individuals even past this infectious period. We’re basically saying as far as what tests should our providers be thinking about if someone comes in with what we think is acute disease, then we anticipate they’re going to have high levels of RNA. Any test is going to pick that person up.

If they have a negative rapid test, it seems highly unlikely to us that this is actually going to be a person whose symptoms are explained by the acute COVID. However, there’s the clinical judgment, the phases we talk about. If the person says, “I’ve been sick for 10 to 14 days,” and we’re really seeing a cytokine storm presentation, they may have low levels.

Those people are going to really be best served with the nucleic acid amplification testing. Putting this in line as we roll out our Testinator Program guidance for our clinicians.

Let me go back now to something I promised. I gave everyone homework. I don’t know if everyone here did their homework. I hope all our listeners did their homework. I see Dickson. Dickson never does his homework. That’s okay. I think we muted him, I hope.

DD: No, I give homework. I give homework, Daniel, I don’t take.

DG: I remember a lecture out in Minnesota and he was talking about tests. He’s like, “I don’t take tests, I give them.”

DD: Exactly.

DG: I have talked about a prior TWiV, Episode 606, where I talked about the different approaches for how we learn and how we decide what to recommend as physicians. I want to talk about this because there was an article that came out and a lot of people asked me about, “What did you think about this article, The COVID Wars That Set Doctor versus Doctor?”

It actually, just to give people context, who may or may not know me that well, run me a skit when I was a teaching attending. I was actually a teaching attending for one of the ICU doctors that I’m working with now. They basically do this skit where they make fun of your different teaching style, shall I say? The skit was about one of the attendings was grieving because Steve Jobs had died. He was in his office and he wouldn’t come out, and the other attending was like, “Oh, there are these pamphlets we have here.” He was explaining how important the pamphlets were. My role was I come on stage and say, “There’s no evidence to support the use of pamphlets in depression.”

It goes back a ways that I’ve always embraced the evidence-based guidance for us in the clinic. What I’m going to do now is I’m going to talk about what I think we know and the basis for that, so presentation in clinical course. I feel like this is solid ground.

We’ve seen millions of cases now, and we really have a good understanding of a first week being a viral phase, a second week being what a lot of us refer to as a cytokine storm phase. There’s, of course, discussions about, “Is that the right terminology?” But understanding that this is a time where we’re seeing significant immune pathology, a third week, which really overlaps where we’re starting to see the clotting or the hypercoagulable phase, this fourth week when we’re starting to see an increased risk of secondary infections, and then this tail phase, which we’re learning more and more about as time goes by.

A big thing is, how did we get here? How did we get that knowledge? You can actually go back to, I’m going to say, I’m going to suggest that this was really a productive, fruitful dialogue between people who are researching and publishing and people who are on the ground and seeing these things.

Back in the end of January, there was a Lancet publication, Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. This publication, I really thought was great. It started to report patients having fever, having cough, those with an identified exposure. For the first time, we start to hear cytokine storm, we start to hear D-dimer, procalcitonin, lymphopenia, IL-6. There’s even a mention of steroids and remdesivir.

This was good and bad because in a certain way, it gave a narrow perspective on the clinical presentation. A lot of people took away from this, “98% have fever, 76% have cough, the majority have an exposure, so those are the only people that we need to worry about,” this narrow lens, but by mid-February, we start to get a little bit more of a clinical experience. We start, I should say, realizing that the clinical presentation can be a bit broader.

The nice thing is, as the clinicians are seeing this and reporting this, you get an article that comes out of Wuhan, China. It’s a retrospective cohort study also published in The Lancet, Clinical Course and Risk Factors for Mortality of Adult in Patients with COVID-19 in Wuhan, China. This for me was the beginning of where we start to see the phases that we now talk about. You see the first week of fever, cough, malaise, generalized viral symptoms. The second week, you see the immunopathology, and then you actually even see and hear a discussion early on about secondary infections.

Buried in here actually, it doesn’t get a lot of attention at the time, but they basically say 50% of the non-survivors have clotting issues. You’re again hearing about lymphopenia, IL-6, D-dimer, procalcitonin, ferritin, and other inflammatory biomarkers. We’re actually starting to see, if you look in here and among clinicians, use of steroids despite, to be honest, WHO recommendations against this. This is nice. We’re starting to get a nice dialogue. We’ll talk about the not-so-nice stuff going on behind the scenes but I think this is nice.

We’re also getting data on the viral dynamics. I remember Steve Goff sharing with me the publication in The New England Journal of Medicine, SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. This came out on March 19. This really started to go along with the idea that a lot of us were discussing, which I think will later be fruitful, that the viral replication is starting early and by the time we’re seeing that cytokine storm, that immunopathology phase, the viral levels have really dropped by then, really to barely detectable, perhaps below infectious levels.

Actually, right about this time, Christian Josten’s publication, Virological Assessment of Hospitalized Patients with COVID-2019. That really suggested support for the concept of, phase one is viral symptoms, and then phase two is more of an immunological response. I have to say that it was really critical for clinicians to have these publications to refer to, to have their ideas refined by, but at this point, we start having the early skirmishes in the COVID wars. These were not clinician-researcher skirmishes; these were clinician-clinician skirmishes.

There were certain clinicians that had ideas about who should be tested and were, I’ll say, employees of large decision-makers that they were controlling those tests. There were also clinicians that had certain ideas on how patients should be treated. You actually started having some conflicts between clinicians saying,” I really am concerned that my patient has COVID,” but a limited number of tests. These gatekeepers were in this really not great situation of saying to their colleagues, their friends, “I’m sorry, we only have two tests per hospital, you’re not going to get one of those two tests for this patient. I’m going to allocate it to a couple others.”

That starts a little bit of a conflict in us and them. Us, who are looking at our patient one-on-one and advocating and then other people saying, “It’s a public health crisis here, we don’t have a test for everyone.” At the same time as this is happening, those of us who are seeing hundreds of cases in the outpatient setting and the urgent cares, we’re seeing that full spectrum of cases and really saying, “We need more testing,” where a lot of the ‘test gatekeepers’ are siloed in hospitals and they’re only seeing critically ill, very sick. They’re not seeing, I think, the full spectrum.

We then move into another conflict, and, again, this is not so much researchers quite yet, but people are starting to see the clotting complications in their patients and starting to ask questions. A nice story was captured in the Scientific American about this where I was actually on one of the medical awards with a bunch of the hospitalists. I still remember the story where they basically were saying, “We are seeing a lot of patients. We think they’re all having clots. We think they’re all having pulmonary emboli. It’s really hard to get these people scanned because the radiologists, they don’t want to die, they don’t want to get COVID, they don’t want us to send all these patients down for these angiogram studies, and actually coordinating where we send eight of them down and seven of the eight have massive pulmonary emboli.”

I remember the conversation happening, “What do you guys do? What? Are we going to put everyone on blood thinners?” They were like, “We should talk about that.” This was starting to create a very interesting dynamic where you were seeing things that we felt we knew how to treat from other diseases but yet you’re starting to get the question of, “We need to study these things.” At least I’ll say there was a nice dialogue between the clinicians and the other clinicians and the researchers and the people publishing that I think really helped us define the phases. I feel good about that.

Now I’m going to get to the second part. I don’t feel so good about this. The reason I put this in this initial physician part of TWiV is really the physicians and the researchers, I’m going to suggest if we work together, we can have a more productive next few months of this pandemic. I think we all would agree or there’s a lot of suggestion that COVID-19 patient care has rapidly improved. I think that if a COVID-19 patient is admitted now, their chances of survival are much greater than a person admitted in March, but this is interesting, why? Because we don’t have a lot of randomized controlled trials.

We went into this and I went into this with the idea that we will have better patient outcomes when we have those randomized control trials to guide us. What are we doing now? What are we basing it on as far as therapeutic? Mechanical ventilation, we moved from intubate early to avoiding intubation if possible.

A challenge in the early days was we had a very limited understanding of this disease. One of the first things we observed was that when we did intubate a patient, put them on mechanical ventilation, they seemed to get acutely worse. We had limited resources, and you also can’t intubate everyone simultaneously. We’d have one patient that we would say, “Let’s intubate this individual,” and we would do so, and then suddenly their support requirements would shoot up, their inflammatory markers would acutely rise. The person, maybe next to them that we just hadn’t gotten to intubate yet, would actually putter along, maybe stabilize, and maybe not intubate.

As we noticed from some of our publications early on, the people that got intubated, it was a minority of those people that ever ended up making it out of the hospital. There weren’t a lot of randomized control trials and actually there still aren’t randomized control trials helping us. There was a cohort study, Feasibility and physiological effects of prone positioning. We’ve talked a lot about prone positioning, putting people on their belly, not compelling in the literature that this is making a huge difference.

Institutional guidelines were put early on where they said, “You’ve got to intubate these people early because if you don’t there’s going to be huge exposure risks,” but then you had those of us at the bedside who would see this individual and we would care just as much about them as they might be our daughter, our mother. We would say we want to now avoid intubations. We’re really concerned about the harms. There was a bit of a back and forth here.

I will say we’ve moved in a direction here but we did not really get the randomized control trials and I’m not sure how we would get them. This is that parachute analogy people talk about. It seems to us very obvious that delaying intubation resulted in improved outcomes. Again, it’s going to be hard to get anyone to do trials where you take half your people in early intubate old standards and then you take the other half, use new standards. I think we just moved in this direction without randomized controlled trials.

The next I’ll hit on is anti-viral therapy, and I call this from the kitchen sink to just remdesivir. This was honestly a very difficult time. I know I’ve shared some of these experiences on past TWiV episodes, but there was really a significant change honestly in how bedside decisions were being made. In the old approach, your physician would look at the available options, maybe they would discuss with consultants, then the decision would be made.

There were committees at a lot of institutions that were not just producing guidelines, but really enforcing order sets. You would see order sets that were really just a bunch of clicks. A committee would decide that everyone should be on azithromycin and HCQ and vitamin C and thiamine, et cetera, basically, an order set would come up.

This was created by a committee. I could never find out who exactly was on the committee when I would ask, but it really made it very easy for people coming in to click, click, click, click down the list and your patient was now on the kitchen sink. If, let’s say, a prescriber had the audacity to start steroids, these committees actually had individuals who would go and discontinue the steroids. It was a very, very interesting time.

There was a bit of an issue, too, because you had people early on, and I think we saw a lot of these therapeutics playing out in the press, where people believed very strongly that they knew what was best for their patient. Now, the challenge was one week they felt very strongly that every one of their patient needed to get hydroxychloroquine and if it wasn’t given then it was unethical, and then they quickly moved to, “No one should get HCQ,” because getting it was unethical.

From one week to the next when you were trying to do randomized control trials, and I know sometimes I get accused of being part of the deep state or being partisan, but whatever side this comes out on, I actually set up two randomized control trials. When I set them up there was this huge input, “We’ve got to find out if this works. This could be a game-changer.” Once the trials were set up, either people didn’t want to enroll in the trial because they were sure HCQ worked so they’d want to be in my trial or they were sure HCQ was going to kill you and they didn’t want to be in the trial, and they didn’t want their patients in the trial.

This actually created a real impediment to getting people in randomized controlled trials. At the end of this, what do we have? We did end up with the randomized control trial supporting remdisivir but no statistically significant mortality benefit. It looked like in a certain group of patients there was a shortening of the hospital stay as a limited window, maybe it does a little bit. This was a trial with over a thousand patients. I had a fellow graduate student when I was getting my PhD who basically said, “If I need a statistician to tell me something works, I would like something a little bit better.”

We have remdesivir. Let’s go on to immune modulation during the cytokine storm. Here, from, “Never use steroids,” to using them for patients requiring oxygen or ventilatory support as the standard of care in most settings. This was interesting, and this was covered a bit in the Times article, but there really were a lot of conflicts here, and I mentioned the pharmacy gatekeepers, where early on if you put your patients on steroids at certain hospitals, those steroids would be discontinued by someone who felt that the patient should not be on those steroids.

You actually had physicians at the bedside thinking they were seeing a dramatic impact of steroids, probably true we now realize looking back. But then when they would rotate to a different hospital, they would see their orders discontinued or, as we see in theNew York Times article, they might be berated by a physician who would say, “You’re putting your patients on steroids. You’re killing your patients. What are you thinking?”

There actually were shouting matches, physician against physician rather than, I should say, discussions. Even when we ended up with the randomized controlled trial, the recovery trial, as we see in the Times article, you happen to have people saying, “Well, that’s just one well-controlled randomized controlled trial run by the leaders in the world, but another one might come out showing something different. I’m not sure we should all jump on that.” That, I think, left a lot of people frustrated. They said, “We finally actually got a randomized controlled trial. You said that’s what we needed to have and now you’re telling us that’s still not enough.”

Immune modulation. Here we are six months later, and as we’ve talked about in prior TWiVs, we still don’t know the role of a lot of other immune modulations now that steroids are becoming a background therapy, what the other therapeutics show in that background.

Now, I’m going to jump to anticoagulation. Here we also moved from one extreme to another from, “Never use anticoagulation,” to increasing use and increasing use of full dose anticoagulation. That has become the standard. Someone comes in early, they get remdesivir, they meet the right criteria. If they require oxygen or a ventilator, they might be on steroids.

Anticoagulation, universally, the guidelines now and the practices are putting people on anticoagulation, but I have to say, this again is this horrible parachute dilemma in many physicians’ minds. A lot of them feel like because they saw so many clotting complications, if they don’t put their patients on anticoagulation, putting them on nothing would be unethical. You’d be withholding anticoagulation, so to speak.

This is actually where there was a lot, I have to say, of conflict that occurred. The steroids, there certainly was a lot of conflict there. Anticoagulation, there was a lot of conflict. I’ll quote a couple of my colleagues. These are strong words at Columbia, but this was an ID doc at Columbia who said, “There seems to be a bit of bad behavior among the researchers.”

I have another out at one of the community hospitals who was speaking about one of the researchers, and this for him, who only says nice things about other individuals, who said, “He is not a very nice man.”

I’ll say that the researchers who quoted the New York Times article had slightly stronger criticisms for the clinicians. I think ‘witchcraft’ was a word that was used at certain times. The tough thing here is we think the patients are doing better, we do think that the incidence of thromboembolic complications is lower, but is this due to delayed intubation? Is this due to steroids? Is this due to less of those kitchen sinks therapeutics? Is it due to a lower census, a lower age group, less ill patients?

Here we are, and I sit on one of these anticoagulation guideline panels, and I’m really disappointed in how limited we are as far as having randomized controlled trials to guide us. I recently had a person that I know well who works at one of our hospitals who ended up in the intensive care unit with COVID and she was really struggling. We had this conversation, it looks like she was going to be heading to death actually. Her D-dimer was up at 13,000. I think I mentioned this on TWiV. She was on full-dose anticoagulation, nothing seemed to be working. We actually gave her a higher dose of steroids, and the next day the D-dimer was at 3,000.

This was an interesting moment for me to think about. Are we making her better by interfering better in an inflammatory cascade, her D-dimer is telling us about uncontrolled inflammation? Or is it really anticoagulation that’s critical here?

I’ll go into superinfections next, and this is the time when we see how much harm we may have done. I think I’ve mentioned that early on, some of the steroid-using physicians were yelled at that they would be killing their patients. The warning was that if you messed around with steroids and other things that impacted the immune system, you would see dramatically higher rates of bacteria and fungus in the blood. All this would come back and you would realize that you killed your patients with good intent. Fortunately, we haven’t seen that. That’s a little bit helpful, but it’s a recap.

Here we are in August 2020, nearing the end of August 2020, and what have we got? We have some people wearing and supporting face masks. The men always tend to have their nose stuck out. We have better access to testing, we have physical distancing. We do understand the clinical course from acute to the tail and all the wide range of presentations. I think this was a cooperative success. This was people communicating. I think this was information going back and forth.

We have remdesivir, which is something. We have steroids which are cheap, which is fantastic. This isn’t something that only certain people will be able to afford. They seem to make a difference if given to right people at the right time, but we’re still learning about dosing. Does that mild person on two liters of oxygen need the same amount of steroids as someone who’s on a ventilator? We’re not sure. We do have anticoagulation not only in the hospital but also people going home on this. We’re still working on dosing, we’re still working on patient and agent selection, and we’re still really limited as far as guidance from the literature.

I think in the New York Times article, they talked about how both sides felt a little bad. The researchers maybe felt bad about their choice of words, but a lot of the clinicians felt a little bit bad about, “Here we are in August and we still don’t have randomized controlled trials.” I guess my request to all the clinicians that listen to the early part of this is that we don’t know, and it’s very hard to know unless we can cooperate and communicate effectively with our research colleagues.

I saw the frustrations on both sides. I saw the frustration at the bedside not really knowing what it was that would help patients and seeing things thrown at patients that seem to me to be harmful. I also found the frustration as a researcher setting up these large randomized controlled trials which are not inexpensive and take a lot of time, and then seeing basically the back and forth, a certainty one week, the other week, uncertainty, the other way, but never that certainty that we need, that knowledge to help us guide patients.

I think we’re well into the pandemic. Many of us, on both sides, have regrets. I think I mentioned earlier on, the MD and the PhD, so I’m one foot in both camps, but we still don’t have the guidance that we would like. I think people have been passionate. They’ve been driven to do or to stand up for what they feel was right, but I think this is one of those times when maybe we should all step back and be a little bit humble, and realize that in medicine, it’s very complicated. It’s very hard to know what the right thing is without the science and without the studies to guide us.

I’m going to finish there, and I’m going to remind people to keep helping us out. We’re trying to support Floating Doctors down in Panama. As I mentioned, they’re having a really tough time. This organization I’ve worked with for years goes out to all these little indigenous villages and they are little. You sleep in tents, it’s 110 degrees, and you’re covered in sweat, every day you’re setting up these mobile clinics, and you’re working with these wonderful individuals.

In America, we’ve put on 15 pandemic pounds. In a lot of these areas, the people have lost 15 pounds, they’re starving to death. This organization is really helping to try to bridge that gap to supply food and medical care to these individuals. Help us, go to to donate and help us to support these disenfranchised individuals. Thank you.

[00:39:20] [END OF AUDIO]

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