- Get CME-MOC credit with ACP!
- 04:16 Supportive Care
- 07:48 Step-up approach to oxygenation
- 13:44 Data Points
- 15:30 Clots
- 19:13 Steroid use
Part 1: Supportive Care
- Care for COVID patients in the ICU is not different than care for other critically ill patients. It depends on data collection/interpretation and regimented decision-making
- Supportive care seems basic, but is one of the most important parts of caring for COVID patients
- Supportive care falls into a few different buckets – early mobilization, removing unnecessary lines, lung protective ventilation
- The most important thing is to pay attention to their vital signs and think about basic needs of our patients – develop your differential diagnosis for things like hypotension, hypoxia, and tachycardia so that you can appropriately evaluate and treat your patients
Part 2a: Oxygenation
- Think in terms of a step-up approach to oxygenation – self proning, supplemental oxygen, noninvasive positive pressure, and mechanical ventilation
- Self proning benefits patients in a few ways – decreasing V/Q mismatch, recruiting dependent lung segments, better drainage of secretions, improved hemodynamics. Most importantly, patients feel better!
- Supplemental oxygen means everything from nasal cannula to face mask
- High flow nasal cannula is mostly supplemental O2 with a small amount of positive pressure
- Noninvasive positive pressure ventilation – usually referred to by the trade name of BiPAP – can be used with reasonable infection control. We were worried about this at the beginning of the pandemic, but can be done safely with precautions taken
- It’s ok to tolerate permissive hypoxemia if you can stave off intubating patients
- Intubation doesn’t just mean mechanical ventilation – it also means sedation, immobilization, infection risk
- The duration of mechanical ventilation can approach two weeks with a long tail
Part 2b: Labs
- Trending daily CRP, ESR, D-dimer, troponin, LDH, etc probably doesn’t provide much useful information
- If you don’t know what you’re going to do with a test result – or don’t know what you’re looking for in the first place – it may be better not to order it
Part 3: Anticoagulation
- Anticoagulation has been a source of controversy throughout the pandemic
- There is observational data suggesting mortality benefit from full-dose anticoagulation in hospitalized patients
- Remember that observational data needs to be interpreted with caution – it is generally considered hypothesis-generating and not proof.
- DVT prophylaxis is clearly appropriate
- Clinical vigilance for clots is also appropriate – think about DVT when a patient has unilateral lower extremity swelling or a PE with new tachycardia and hypoxia
- Critically ill patients can develop clots regardless of what makes them critically ill. It’s not clear that there’s something special about COVID that makes patients more hypercoagulable than other critically ill patients
Part 4: Medications
- RECOVERY trial demonstrated a clear mortality benefit from dexamethasone in severe COVID, particularly in ventilated patients
- Dexamethasone use for up to 10 days resulted in a lower 28-day mortality
- Benefit of steroids appears consistent across different trials and in a meta-analysis
- Remdesivir – a viral RNA polymerase inhibitor – seems to reduce time to recovery
- Remdesivir is best given early in course and a 5 day treatment duration is probably sufficient.
- Hydroxychloroquine does not have a role in treating COVID.
- IL-6 inhibitors, convalescent plasma, and other immunomodulators feel exciting, but we just don’t have any clear clinical benefit. Role for these treatments outside of clinical trials should be limited
- It is ok to continue ACE inhibitors or angiotensin receptor blockers. Indications for these medications don’t change just because someone has COVID and there is no need to stop them related to COVID risk.
Part 5: Recovery
- No one leaves the ICU the same as they entered. Long term effects in ICU survivors are common
- Post intensive care syndrome (PICS) can lead to significant long term morbidity
- Data on post COVID syndrome are heterogeneous and limited conclusions can be drawn, but clinicians should be aware that COVID patients may still be suffering after recovery from acute infection and hospital discharge
Greg: For many of us, the entire COVID-19 pandemic has felt like it’s occurring at warp speed.
The spread of the virus, the economic fallout, the chaotic twitter discourse, the rapidly evolving nature of evidence based treatment – it feels like a blur. When it comes to COVID, the days may be long, but the weeks go by quickly.
Marty: And here we are months into this pandemic and keeping up with the literature still feels like drinking from a firehose of new information.
Greg: So this seemed like the right time to pause and gather our thoughts to present a basic guide to treating patients infected with SARS-CoV-2 who are sick enough to come to medical attention.
I’m Dr. Greg Katz. I’m a cardiologist by training, and a past CORE-IM contributor in the cardiac realm. But during the pandemic I’ve become a COVID doctor by necessity, which makes me just like everyone else on Twitter – an experienced non-expert on SARS-CoV-2.
Marty: And this is Dr, Marty Fried, leaving the protected cocoon of 5 Pearls with Dr. Shreya Trivedi to join Greg for this important update on the treatment of patients with COVID-19.
Greg: So, I had the chance to sit down and chat with Dr. Laura Evans about an approach to taking care of COVID patients.
Dr. Evans is the Medical Director of Critical Care and associate Professor of Medicine at the University of Washington. She’s been both on the ground taking care of COVID patients in Seattle and New York, but also integral in developing systematic hospital protocols to treating these patients. She’s also the former director of Critical Care at Bellevue Hospital, where she was in charge of the Ebola response in 2015, so she’s the closest thing that there is to an expert on treating a new disease during a pandemic
Marty: So when COVID first started appearing on our ward floors and intensive care units we quickly realized that the sick patients were dying from ARDS – or acute respiratory distress syndrome. And you might remember the controversy about patients with happy hypoxia and weirdly high compliance – so we asked Dr. Evans what is so different about ARDS in these patients?
Evans: Are we really seeing that this behaves differently than the other clinical syndrome of ARDS? Or is it just that there’s so many of these patients at the same time that all of these subtle phenotypic differences that normally we just chalk up to this is just an odd case, make us think that there’s signal that this is a fundamentally a different disorder.
Greg: Right – so as reports come out about the clots and the myocarditis and the strange pediatric multisystem inflammatory syndrome, a natural question arises: is covid the weirdest disease of all time?”.
Marty: I mean, is it not?
Greg: So, I don’t think so. We’re just seeing a ton of minor individual variation. Think about it: If all you saw was TB, you’d recognize a million phenotypes. Same with coronary disease. Or anything for that matter. So really, Covid isn’t a zebra, it’s just the biggest herd of horses the modern world has ever seen.
Marty: The biggest herd of horses the modern world has ever seen. Classic Dr. Katz.
So today we’re going to dive deeper into what we know about this viral herd:
We’re going to start with drawing on Dr. Evans’ experience in treating a disease that no one has ever seen before.
Then we’ll discuss supportive care and oxygenation.
And then we’re going to turn our attention towards clots, and what we should be doing about anticoagulating these patients.
Greg: And you’ve heard about remdesevir, convalescent plasma and, of course, hydroxychloroqine – so what is the evidence basis behind these medical therapies?
Marty: And we’ll finish with what happens after you’ve recovered from this infection. What do we know about the post COVID syndrome and recovery from being sick in the intensive care unit?
Part 1 Approach to Clinical Care – Supportive Care
Greg: Once testing has confirmed a diagnosis of COVID, we get into the real work of taking care of these patients. Where do you begin? What’s the first step to taking care of patients who are dying from a disease that you’ve never seen before
Evans: I think that’s an interesting question, cause I don’t think it’s actually that different than what we do every day. So I would say kind of the theme of it was be calm and kind of stick to the basics that we know how to do care of patients. We know how to take care of patients and we know how to treat blood pressure. We know how to evaluate kidney failure, if it’s present, we know how to do these things. And so it kind of hinges on the basic skills that we learn through school and through training. And, you know, as obviously as we go through our careers and continue to learn to kind of stick to the basics.
Marty: So, as a PCP I often think of ICU care as the like the sexiest part of medicine – the patients are sick, the physiology is complicated, the interventions can be high-risk – but what i’m learning is that good care in the ICU really is about good data collection and regimented decision making.
Greg: Exactly. Critical care doctors have been the backbone of our hospitals during this pandemic. And what I’ve learned from talking to a lot of really good ones, is that high quality critical care is much more about understanding physiology and following checklists, than the miraculous save of a crashing patient.
So, what are the basics of supportive care in these patients? So what exactly should we be doing with them?
Evans: When you look back over critical care over the last couple of decades, we’ve gotten better at taking care of patients, outcomes are better and it’s predominantly through improving supportive care and improving the way we take care of patients rather than through specific therapeutics.
So we mobilize patients now much more aggressively. We get them up and moving in the ICU, we take out unnecessary central lines to avoid hospital acquired infections. We use lung protective ventilation for ARDS, and those aren’t specific treatments they’re not a specific drug or, but they all result in better patient care. And so I think kind of hinting on this, that sticking to these fundamental principles of how do you take good care of patients is probably the best approach to an unknown situation. Um, and I don’t think COVID is that different
Like we know, certainly I think it’s an unusual virus in some of the manifestations of that, but we had some early reports obviously coming out of Wuhan. And I think they did, you know, some of the early data that came out was helpful in terms of setting some expectations about what these patients might look like from that. And then kind of sticking to the basics again, going back to, okay, the first thing we want to do is just support them, support organ function, don’t hurt them and go from there.
Marty: To go back to our analogy from before – any herd of horses will have some outliers – or groups of outliers. You’ve probably heard the reports of myocarditis and circulatory collapse. There’s definitely COVID-related glomerulopathy.
Greg: But, whether a patient has COVID induced ARDS or COVID induced fulminant myocarditis, you still need to go back to the basics and treat the underlying pathophysiology. In ARDS, that means low tidal volume ventilation and in cardiogenic shock it means supporting the hemodynamics.
Evans: One of the art forms that you learn is when to not just stand there, do something and when to not just do something stand there. And that’s one of the key things that we hope to learn during our medical training is to evaluate the urgency, to not lose that sense of critical thinking and judgment and apply all the skills that we’ve learned along the way.
Greg: The toolkit that we’ve developed during medical training provides us all with the skills to rise to the occasion to take care of these patients. So in addition to the basics, let’s get into the other things that we can use starting with, supporting oxygenation
Part 2b – Clinical Care – Oxygenation
Marty: So similar to other pulmonary diseases, we approach oxygenation in patients with COVID with a step-up approach. You know this algorithm from nasal cannula through noninvasive ventilation and intubation. But what have we learned about each modality in the treatment COVID patients over the last 8 months?
Greg: Step up approach, I love it. Before we even get into extra oxygen, let’s start first with proning, also known as adult tummy time. What’s the point of proning?
Evans: We’ve been doing it, obviously in intubated ARDs patients for a while. But the use of doing it, you know, pre mechanical ventilation and, um, awake patients, I think is an interesting concept. The benefit is, you know, obviously potential improvement in oxygenation, uh, through mediated hope through better VQ matching.
Greg: For those of you that haven’t thought about pulmonary physiology for a while, VQ mismatch is when you have an area of the lungs that has gas exchange but doesn’t have perfusion or vice versa
Marty: And there are several other benefits of proning that don’t get as much air-play as matching all the V’s with all the Q’s.
One of these is sort of obvious but turns out to be a big player – recruiting dependent lung segments. So, it turns out you have more alveoli in the back of your lungs than you do in the front, so when you are laying supine all those posterior lung segment alveoli get squashed and the anterior lungs, which have less alveoli, get less squashed. This is a problem… but if prone someone you actually flip that and squash the area of the lung with less alveoli, you decompress the posterior segments with greater alveoli. The end result is more alveoli open for business of gas exchange – this is an everyone wins situation!
Greg: And we won’t get into it but there are also hemodynamic benefits and better drainage of secretions with proning. But the bottom line is that proned patients feel better.
Evans: That’s kind of what we want to do. Right. So I think if I’m a patient I’d like to feel better. And so if turning over and laying on my stomach helps me feel better, I’d be willing to try that for sure.
Marty: Agreed. Alright, The next step up is supplemental nasal cannula and facemask, both of which are fairly self explanatory: you give patients extra oxygen when they become hypoxic. So I don’t think we need to dwell on that for too long.
Greg: Next up on our respiratory support list is high flow nasal cannula. This is a lot of oxygen with just a bit of positive pressure. Like if Lacroix had a positive pressure flavor.
Marty: Sounds delicious and refreshing. And then next is noninvasive ventilation, which was actually cautioned against at the beginning of the pandemic.
Evans: Initially predominantly because of infection control concerns, and also some concern about delaying intubation and what the impacts were on patient outcomes from if you delay intubation mechanical ventilation and somebody who goes on to need it, um, people were really hesitant to use noninvasive ventilation.
Greg: So back in March, we were intubating everyone when they hit 6 liters of supplemental oxygen for two major reasons. 1) we thought that pressurized ventilation was basically spraying coronavirus everywhere and 2) we were worried about missing the opportunity to quickly intubate a patient who was crashing. But out approach to non-invasive ventilation has changed quite a bit since the beginning of the pandemic.
Evans: I think we can demonstrate it now that we probably can do this safely from an infection prevention and control standpoint.
Marty: So we also learned that (a) with appropriate personal protective equipment our healthcare workers risk was very low, even with that BiPaP-induced COVID bath they were taking… but (b) even more importantly these patients can actually tolerate a fair amount of hypoxemia. We have patients self prone with supplemental oxygen or high flow nasal cannula or we can use noninvasive ventilation. And it turns out that delaying intubation does not have this deleterious effect that we initially thought.
Greg: In retrospect that makes a ton of sense. Every intervention has risks and benefits. And putting someone on a ventilator doesn’t just mean respiratory support – it also means sedation, immobilization, and infection risk. There’s no free lunch in medicine and intubation is no different.
Evans: And I think one of the things that’s really challenging is the duration of respiratory failure in this population is really long. Oonce they’re intubated, they stay intubated for a really long time. That average duration of mechanical ventilation is probably closer to seven to 10 days with a really long tail. And we’ve all seen reports of people being on the ventilator for weeks.
Marty: Which means that if we can avoid intubation we can. And just to point out, we can make the final step up to extra-corporeal membrane oxygenation, or ECMO, if your medical center has the capability and your patient is a good candidate. This is one of the highest risk interventions we can offer, so it’s vital to choose patients carefully. Alright Greg, let sum up our respiratory support section.
Greg: Okay, so… Support oxygenation but tolerate permissive hypoxemia if you can keep the saturation in the high 80s. The tools that we have at our disposal include self-proning, supplemental oxygen, HFNC and noninvasive ventilation, all before we are forced to intubate a patient. But then once our patients get intubated, they can stay intubated for a really long time, so we need to modulate expectations of getting off the ventilator quickly.
Part 2c – Clinical Care – Labs
Marty: And while we’re trying to do a whole lot of not intubating – meaning supporting oxygenation with all the stuff Greg just mentioned – we’re getting a lot of data on these patients.
Greg: Oh, so much data. Many of us are trending daily CRP, ESR, ferritin, troponin, LDH, and d-dimer. Some people are checking interleukin levels.
But what do we need to be following and does this data collection provide us with any real clinical clarity?
Evans: So I’m going to be honest. I don’t know what to do with all those labs. I don’t know what to do with their daily ferritin. I don’t know what to do with their daily dimers. I don’t check them. They’re already really sick. So how much prognostic value does a really elevated ferritin add? And I think that’s uncertain.
We still get a lot of labs in the ICU. I’m not going to pretend that I don’t know, don’t get a lot of labs, a very robust data stream from labs. Um, but, uh, I’m not ordering labs differently in a patient with COVID-19 than I am with another ICU patient. I’m trying to use the same kind of clinical thresholds from that. Will this approach turn out to be wrong because somehow that trending the CRP makes an enormous clinical impact on these patients. I’m certainly willing to learn that.
Greg: There’s your zebra. A COVID expert who’s willing to learn that they might be wrong. [Marty: dammnn]I don’t know what to do with them either. And it’s a good lesson for the way we take care of all patients – if you don’t know what you’re looking for with a test, it’s probably not that great of an idea to order it in the first place.
Part 3 – Anticoagulation
Marty: But a question about a daily d-dimer easily segues into a discussion about thromboembolic disease. The questions surrounding clots and anticoagulation in COVID just won’t go away.
Evans: I think the question of are these patients truly more hypercoagulable than other sick patients remains unanswered. I think, you know, certainly the experience in places like New York City, where you had overwhelming numbers of incredibly ill patients, there was a lot of thromboembolic disease.
There were overwhelming numbers of really sick patients who have get thromboembolic disease, or if it was truly that this represents an increased incidence that is unique to the pathophysiology of SARS-CoV-2.
Greg: Right, we know that critically ill people get clots. [pause] The question is whether COVID patients with ARDS are more thrombogenic than patients with other etiologies of ARDS? [pause] There just isn’t really evidence to support this.
Marty: But what do we do about the clot risk that is being observed? Mount Sinai published data in JACC showing an association between full-dose anticoagulation and improved survival in hospitalized patients. Now, it was a retrospective observational study looking. The authors looked at anticoagulating patients with COVID infection and they showed patients on mechanical ventilation who received full dose anticoagulation actually had a lower risk of death.
Greg: And we’ve seen some hospitals instituted protocols where all COVID patients received full dose anticoagulation, some places have specific D-dimer cutoff that led to initiation of full dose anticoagulation. I don’t know if this was the right call or not but i’m sure there is something to learn from these clinical experiences
Evans: So I think you can, you know, you can develop an institutional pilot and then you can study that it may not be an RCT, but you can certainly study that. I think the Sinai report is really… got a lot of press. I think there’s a lot of other confounding factors that may play into that particular observation around that patients who received anticoagulation, who were mechanically ventilated, um, had higher rates of survival than those who did not the, so I think it’s, to me it’s a hypothesis generating study, not a practice changing study.
Greg: As all observational studies hopefully are — hypothesis generating but not practice changing.
Marty: Hard co-sign. Alright, so how should we approach anticoagulation in these patients?
Evans: I think just being clinically vigilant that people who are really sick and hospitalized and laying in bed, because they’re really short of breath, have risks for venous thromboembolic disease and, you know, using appropriate prophylaxis for venous thromboembolic disease is important. And I think maintaining sort of clinical vigilance that they could indeed develop a DVT or PE kind of makes the most sense logically to me as an approach rather than anticoagulating kind of across the board.
Greg: So what Dr. Evans is advocating here is thinking about the manifestations of a clot and watching out for them. Unilateral lower extremity edema should prompt consideration of a DVT. New hypoxia with tachycardia and right axis deviation on ECG should make you consider a PE.
However, the full story on anticoagulation and thromboembolic disease in COVID is yet to be written.
Marty: Ok – So what I’m taking away from anticoagulation is:
- Critically ill patients can develop thromboembolic disease regardless of the etiology of their critical illness
- Thromboembolic prophylaxis is appropriate just like in any other hospitalized patient
- Looking for clots when there’s a clinical suspicion for a clot, probably makes more sense than just anticoagulating everyone.
Part 4a – Medications
Greg: Let’s switch gears a bit and talk about steroids:
Evans: The RECOVERY trial definitely changed the game for us in terms of, of, um, use of steroids for these patients.
Marty: So, Dr. Evans here is referring to the European trial published in the New England Journal of Medicine in July 2020. This was the first high very quality study to finally show a clinically meaningful benefit – that patients with COVID on ventilators had a mortality benefit with dexamethasone… and, a fairly impressive one at that.
Evans: Um, the magnitude of effect in the RECOVERY trial, particularly on patients with, you know, um, higher severity of illness is huge and it’s bigger than what we’ve seen with steroids and basically anything else. So I have to admit like this Laura’s opinion, I personally have a little bit of skepticism that the magnitude of effect is as big as it’s reported in that trial, just because we haven’t seen that we’ve studied corticosteroids and critical illness for a really long time. Um, and there is some positive signal there, but it’s not of the same magnitude that we’re seeing, uh, reported from the RECOVERY trial. I hope it’s Epic. That would be awesome.
Greg: OK – so steroids are awesome. And to be clear, the magnitude of benefit seen in the RECOVERY trial is massive, with a number needed to treat of 8 in critically ill intubated patients with COVID, and 30 for non-intubated patients. But an NNT NNT <10 is rare in what we do, so it’s appropriate to start with skepticism. But steroids seem to be the real deal in severe COVID – these results have been replicated in subsequent trials and published collectively in a meta-analysis in JAMA.
Marty: Alright, so Who should get steroids, how much should they get, and how long should the steroid treatment last?
Evans: The signal of benefit, albeit in subgroup analysis, is in patients who are requiring oxygen, um, with bigger signal of benefit in those who are more severely ill. So those who are mechanically ventilated, those who are on ECMO, um, those who are on high flow oxygen or, or noninvasive ventilation. So I don’t think there’s a reason to withhold steroids and somebody who’s hospitalized on oxygen with COVID pneumonia.
Greg: And this makes pathophysiologic sense – ARDS in COVID seems to be related to our immune response to the virus, the cytokine storm, so tamping that down with steroids seems to improve outcomes for the sickest COVID patients.
Evans: We’re using kind of the RECOVERY trial dosing range of six, six of dexamethazone or the equivalent of another corticosteroid, daily for up to 10 days, as long as they’re still in the hospital.
It’s very likely to be a dose that’s safe, um, without serious major adverse events from it. So I think that’s, that gives you some comfort that even if it’s, if it’s not the perfect dose, what we know from the trial, that it at least appears to be safe for patients that if they’re great and going ready to go home, I would stop the steroids. I don’t necessarily know that they need to go home on oral steroids to complete 10 days of therapy from it.
Marty: So bottom line – patients who are sick with COVID-19 should almost certainly be on steroids. Greg- what else do we have in our arsenal of therapeutics?
Greg: After steroids, the other drug that’s been shown to have benefit in COVID patients is remdesivir, an RNA polymerase inhibitor that targets viral replication.
Evans: Yeah. I think Remdesivir definitely has some signal there. It does not appear to be a miracle drug.
Greg: No that’s hydroxychloroquine, that’s the miracle drug,
Evans: The act study wasn’t necessarily designed to answer all these specific subgroup questions.the primary outcome of, you know, improved time to recovery is a good outcome, but if it’s not a mortality outcome, the signal, appears to be more pronounced in terms of less severe disease. And mechanistically, that kinda makes sense to me in the sense that, you know, when, if you look, if you use the analogy of influenza and oseltamivir… is the clinical response to oseltamivir is better when given earlier in the course of influenza illness, rather than later in the course.
Greg: Since the early illness is caused by direct viral effects, it makes sense that a drug like remdesivir that blocks viral replication should theoretically have more benefit early on than it will later, on the other hand since late manifestations are caused by the immune response to the virus, a drug that tamps down the immune system – like dexamethasone – might work better later.
Evans: I think the, the recommendation to prioritize, um, folks who are hospitalized on oxygen, over folks who are on mechanical ventilation or ECMO is really appropriate because even though it’s a subgroup analysis, that’s where the signal is more prominent.
Greg: So the take away is remdesivir is given early for the less sick, 5 days of treatment is probably just as good at 10, and then dexamethasone for sicker patients on supplemental oxygen. Changing gears – There’s been a lot of debate, if you want to euphemistically call it that, in the popular press about the effects of an old malaria medicine called hydroxychloroquine. I asked Dr. Evans about her thoughts here:
Do you see any role for hydroxychloroquine?
Evans: I don’t.
Greg: Case closed. Nuff said. If you take nothing else from this podcast… please remember – hydroxychloroquine doesn’t work in COVID.
Evans: There’s been, you know, what, five RCTs now of hydroxy chloroquine and looking through them.
Greg: We’re doing them eventually one will be positive. Right. Okay.
Evans: Looking for the niche that it works, right. It does, it doesn’t seem to work for PrEP. Doesn’t seem to work for PEP.
Marty: Dr. Evans is talking about about pre- and post-exposure prophylaxis here, just like what we do with tenofovir-emtricitabine for HIV.
Evans: Uh, it doesn’t seem to impact mild to moderate disease. It doesn’t seem to impact severe disease. I think we would, you know, we would all love it if hydroxychloroquine worked.
Greg: Yeah. It would be wonderful.
Evans: That would be great. I think the reality is, is that it doesn’t.
Marty: So next time your neighbor asks you. Hydroxychloroquine is just not the miracle drug that some people would want us to believe. It’s not even a drug that seems to work on the margins. But the nice thing about this medicine is that we have good clinical trial data.
But enough about that.
What about other immunomodulatory treatments? We’ve had low quality or neutral data on colchicine, tocilizumab – an IL-6 inhibitor – we’ve heard about inhaled interferons, on anti-IL-1 treatments. What is the role of any of these therapies?
Evans: The immunomodulatory treatment with the exception of corticosteroids, I don’t think there’s a role for them at this time. The preliminary press release stuff about, you know, the IL-6 inhibitor trials are that there’s no, there’s no signal there of benefit. Um, so I’m, I’m not sure that certainly on a population basis with everybody with severe COVID, that there’s signal of benefit there, um, as there any patient that would benefit from it. I think I’d be hard pressed to say, I’m going to do this in anybody outside of a clinical trial right now.
Marty: Butttt you’re saying there’s a chance?
Greg: There’s always a chance Marty that the p-value will be less than 0.05. Let’s move on. What’s next?
Marty: We need to cover convalescent plasma…
Greg: Convalescent plasma has gotten a lot of attention.
This means taking blood from patients who have survived a COVID infection and giving the plasma – which is blood minus blood cells – to patients with COVID infection, thereby theoretically providing them with COVID antibodies. This has been a historical treatment of pandemics in the past – without evidence demonstrating either benefit or safety, I might add, but it’s been used in the 1918 Flu pandemic, and we used it to treat patients with Ebola, and now over 70,000 patients in America have received this treatment for COVID-19.
Marty: And despite this insane amount convalescent plasma that we’re now throwing around – it’s sort of hilarious when you consider that we have zero randomized controlled trials showing benefit in patients with COVID.
Evans: The convalescent plasma, I think is really interesting, you know, there is potentially some benefit there maybe. I’m hoping that people are collecting really good data on that, uh, to know, so we can get an answer for that. I mean, clearly if the plasma transfusion is not, risk-free either, whether you’re talking about transfusion reactions, TACO, TRALI, so, you know, transfusing plasma is not intrinsically a no risk prospect, but I think there’s some potential benefit from it. I think the, um, again, if you’re talking about the timing of plasma, my inclination would be as it’s probably more likely if give to benefit if given early, before the antibody response, when the patient still has higher level, higher viral loads, rather than once there’s very, very, very ill in the ICU, potentially just from the inflammatory sequelae rather than from the sort of direct viral, um, invasion of the cells.
Marty: One of our reviewers Dr. Nick Mark pointed out that the ONLY disease that convalescent plasma has worked on is Argentine hemorrhagic fever… which is a little upsetting because I have been telling all of my friends who conquered COVID that after they get better they have an obligation to donate plasma… so that advice isn’t really aging well
Greg: Unless they also have Argentine hemorrhagic fever…. but yeah definitely not for COVID, at least not yet.
And just to point out – taking care of a patient isn’t just about the new medicines that you use to treat them in the hospital, you also need to make a decision about what to do about a patient’s other medical problems as well as their home medications.
Marty: Right we learned fairly early on that SARS-CoV-2 enters cells through the ACE2 receptor – and I had patients ask over and over again if they should continue ace inhibitors and ARBs. You can make a biologic plausibility case in either direction. The case for them – blocking these receptors may decrease viral entry into a cell. The case again them – you upregulate your ACE2 receptors when they’re blocked so these medications may increase viral entry into the cell.
So what the heck should we do with them?
Evans: The NIH recommended NIH guideline recommendation is to continue them, you know, unless there’s a contraindication to do so, so right. Unless they’re hypotensive, et cetera, but otherwise to continue home meds and follow.
Greg: We have randomized, controlled trial data demonstrating that if your patient is on an ACE or an ARB that continuing those medications in the setting of COVID infection doesn’t impact mortality or length of hospitalization.
Marty: Ok, let’s bring home the section on medications. Dexamethasone for sicker patients has the largest effect size that we’ve seen, and remdesivir, the anti-viral seems to help if started quickly in the course of the disease. Despite widespread adoption, we’re not sure if the convalescent plasma juice is worth the squeeze… unless of course your patient with COVID also has Argentine hemorrhagic fever.
Part 5 – Recovery
Greg: Let’s move on to what we should do when these patients have finally survived a long hospital stay. What do we know about post COVID syndrome? The data is frankly all over the place and not that helpful. There are reports of somewhere between under 10 and more than 50% of patients developing long term, meaning post 3 months, pulmonary manifestations.
Marty: And honestly things that matter ot my patients beyond the respiratory issues – I have patients who still can’t taste chocolate or coffee months after getting COVID… so yeah, there is a population of people who are experiencing long-term issues and we just don’t know enough yet about who those are and what the spectrum of issues looks like.
Greg: So what does the post-COVID syndrome look like and how should we be preparing patients for it?
Evans: Um, another one of the great unknowns is what does this look like? We have some good data about longterm outcomes for survivors of ARDS and obviously non COVID related. It’s all proceeds COVID, um, and other critical illness syndromes, right? So there’s, there’s more and more being published about this concept of the post intensive care syndrome or PICSl which shows you that. And I think one easy way to summarize it as nobody comes out of the ICU unchanged, um, and there may be really long lasting effects from it, whether it be the effects of delirium on cognitive and executive function down the road, most of these patients did not have longterm pulmonary, uh, consequences from ARDS, but they did have longterm neuromuscular consequences presumably related to yeah, just prolonged ICU stay neuromuscular failure as a manifestation of multiorgan failure. So we’ll, COVID behaves the same way. I don’t know. I think really good general medical followup, symptoms assessment, I think a six minute walk is a great sort of tool for lots of different functional, issues and people who survived the ICU.
Greg: We’ve covered a lot of ground here – supportive care, oxygenation treatment, the miracle of hydroxychloroquine, and what happens after discharge. Some concluding thoughts from Dr. Evans:
Evans: I guess I would come back to where we started, which is just to like, stay calm, don’t lose your ability to think things through critically. Try not to get kind of overwhelmed by this sense of clinical urgency. That’s driven from uncertainty and to really, you know, come back to the center back to those basics of how do I best support this patient if they didn’t have COVID and use that as sort of a building block to go from there.
Greg: So in the past few months, we’ve all spent countless hours thinking about our patients dying from COVID. With the dizzying pace of new information, it’s easy to feel like our practice patterns need to adjust to every new data point.
Marty: As doctors, it’s always tempting for us to want to play with our shiny new toys because why shouldn’t the novel coronavirus be treated with an arsenal of novel treatments?
But at the end of the day, we’re treating patients who are made sick, incredibly sick from a respiratory virus,
Greg: And so the conclusion message is that we can do this. Our medical training has equipped us all with the knowledge and skills to do right by our patients in the biggest public health emergency of our lifetimes. After months of struggling through this pandemic, we’ve learned the best way to treat COVID is by working as a team and falling back on the fundamentals.
Marty: And with that’s a wrap for today’s episode. If you found this episode helpful, please share with your team and colleagues and give it a rating on Apple podcasts or whatever podcast app you use! It really does help people find us!
If you want to add any of your own tips or share challenges, tweet us and leave a comment on our website page, on instagram or facebook page Thank you to Dr. Salim Naajar for the accompanying graphic, to Solon Kelleher for audio editing, to peer reviewers Drs. Avrham Cooper and Nick Mark.
As always we love hearing feedback, email us at firstname.lastname@example.org. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.
- Acute Respiratory Distress Syndrome Network. (2000). Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New England Journal of Medicine, 342(18), 1301-1308.
- Thompson, A. E., Ranard, B. L., Wei, Y., & Jelic, S. (2020). Prone positioning in awake, nonintubated patients with COVID-19 hypoxemic respiratory failure. JAMA Internal Medicine.
- Scholten, E. L., Beitler, J. R., Prisk, G. K., & Malhotra, A. (2017). Treatment of ARDS with prone positioning. Chest, 151(1), 215-224.
- Grasselli, G., Zangrillo, A., Zanella, A., Antonelli, M., Cabrini, L., Castelli, A., … & Iotti, G. (2020). Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. Jama, 323(16), 1574-1581.
- Paranjpe, I., Fuster, V., Lala, A., Russak, A. J., Glicksberg, B. S., Levin, M. A., … & Zhao, S. (2020). Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. Journal of the American College of Cardiology, 76(1), 122-124.
- RECOVERY Collaborative Group. (2020). Dexamethasone in hospitalized patients with Covid-19—preliminary report. New England Journal of Medicine.
- Sterne, J. A., Murthy, S., Diaz, J. V., Slutsky, A. S., Villar, J., Angus, D. C., … & Dequin, P. F. (2020). Association between Administration of Systemic Corticosteroids and Mortality among critically ill patients with COVID-19: a meta-analysis. Jama.
- Beigel, J. H., Tomashek, K. M., Dodd, L. E., Mehta, A. K., Zingman, B. S., Kalil, A. C., … & Lopez de Castilla, D. (2020). Remdesivir for the treatment of Covid-19—preliminary report. New England Journal of Medicine.
- Guérin, C., Reignier, J., Richard, J. C., Beuret, P., Gacouin, A., Boulain, T., … & Clavel, M. (2013). Prone positioning in severe acute respiratory distress syndrome. New England Journal of Medicine, 368(23), 2159-2168.
- Gattinoni, L., Pesenti, A., & Carlesso, E. (2013). Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure: impact and clinical fallout through the following 20 years. Intensive care medicine, 39(11), 1909-1915.
- Scholten, E. L., Beitler, J. R., Prisk, G. K., & Malhotra, A. (2017). Treatment of ARDS with prone positioning. Chest, 151(1), 215-224.
- Wunsch, H. (2020). Mechanical Ventilation in COVID-19: Interpreting the Current Epidemiology. American Journal of Respiratory and Critical Care Medicine, (ja).
- Goyal, P., Choi, J. J., Pinheiro, L. C., Schenck, E. J., Chen, R., Jabri, A., … & Hoffman, K. L. (2020). Clinical characteristics of Covid-19 in New York city. New England Journal of Medicine.
- Bikdeli, B., Madhavan, M. V., Jimenez, D., Chuich, T., Dreyfus, I., Driggin, E., … & Tang, L. V. (2020). COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 75(23), 2950-2973.
- Paranjpe, I., Fuster, V., Lala, A., Russak, A. J., Glicksberg, B. S., Levin, M. A., … & Zhao, S. (2020). Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. Journal of the American College of Cardiology, 76(1), 122-124.
- Ruggiero, H. A., Pérez, I. F., Milani, H. A., Barri, A., Val, A., Maglio, F., … & Tallone, J. C. (1986). Treatment of Argentine hemorrhagic fever with convalescent’s plasma. 4433 cases. Presse medicale (Paris, France: 1983), 15(45), 2239.
- Gandhi, R. T., Lynch, J. B., & del Rio, C. (2020). Mild or moderate COVID-19. New England Journal of Medicine.