Everything We Know About Long COVID

John Whyte, MD; Eric Topol, MD


September 14, 2022

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John Whyte: Welcome, everyone. I'm Dr. John Whyte. I'm the chief medical officer at WebMD, and I'm joined today by my good friend and colleague, Dr. Eric Topol, editor-in-chief at Medscape. Dr. Topol, great to see you.

Eric Topol: Great to be with you, John, as always.

Whyte: You know, we've been talking about COVID for more than 2½ years, and now we're starting to see this – I'm going to call it a syndrome, may not be the right term – but long COVID. Let's take a step back for a minute and explain to our audience what we mean by long COVID.

Topol: Right, well, we became aware of its existence pretty early on in the pandemic because people that were infected confirmed in March and April of 2020 they were still having symptoms – significant and often disabling symptoms – many months later. And so now, over the course of this much longer span, John, we're talking about somewhere in the vicinity of at least 10% of people that have duration of symptoms for more than a couple of months, sometimes indefinitely.

And these symptoms are a mosaic. Some of it's more just profound fatigue and can be breathlessness and brain fog. In others, it can be that they have very rapid heart rates when they just stand up and that they have poor exercise tolerance. But the common theme is that these are disabling symptoms, that they often are interfering with a person's daily life activities and getting back to work. And it doesn't appear that it's just one condition. It looks like there's multiple things that overlap. Of course, there's many theories for what has happened.

Whyte: What is the theory? Because, in some ways, it's kind of like where we are – and tell me if you disagree – like where we were with chronic fatigue syndrome, perhaps, or fibromyalgia, initially, where some of these symptoms are nonspecific. They can be related to other issues. But when you pull them all together, and you connect it – the medical term is the post sequelae, the symptoms that persist after coronavirus infection – there's a rationale. So what are some of the current thinking of why this is occurring? It can't just be inflammation.

Topol: Well, the part that is, I think, probably most explainable are their immune features. There, we're talking about the symptom complex, like the brain fog, things that ring of autoimmunity; so, for example, those symptoms that more women have because they're more prone to autoimmune conditions.

And so the question is, it actually autoantibodies directed against the person's own proteins? Or is it an immune response to remnants of the virus that are stuck? Like, for example, we have many studies now that have shown the virus or remnants of the virus reservoir in the small intestine and the gut and other places in the body.

So one part of this appears to be an immune-mediated story. But then there's other things like, for example, the evidence of microclots. And then there's this whole issue of the vagus nerve or so-called dysautonomia, whereby this very pronounced heart rate response, where you just stand up, and your heart rate goes 120 or something. So that's why the lumping together of all of this is a little bit unfortunate, because it's probably more than a couple of conditions. And some people have all these symptoms, by the way.

Whyte: And it can be debilitating.

Topol: Yeah. Oh, gosh, yeah. You know, I have colleagues and athletes that, once they got afflicted, they've never been right, and they have very low energy. They can only work at certain times. And, by the way, one of the things we do know in general: If you exercise, you push too hard, you can make things worse.

So no, there's a lot of mysteries here. We have no effective treatment – lots of things that have been touted as treatments, but we're at a loss for having nothing to offer and not having unraveled the biology or the pathophysiology.

Whyte: How do we help viewers even put this on their radar screen in terms of a lot of the doctors really aren't that familiar with it, in terms of diagnosis? As you said, we currently don't have any type of specific blood test to identify it. So how do we get to that first step of diagnosis?

Topol: Yeah that's tricky, as you say, John, because we don't have a blood test. We basically – it's a symptom complex, and it's based on someone having a COVID infection or antibodies to the virus to know that they were exposed. And, interestingly, a person can be fully recovered and say, ah, I got that behind me. And then a few weeks later, all these symptoms crop up.

So the problem we have here is, in 2½ years, while we made so much progress, for example, on vaccines, we have made so little progress on this. And everything was fixated on deaths and hospitalizations. But here, we have a much bigger group of people, tens of millions around the world that have been affected like this, and we have little to offer them. Now, as you're well aware, we have seen around the United States and other countries these transdisciplinary long COVID clinics that have –

Whyte: Not a lot of them, though, unfortunately.

Topol: Yeah, well –

Whyte: A few of them. Mhm.

Topol: We have one at Scripps. Obviously, many health systems – Mount Sinai has a very active one in New York, where you are today. I think this, of course, is helpful because it's by having all systems covered, all the different specialties, hopefully, we can understand the condition better and eventually come up with effective treatments.

The only thing we do know is, if you prevent an infection, you can't get long COVID, and if you get a vaccine, especially keep up with the boosters, the chance of you getting long COVID is markedly reduced.

Whyte: But what do you say, Eric, to people that are watching, who have long COVID, or they're a caregiver of someone with long COVID? And they say, you know what, Dr. Topol? I need help. I want help, right?

So, at one point – correct me if I'm wrong – we thought, maybe if you got a booster, or if you got vaccinated right after the fact, that seemed to help some people, but I'm not sure that has panned out. What's the latest in terms of, do we just try to treat underlying symptoms? You know, any symptom – that's never an ideal process. So what's the practical advice that we can tell people now?

Topol: Well, it's really frustrating because we don't have much to offer except, if you can get to a transdisciplinary, interdisciplinary clinic, that's your best bet because you won't be just seen for one aspect of your holistic health issues. But no, our problem right now is we have so little to offer.

We have some treatments that are being assessed, like Paxlovid. Could that help? Because, for example, if it's virus remnants. We're also seeing immunosuppressants being tested. If it's an autoimmune underlying underpinning. So –

Whyte: But we want to do those in a trial or center because all of these drugs have consequences. And you and I have –

Topol: Exactly.

Whyte: – talked about how people are very much in the point that they just want to try anything, but that can have risk as well.

Topol: Well, your point is well-taken because, in the trials, half the people are getting placebo – double-blind, so they don't know what they're getting. And what you don't want to do is take things that are unproven. So, for example, if you take an immunosuppression drug now, that could set you up for liabilities for all sorts of side effects and infections. So you want to be really careful about taking things that have not been shown to be effective. And this is, unfortunately, the classic thing where we don't have a treatment, so people just go for anything, and that isn't a good idea.

Whyte: Now, I want you to help me clear up a myth – so if I say it wrong, please correct me – that there was a belief early on that people that got long COVID had severe infection. But now we're starting to see, even in very mild – and these are somewhat subjective. I mean, we have terms, but for most viewers – but even a mild case can still result with long COVID. Is that correct, Dr. Topol?

Topol: This couldn't be more important to emphasize, and I'm glad you mentioned it. So the miscue has been, oh, it's only proportionate to severity, when most of the cases, proportionally, are people with mild or, at worst, moderate COVID. And frankly, it's the reason that I don't ever want to get COVID, because it's unpredictable. You don't know who's going to get it, long COVID. And so the best thing is you just keep it away.

We do know that, with Omicron, there was about a 50% to 70% less frequency of long COVID so far, compared with Delta. However, because Omicron led to an order of magnitude more infections, it led to lots of long COVID as well.

But no, this – like I said, most of it's in people with mild cases. And so you say, oh, I only had a few days of sore throat or cough, and I'm great. And then boom, days later, that's when you start getting hit with these other symptoms. It's really important that no one is immune to getting long COVID. We don't know what break it. You know, I mentioned that there is some preponderance of women with this autoimmune subset. But other than that, it's hard to predict who's going to be getting it.

Whyte: So what do you say to a viewer who's suffering from long COVID – we can talk about enrolling in a clinical trial, trying to go to a center that is multidisciplinary. But say, for whatever reason, they can't do any of those things. Should they see a specialist based on their most bothersome symptom, meaning, if they're having shortness of breath, cough, they may see a pulmonologist. But we know that's not ideal care either. So, to those viewers who are suffering, what's your advice today?

Topol: Well, one thing I think would be worthwhile is to join one of these patient advocacy groups, whether it's long COVID Survivor Corps, Body Politic. I mean, these are helping each other in terms of one person gets insights and helps transmit to others. They're genuine. They're not misinformation conduits. That would help.

But now, outside of that, like you said, if there's a particular symptom that's dominant that's the problem, you could at least get attention for that. This is a very sticky issue. I wish we had more progress being made. It's really disconcerting.

Whyte: But what needs to be done? Do we need to be advocating for more research dollars? Do we need to think about the regulatory approval process? This is a global issue, not just the United States.

Topol: It's global. Yeah. I think, as you know, I'm a big proponent of individualized medicine. And we haven't taken that approach is to nail down in the person what is attributable, what caused the symptoms, because if we don't get to that level, and if we just treat it – long COVID, long haulers – they're all the same, and we want to think there's some kind of magic pill. We're not going to get anywhere.

This is going to be highly tailored for that person's symptom complex. And it could just mean giving the body a chance to heal and going into low-energy modes, energy-saving mode in some people. And in others, that could mean taking immunosuppression drugs. Who knows? But we need to get an approach that understands each person's unique underpinnings of their symptom complex.

What I would like to see, John, is the specific subgroup names, like the autoimmune form of long COVID or the dysautonomia long COVID, where we break it down into clusters. And the U.K. has proposed there's four major clusters, but something like that, because the way it's lumped together right now is just going to be more challenging to get to prevention and treatment.

Whyte: Yeah, but we need to keep having these conversations because we need to be giving people also the resources that they need, even if there's not something today, that they can take to address it.

Dr. Topol, I want to thank you as always for taking the time. Everyone should follow you @EricTopol on Twitter. It's one of the best things out there in terms of what's happening with coronavirus, as well as all things precision medicine in many ways. So thank you, Dr. Topol.

Topol: Thanks so much, John. I really enjoyed the conversation. I wish we had more positive things to transmit. But, hopefully, someday we will.

Whyte: Thanks, Dr. Topol.

Topol: Thank you.

This interview originally appeared on WebMD on September 13, 2022

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