Getting a Head Start on Treating Long COVID

The onslaught of long COVID could have been predicted as soon as it had been determined that the mysterious outbreak of a condition with pneumonia like symptoms in Wuhan, China at the end of 2019 was indeed a virus, says Jamie Seltzer. Seltzer is the director of scientific and medical outreach for #MEAction, a patient advocacy organization for people suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here’s something else she predicts. Long COVID will quadruple the number of people suffering from MC/CFS. She wants the National Institutes for Health (NIH) to make the battle against long COVID also the battle against ME/CFS. Instead of starting from scratch in researching long COVID, Seltzer and her organization calls upon the NIH to tap into the years of research conducted by #MEAction. For instance, ME/CFS experts have long known that the idea of having patients “push through” the malaise associated with ME/CFS with graded exercise is counterproductive. “There is now abundant research showing that pushing through this disease not only doesn’t work, but it appears to make patients worse off, possibly in the long term,” Seltzer tells Infection Control Today^®. “Some of the long COVID clinics are pushing graded exercise because that’s simply what they’re familiar with.” In addition, she worries that the absence of a virus in patients who’ve recovered from COVID-19 will imply that long COVID shouldn’t be a problem. “It’s the immune response itself that can cause the symptoms of the disease,” Seltzer tells ICT^®. “And that does not require that the virus is still there or active at all.” She adds: “People with long COVID and people with ME/CFS need to join hands and advocacy and fight together.”

Infection Control Today^®: What myalgic encephalomyelitis/chronic fatigue syndrome—or ME/CFS, or even more abbreviated, ME?

Jamie Seltzer: ME/CFS is classified as neurological. It is often post-viral. Patients report infectious symptoms around onset 80% of the time. And it’s what we call a chronic complex disease, meaning that it presents in every body system and has to be monitored and managed day to day, often by the patient who does not have a great deal of clinical support for the problem.

ICT^®: When did your group first take notice of long COVID? When did it first appear on your radar and you said, “Hey, there’s something here that we recognize”?

Seltzer: It was before people started recording long-term symptoms to be frank. Considering that ME is one of the possible consequences of viral infection, when we learned that there was a pandemic, we already knew to expect millions of individuals experiencing long-term symptoms. We brought up the topic before the name long COVID existed.

ICT^®: How many patients have been diagnosed with ME before COVID arrived? And how many more now—now that COVID-19 has been here for two years—will be diagnosed with ME? COVID-19 will swell the ME rolls, right?

Seltzer: It really will. There are multiple kind of issues of context that we need to discuss before we can answer what seems like a straightforward question. ME goes undiagnosed, up to 90% of the time, because clinicians aren’t taught about it and don’t recognize the symptoms for what they are. I still encounter everyday people who consider chronic fatigue syndrome to be the one symptom of long-term fatigue. And of course, ME/CFS has diagnostic

Jamie Seltzer, director of scientific and medical outreach for #MEAction.

criteria that require multiple symptoms. The cardinal symptom of which is post-exertional malaise [PEM] and not even fatigue. Post-exertional malaise is when patients experience a flare of symptoms, or the appearance of new symptoms after physical or cognitive overexertion. And there’s often this very characteristic 24-hour delay between the trigger and experiencing this sometimes incredibly debilitating symptom or series of symptoms called PEM, oftentimes after patients have overdone it, they can’t even sit up in bed. The fact that this is an unrecognized symptom, and that even many clinicians don’t know the cardinal symptoms, means that they don’t recognize it when they see patients in clinics who present with ME/CFS. We do have excellent medical education out there but clinicians are busy. Many of them were educated back in the ’90s, when there were derogatory terms like yuppie flu used for people who had these diseases. And so, while there up to 2.5 million sufferers of ME/CFS in the United States pre-pandemic; the majority of them don’t know what’s wrong with them. We expect those numbers to—I hate to even say it because I worry your viewers will think I’m exaggerating—but I’m actually being conservative. We expect the number of people with ME/CFS to triple or quadruple due to the pandemic alone.

ICT^®: How long have we known about ME/CFS?

Seltzer: There’s a sincere disconnect in logic, as far as I’m concerned, because we’ve known about this as long as we’ve been recording symptoms of diseases. If you look into medical history, you’ll find literature from the 1870s on post-viral neurological symptoms and syndrome. There was post-polio in the past. Recently, there’s a Spotify issue that may have made some people aware of this. Because famous singers [Neil Young and Joni Mitchell] recently left Spotify because they had post-polio syndrome. There is also post EBV [Epstein-Barr virus]. And now there’s long COVID. And each time this happens, we treat it as though it is a unique, distinct phenomenon that has never occurred in the history of the world. It’s very puzzling. Now, while some of these post-infectious syndromes have slightly different characteristics, that’s probably due to the nature of the virus or pathogen itself. Sometimes you have liver damage as a post EBV complication. You might add that to the pile of potential symptoms that people have after EBV. They might have liver damage and ME/CFS. If you look at long COVID people who are now meeting ME/CFS criteria, they may have lung damage or kidney damage, and ME/CFS. If you look at polio, you had muscle wasting and nerve damage, and you might have ME/CFS. We’ve known about this all the time. But we’ve made the rather blinkered assumption, that each time it’s actually something completely different and unique to the pathogen at hand. That doesn’t seem very logical to me. It’s not very logical if you look at the historical records from previous outbreaks. And that leads me to the answer to your next question. When we tried to talk to government officials, we were urged caution over and over again. “Well, there’s no telling that this pathogen will also initiate post-infectious complications.” That’s not cautious. That’s simply illogical. We have so much history—recent history as well as 100 years ago—to tell us that it would be incredibly unusual and atypical if SARS-CoV-2 were the only viral infection that did not lead to post-viral complications. I even hear researchers and clinicians these days saying, “Well, you can’t say for sure that this one will lead to ME/CFS.” I’m mean, I suppose not. If we’re writing a logical proof, I suppose not. But if we’re going by past is prologue, it’s very nonsensical to assume that this one virus will be the one which does not. I think that there is a group of people who lean toward that kind of thinking, especially in diseases that are more prevalent in women, which ME/CFS and long COVID both are. There is this lingering poison of the idea of hysteria, and some people never grow past Freud. However, I think that that is an unpopular point of view. And certainly it’s quite easy to show that these diseases are embodied. I even feel odd saying that because, of course, mental illness is embodied as well. And that’s a completely separate conversation. First of all, when people say that we don’t see the virus, the virus itself does not have to linger in order for there to be lasting symptoms. While there are some viruses that go latent, and reactivate, and we talked about EBV, you know, earlier, and EBV does that: It reactivates under stress. It’s possible that SARS-CoV-2 can go latent and reactivate when the patient pushes themselves physically or cognitively. I think that that’s a reasonable hypothesis. It’s the immune response itself that can cause the symptoms of the disease. And that does not require that the virus is still there or active at all. Women’s and men’s immune responses are very different. And that would be a very reasonable thing to say that perhaps women are more likely to develop these conditions because their immune responses are quite different. And we see in metabolomics, in immune function, in endocrine function, all of the things that we would expect to find in a disease of this stripe. If you say that nothing is off in your regular blood values, that doesn’t mean much to a researcher or researcher clinician. And it shouldn't. Not everything is going to show up on CBC [complete blood count].

ICT^®: Do you feel that the presence of long COVID will drag ME/CFS more into the mainstream discussion? Will it make more experts see it as a reality? Or is there a chance of it going the other way? Could ME/CFS make people start to doubt that long COVID actually exists?

Seltzer: I think, unfortunately, a lot of it depends on what happens next. We’ve seen this before. If you look at the way that people behaved during the 1918 influenza pandemic, and you can see a lot of similar attitudes and behaviors today with the SARS-CoV-2 pandemic. People don’t change. Their way of thinking doesn’t change. People are people throughout history. People are strongly attracted to easy and simplistic answers. I think that it is very easy to dismiss a group of people who become ill but don’t die after a virus that other people either die or recover from. Even with the millions of people who are going to go on to be affected by SARS-CoV-2, long COVID folks will be in the minority overall, regardless. This is an unusual thing to happen in terms of nine people are going to be OK, one of them is going to be sick forever. That’s where the psychosomatic explanation comes into play. In order for healthy people to feel safer, they’ll say to themselves: “Oh, there must have been something wrong with that person in the first place.” Or maybe, “They don’t want to be better.” Or maybe, “They just need to have a better attitude.” Because that makes people feel very safe. They can then say to themselves: “If I were to get sick, I would simply do more yoga, eat more kale, and be cheerful. And then I would be well.” I think in order to overcome that inherent necessity to feel safe, people with long COVID and people with ME/CFS need to join hands and advocacy and fight together. And we are. I think, though, that it’s also a great grief and a great tragedy for people to become chronically ill in this country and recognize that there’s very little help for them, very little support for them. And that people would rather be dismissive up to and including their clinician, sometimes, in order to feel like the world is a little bit more safe and a little bit more controllable. So, to summarize, I think we must fight together for better funding. We also have to fight to include ME/CFS in long COVID studies, because right now the NIH [National Institutes for Health] is saying things like “research on long COVID will trickle down to people with other post-viral complications.” But if you’re in science, you know, that’s not actually possible unless you research both groups at the same time under the same conditions.

ICT^®: How much is this a function of our health care system being so attuned to acute care and—though it’s gotten much better in recent decades—but not focusing as much on chronic conditions? Does that play into this at all?

Seltzer: I think it does. I think that whether we realize it consciously or not, a lot of clinicians are there to either save the patient or fix the patient. There is a lot that a clinician can do for somebody with a chronic illness. They can help improve quality of life so much with symptomatic treatments and activity management techniques like pacing, for example, which is activity management advice that means to be active when you’re able to be active, and rest when you’re exhausted. And to plan rest ahead of strenuous activities. It’s a primary activity management strategy for ME/CFS. And it seems to help people feel better most. But that is really outside of the way that we think about medicine, that you might have the same patient and they show up every couple of months. And you just check their meds and see how they’re doing and you talk to them about how they’re feeling. But you accept that you’re never going to fix them. I think that we genuinely struggle with that both conceptually and within the system of medicine that we use. Certainly for these types of conditions we do. Sometimes I wonder why that’s OK for people with cardiac issues or diabetes, but people with chronic complex disease are a bit left out of that picture.

ICT^®: You’re asking the NIH to utilize your expertise as an organization. How is that lobbying effort going at the moment? Do you think you’ll get a breakthrough?

Seltzer: Hmm. I think that that depends on too many variables. I would say that, generally speaking, when long COVID became a big deal and a headline on the international stage, researchers at very impressive institutions with very impressive roles first became interested in post-viral disease. And that’s wonderful. And we all welcome them to the field, and we hope that they’ll stay. At the same time, there are people who have been working in ME/CFS or POTS [postural orthostatic tachycardia syndrome] which is another often post-viral complication. And they have the knowledge and experience required to be foundational to these efforts. It is so odd how often I see people reinventing the wheel and stating information about long COVID as if it’s surprising or new when we already knew this or thought about ME/CFS or POTS. I think that part of the issue is the stigma that these diseases have had in the past. And new researchers to the field saying, well, that ME/CFS stuff, I learned back in the 1990s that it was just stressed rich women—usually stressed rich white women—which I find particularly awful. Considering that BIPOC [black, indigenous, and people of color] women are slightly more likely to be affected. And because of that they’re not seeking the expertise that they need in order to do the right research in the right way to measure outcomes that matter to patients most. And that will have the greatest possibility of affecting the quality of their lives. This is not a conversation about hierarchy or ego. It’s a conversation about the fact that 25% of people with ME are housebound or bedbound, only 13% can work full time. People with ME have the lowest quality of life of people with any disease to which I’m aware it has ever been compared, including things like cancer and kidney failure. These people have been waiting decades for research. And without collaboration with the researchers and clinicians who have been here all along we stand to repeat the same mistakes and we’re wasting time.

ICT^®: My readership covers a broad swathe of professionals in hospitals, including infection preventionists, environmental services teams, vascular access professionals, operating room personnel, and sterile processors. Would they have a dog in this fight? Why would they? They’re there to stem the tide of infection as it’s happening.

Seltzer: Oh, they have the dog in this fight. The fewer people who catch the infection, the fewer people are going to develop post-viral disease. And it really matters [because] it does appear that there are some pathogens that are more or less likely to lead to post-viral complications. And all the coronaviruses, the research has shown that they have a higher turnover rate. These are again small studies funded very poorly, right? But SARS and MERS and SARS-CoV-2 have all shown a turnover rate of between 25% and 33% for long-term symptoms. That’s unusual. Two small studies now say about half of those people meet ME/CFS criteria. The less we can see of infectious spread, the less we’re going to deal with people who are disabled for the rest of their lives. And the less we’re going to have yet more people out of the workforce as caregivers because those people at home need help. I think it’s very interesting that we haven’t seen … I think I’ve seen maybe one article mention that our workforce drop could be due to long COVID. Everyone says it’s not enough the number of people who have died [to have caused the workforce drop]. And that’s true. But if you consider that based off of how many people have gotten long COVID and are unable to go back to work, that really needs to be factored into our overall situation.

ICT^®: Is there anything that I neglected to ask you that you think is pertinent and that you want health care professionals to know about this subject?

Seltzer: There is one thing that we haven’t discussed yet, which is the idea of graded activity. I mentioned pacing briefly. There is now abundant research showing that pushing through this disease not only doesn’t work, but it appears to make patients worse off, possibly in the long term. Some of the long COVID clinics are pushing graded exercise because that’s simply what they’re familiar with. And again, they’re unfamiliar with the literature and unfamiliar of the history of these diseases. Post-exertional malaise appears to be a metabolic or immune reaction or both. It is not possible to simply push more and more exertion on the patient and have them regain ability. ME/CFS is not in any way deconditioning. And I would say that for most patients who do have some mobility, they are not particularly deconditioned. In order to use a metaphor that I hope will hammer this home, presuming that you can fix this disease by pushing activity is akin to putting a bigger pile of sugar in front of a diabetic every day and believing that will cure their diabetes. This is a metabolic problem and it’s measurable. And in fact, the way that people typically measure disability is with a two-day cardiopulmonary exercise test. Wherein when you put a patient with ME through a cardiopulmonary exercise test on day one, wait 24 hours, and then repeat. They lose ability. This is very unusual. Their VO2 [volume of oxygen consumed by the body in 1 minute] decreases. Their workload is less. Even other sick people don’t do this. This is something that measures post-exertional malaise and appears to be unique to people with post-exertional malaise which is people with ME and many people with long COVID. The patient led research organization which is part of body politic or arose from body politic found that the vast majority of people in their in their group—which is thousands of people—experience these issues. More than three quarters.

This interview has been edited for clarity and length.