What explains the strange constellation of symptoms that is “long COVID?” Will it ever go away? And why does vaccination seem to help? Writer F.T. Kola returns to the podcast Social Distance to recount her experience with long COVID with hosts James Hamblin and Maeve Higgins.
They’re also joined by Dr. Akiko Iwasaki, an immunologist investigating long COVID at her Yale lab. She explains what we know about the condition—and how two theories about its root cause mean the difference between a cure and no clear end in sight.
Listen to their conversation here:
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What follows is a transcript of their conversation, edited for length and clarity:
James Hamblin: This term, “long COVID”—or “long-haulers”—is used often. Is there a working definition or way that you describe it? Because it can encapsulate many different things, right?
Akiko Iwasaki: There lies the problem already. There isn’t a universal definition of long COVID. But I think the medical community is coming to some consensus that it’s basically a post-acute viral syndrome that happens after a person has experienced infection with SARS-CoV-2 and has had symptoms for over two months—some people say three months. That definition, again, isn’t universal. [And] for most people to be considered to have long COVID, you need to have prolonged symptoms of certain severity. For instance, many of the long-haulers have fatigue—like, extreme fatigue.
Maeve Higgins: F.T., you’ve mentioned your fatigue before.
F.T. Kola: Yeah; it’s really interesting hearing Professor Iwasaki talk about this, because one of my anxieties this whole time has been that I feel relatively okay, and I know that there are people out there with very distressing and extreme symptoms. And do I qualify as long COVID if I’m basically up and around?
The fatigue, which weirdly emerged later in 2020, meant that I would ration my week. I would have two or three days to get things done—and then two or three days I just had to black out on the calendar, because I won’t get anything done and I’ll probably just be in bed that whole time. That fatigue was surprising to me. It was a type I’d never experienced before. And I thought a lot about how, if I had had to go to a place of work or if most of my work was physical, I would not have been able to do that for over a year post-COVID. And that was mostly due to the fatigue.
Iwasaki: Exactly. That is one of the most common symptoms that people with long COVID have—this very severe fatigue. Others report brain fog: an inability to think clearly and remember things, [along with] other cognitive issues as well.
Higgins: And what about [losing] the sense of smell and taste? Is that a common long-COVID symptom, too?
Iwasaki: That is also extremely common in people who had COVID. Some people only have a loss of taste or smell as the symptom. Others have it in addition to more serious symptoms.
Higgins: What about vaccination helping people who have long COVID? F.T., didn’t [you] experience some alleviation after you got vaccinated?
Kola: Yes, definitely. The long COVID kind of went in stages. It waxed and waned over time. [And it was] surprising to me how much things melted away post-vaccine. I have my fingers crossed as I’m saying this. The fatigue was one of those things. It’s like I got an energy boost. That [fatigue] has gone away, as well as things like particular kinds of chest pain and very bad headaches. I’m curious if Professor Iwasaki knows why some things might have seemingly gone away and some things are yet to resolve—like, for example, hyposmia and hormonal changes?
Iwasaki: That’s exactly why we’re starting a study to investigate what might be underlying the symptom improvement in long COVID after vaccination. As you say, F.T., there are people reporting symptom improvements after the vaccine. And we don’t even have a handle on: What are the common things that people experience that improvement [with] after vaccination?
But I do hear people saying they have energy, and they’re not as fatigued anymore. They can breathe better. The shortness of breath has gone away. They can walk again without shortness of breath. [Before the vaccine] people tend to not be able to even walk across the room, and [then] they can. So there are a lot of different symptoms that are apparently being lifted by the vaccine.
Higgins: How do vaccines help? What is the mechanism that a vaccine would help with the symptoms of long COVID?
Hamblin: It’s kind of counterintuitive.
Iwasaki: Yeah, exactly. So in order to explain that, I think we need to introduce a couple of theories about long COVID. So, long COVID can be mediated by a persistent virus infection, stimulating inflammation in a person for an extended time period.
Higgins: So would you still test positive for COVID if that’s what it is?
Iwasaki: Well, that’s the tricky thing. Such a reservoir of virus is not likely to be in your nose, so the nasopharyngeal swab people used to test for COVID is vastly negative in the long-COVID patients. And so if that reservoir were to exist, it must be deeper in the tissue somewhere.
Higgins: So that could be hiding, and that’s what’s making you still really sick. And then is there another theory you were going to mention?
Iwasaki: Yes. The second theory is that long COVID is created by autoreactive cells, or autoimmune cells, and antibodies. And if that were the case, then the vaccine may provide some temporary relief—but may not be a cure for long COVID, because all autoreactive cells are really difficult to get rid of.
Hamblin: Is this something that you would anticipate might take years to go away, but should eventually—or might be with people indefinitely?
Iwasaki: It’s hard to say how long the long COVID will last. Based on experience with other post-viral long-term symptoms, in some people this could last for a very long time. People with other viral syndromes after acute infection have been suffering for years or decades. Hopefully that’s not the case with long COVID, that it’s a more transient thing. But we just don’t know yet.
And a lot of long-COVID people didn’t have the [COVID-19] diagnosis. Because back in early spring of last year when COVID was spreading, there were not enough tests. And so there are lots of people who are suffering from very similar symptoms as long COVID without the actual diagnosis of COVID. That’s leaving a lot of those people out of studies. And a lot of people like that are out there trying to get into post-COVID clinics and get therapy—but they don’t have the diagnosis and therefore are left out of the system.
Hamblin: F.T., you got COVID-19 during the early days of the pandemic. I don’t think long COVID was known to be something to look for then. What were you told? How does that square with what you’re hearing now from physicians?
Kola: It was so early on for me that I remember my doctors coming into my room and saying: “Well, we just got off the WHO call.” Things like that. It was changing day by day. At the very end, when I was out of the ICU and into the newly created COVID ward, I’d say something like: “I think something in my chest is weird” or “I don’t think I’m urinating in the way that I should be.” And the doctors would say what they would say for months and continue to say, really, which is: “We’re going to record everything, and we’ll test everything if you say something’s wrong”—which I greatly appreciate, because I think a lot of long-COVID patients haven’t had people believe them or haven’t had access to responsive health care, which was huge.
So they would say: “We’ll look at it, and we’ll test it, and we’ll monitor it, and we’ll watch it.” And once I got home, it was: “Come back in this many weeks, and we’ll run bloodwork.” “Come back and do a brain MRI.” “Let’s do an echocardiogram.” And this is an extraordinary amount of luck and privilege to have that medical care. But they, understandably, can’t really tell me anything.
I think the only thing that has changed is this understanding that long COVID is real. And, as Professor Iwasaki was saying, all these things are long COVID, but I still don’t know what they mean or what they are. I still don’t know why I’ve had chest pain. A few things were obvious, like having pneumonia. But most of it has been: “We don’t know why this is happening. We don’t know what that is. We believe you. We’re going to look at it, but we just have no way to know.”
And something that has been my great psychological fear is what Professor Iwasaki mentioned—that there may be a reservoir of virus somewhere still in my body. I think that’s medically terrifying, but it’s also psychologically terrifying. Because it feels like you’re living with this thing, like can it reemerge at some time and you’re not free of it. It’s like being possessed or something. So those are the two areas of mystery: What exactly did it do to me? And is it really gone?
Hamblin: Yeah, what about treatments? What’s the first step of treating long COVID?
Iwasaki: We’re hoping that our new study of the immune response in long COVID will highlight some of the pathways that we can interfere [with] to make some of these symptoms go away. For example, if long COVID is driven by persistent infection, the vaccine may actually get rid of the source of the problem altogether—because it will induce a very robust antibody response and T-cell response. And that will be a permanent cure.
But if it is autoimmunity, we need a completely different way of dealing with it—to sort of tamp down the autoreactive cells from becoming more activated. And that would require completely different kinds of therapy. Understanding the disease process itself is really important to coming up with the right therapy.
Hamblin: Yeah; that’s the same tension at the heart of a lot of treatment of acute COVID-19, too. At what point are you trying to tamp down the immune system, and at what point do you just focus on trying to minimize the virus? Because sometimes you need your immune system to eradicate that virus, and sometimes the immune system is causing those symptoms.
Iwasaki: Right—running on the theme that everything we do with COVID is about the timing. The therapy, for example, for late-stage disease is completely different from therapy against the early infection. And getting that timing right for each patient has been a real struggle. It’s something we’re learning on a daily basis.
So I’m interested in whether we should enhance the immune response to get rid of the reservoir virus or tamp it down. And I believe the answer is going to be different for different individuals. If we can come up with some sort of biomarker to diagnose who has what kind of long COVID and what the best treatment is for that person, that would be my dream come true. And to get there, we really need to understand the disease itself.