Long COVID research after the public health emergency ends : Short Wave The COVID-19 public health emergency has ended, but millions across the globe continue to deal with Long COVID. Researchers are still pursuing basic questions about Long COVID — its causes, how to test for it and how it progresses. Today, we look at a group of researchers studying the blood of some Long COVID patients in the hopes of finding a biomarker that could let physicians test for the disease.

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Long COVID scientists try to unravel blood clot mystery

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You're listening to SHORT WAVE from NPR.

Hey, everyone. Emily Kwong here with Anil Oza, science writer and former SHORT WAVE intern. Hey, Anil.


KWONG: So around the world, public health officials have really started to wind down their responses to the COVID-19 pandemic. The World Health Organization officially ended the COVID global health emergency. The U.S. has ended its pandemic state of emergency. But the fact remains - many, many people are still dealing with the effects of this virus and with long COVID, in particular. So today, we're going to talk about it.

OZA: And, Emily, I've been following around some researchers recently who are basically bootstrapping their research that could help identify if someone has long COVID and, potentially, how to treat it.

KWONG: OK. Well, let's start with the science, and we'll get to the bootstrapping part later. What did you learn?

OZA: Well, long COVID is a huge and a growing problem...

KWONG: Yeah.

OZA: ...But we still don't have a biomarker, meaning you can't go to a doctor's office and test for it specifically. And this network of researchers are looking for clues in the blood of long-COVID patients. One of the labs working on this is here in New York. So producer Margaret Cirino and I paid a visit.




My name is David Putrino. I am the director of rehabilitation innovation for the Mount Sinai Health System.

OZA: So we started off in his clinic, where he sees a lot of these patients here in the city to help treat their symptoms. But on this day, he had taken the blood of some of those patients to look for these things called microclots.

KWONG: So are those, like, mini versions of blood clots, like, clumped-up blood cells?

OZA: Kind of, yeah. He and other researchers are seeing that a lot of these long-COVID patients are turning up with these microclots floating around in their blood. Some of them are big enough to gum up very small capillaries.

KWONG: That doesn't sound good. OK.

OZA: And one of the members of Putrino's lab took us through this process they use to separate out blood to find these clots along with another potential compound they're looking at, which are blood platelets. And those cells bind to damaged blood cells.

PUTRINO: First, we spin this down at 3,000 revolutions per minute. So right now, I have my pipette, and I'm going to put just three microliters of my sample onto a slide.

KWONG: Oh, OK. So they're looking for both microclots and platelets as a sign that something's up with the blood. What is David seeing in these samples he's preparing?

OZA: Well, all of their long-COVID patients have some of these microclots, which they don't see very often in people who have fully recovered from COVID or never had it at all, though there is some variability with the size and number of these clots, as well as how many of these people's platelets are hyperactive, which is a sign that they aren't functioning correctly after infection.

PUTRINO: Is it worse to have fewer larger microclots or many smaller microclots? Does the shape make a big difference? It probably does, but those are things that we just need to learn through the course of this study.

KWONG: So today on the show - what these microclots tell us about long COVID.

OZA: And can it lead us to potential treatments?

KWONG: You're listening to SHORT WAVE, the science podcast from NPR.


KWONG: OK. So, Anil, you and Margaret visited a lab in New York that is part of a whole research effort by a group of folks working on microclots and their potential connection to long COVID. Who else is even working on this research?

OZA: Yeah. So I wanted to talk to one of the OG researchers who sparked all this work back in 2005, and that meant a call to South Africa.

KWONG: Nice.

OZA: This is Resia Pretorius. She's a professor at Stellenbosch University.

RESIA PRETORIUS: I have been looking at blood clotting and how inflammatory markers in circulation can affect blood clotting in various inflammatory diseases.

OZA: You may remember, Emily, if you jump into a little time machine back in 2020, we were really thinking of COVID as a respiratory disease.

KWONG: Yeah. COVID was all about the lungs.

OZA: Right. But while everyone was looking at the lungs, Resia and her collaborators were seeing these microclots, first, in a few patients. But this could be true of those estimated 200 million people that have long COVID.

PRETORIUS: We quite early on felt that it really wasn't a lung disease in the true sense as we know it. It starts off as a lung disease, but it doesn't really affect the lungs as much as everyone was thinking. And when - the first sample that I received, I thought, you know, here's something not as I have seen anything in the past.

KWONG: Wow. So she was on this from the beginning because of her background. What was Resia seeing in those early long-COVID patients? What does severe clotting pathology look like, even?

OZA: So to understand what's going on in the blood of long-COVID patients, I think it makes sense to start with acute COVID.


OZA: What happens when people first get it? And Resia explains that this virus can trigger a cascade of reactions in your body.

PRETORIUS: So the spike protein has the capability to change your soluble clotting protein to insoluble little microclots. And that's where everything starts.

OZA: And these clots can be a hallmark of a whole bunch of different issues in your blood and your blood vessels.

PRETORIUS: So when you have acute COVID, you will have activated platelets, you will have vascular damage, endothelial damage, and you will have a microclot presence in some individuals after you recover.

OZA: And most people recover just fine.

PRETORIUS: After you recover, your coagulation system will reset itself, your ways of your body to cope with microclots will kick in, and you will break them down.

OZA: But for some people, that just isn't the case. Everything doesn't go back to normal. And she says these clots sort of just stick around, gumming up your smallest blood vessels, which makes it hard for your internal organs to get the oxygen they really need to function, which could explain all of these wide-ranging symptoms we're seeing with long COVID.

PRETORIUS: And when these microclots are being constantly in your circulation, your platelets are constantly hyper activated. It's in every organ. It's in every part of your body. Someone might be complaining of muscle and joint pains. The other one might be complaining of heart palpitations. Someone else might be complaining of severe fatigue, brain fog.

KWONG: Yeah. These microclots - they sound, like, very serious. And they set off a chain of events that are really bad for your body and, yeah, lead to the kinds of symptoms that we know as long COVID.

OZA: Right. And after hearing all of this, I was really interested to know what these things look like under a microscope. Do you have any guesses?

KWONG: Angry, red bubbles of pain.

OZA: Yeah. So they asked Marge and I this when we were there, and my first guess was that they were just, like, little, tiny, little circles.

Like a little ball.


OZA: Yeah.

UNIDENTIFIED PERSON: OK. Not a bad guess. Well, let's see.

OZA: Or, like, those little splotches that they do, like, a psychology test.


UNIDENTIFIED PERSON: Oh, like a Rorschach.

OZA: Yeah.

CIRINO: I don't know. I'm just envisioning, like, a white oval.

OZA: We stepped into this pitch-black room with a computer screen and this big microscope as Wade sat down and fished around for those clots.


OZA: Whoa.

UNIDENTIFIED PERSON: Sometimes we get very long and sinuous clots that look like rope almost. Sometimes we get very big circles, or sometimes it's like this. It almost looks like protruding arms that come off...

KWONG: Yeah. They sound kind of horrible, these clots. But among the patients where they're appearing and the platelets that result from the microclots, is that a sign that these folks have long COVID? Are platelets a true biomarker?

OZA: Yeah. So remember that David earlier said that all of his patients had these microclots when they looked into them.

KWONG: Right.

OZA: And seeing something in all of a certain group is pretty rare anywhere in medicine. So I asked him what he made of that.

PUTRINO: It's important to show that we're seeing a biomarker here. I think we always need to proceed with some caution because what we're seeing right now is that folks with long COVID have microclots. Healthy controls tend to not have microclots.

OZA: And there's still a lot to learn and a lot of other hypotheses about what's behind long COVID that could figure into this explanation.

KWONG: Interesting. OK. So, Anil, our colleagues at NPR have reported on research into long COVID and things like autoimmune reactions or virus populations lingering in the body.

OZA: Right.

KWONG: But what was it about the microclot research that caught your attention?

OZA: So the thing that caught my eye about this research was I didn't see it - initially, at least - in a paper or a press release or a grant application or anything like that, it was a GoFundMe page. Like, this research is being crowdfunded by patients and researchers and clinicians.

KWONG: Get out. Why is that? It seems like it's pretty relevant.

OZA: Yeah. I asked Resia about this, and she says that the pandemic was just developing too fast, and we really needed this research quickly.

PRETORIUS: So a grant application can take - usually not - if it's a year, that's fast. Sometimes it can take longer.

KWONG: I hear that.

OZA: Right. And many long-COVID patients have really, really serious, sometimes debilitating symptoms. And so there's a sense of urgency to find answers really quickly.

KWONG: So when Resia went to raise the money, what happened?

OZA: She says that people really turned out for her. And they were able to raise $161,000.

KWONG: And how was that money used?

OZA: Yeah. So when Resia was initially testing for those microclots, she was using a fluorescent microscope, the type of thing that Margaret and I saw in the lab.


OZA: And it's something that a lot of labs would have, but not so many hospitals. And so she's using that money to buy something called a flow cytometer. And that's something that a lot more hospitals would have. And if they find that these microclots are a good test for long COVID, they could roll this out in a lot more places.

PRETORIUS: Usually, it takes, also, much longer to get crowdfunding for instruments. But we got it in no time. And if it wasn't for the desperate nature of the disease, I think we would not have been able to crowdfund in such a short time.

KWONG: Yeah. I mean, it has been a dire three years. With millions of people potentially affected, we still don't really understand how long COVID even works.

OZA: Yeah. And I wanted to understand what three years with this disease looks like.

KWONG: Oh, yeah.

OZA: So I talked to Hannah Davis. She's a co-founder and lead researcher of the Patient-Led Research Collaborative. She's had long COVID since March of 2020. And she was actually on the show in June of 2020 to talk about her symptoms.

KWONG: Right. I remember Hannah. The Atlantic's Ed Yong brought on her story, and I think we talked to her. How is she doing now?

OZA: So she still has long COVID. And she says that it presents mostly with neurological and immunological symptoms. So she has trouble remembering things and other things like that.

HANNAH DAVIS: There's this urgency. You know, most of the first wavers just passed the three-year mark. And that's a really, really long time to be suffering with this illness, which in many cases has a quality of life that is just so, so low, like unfathomably low to most people - definitely unfathomably low to me, you know, not having known about post-viral illness beforehand.

KWONG: Yeah. Does Hannah have these microclots and the resulting platelets?

OZA: Yeah, she does. She was actually tested for them by David Putrino, who we talked to earlier.


OZA: And she says she feels really lucky to have even had access to this test, even though she knows from other tests and doctors that she has long COVID. And Hannah says something this important shouldn't have fallen to something like crowdfunding.

DAVIS: I mean, it shouldn't have to be like this, right? Like, it should be the case that millions of dollars are designated for finding a biomarker or identifying and creating a test or both.

KWONG: Anil, what is next for this work? And is it likely to actually change how we diagnose and eventually treat long COVID?

OZA: Yeah. So when I asked researchers what's next, they said it was two main things. First, they want to make sure that this microclot that they're seeing is a consistent signal that they are continually seeing in patients.

KWONG: Yeah, so is it a real, real biomarker in all the ways?

OZA: Right. Exactly. And then if the answer to that is yes, the second step is expanding this testing as much as they can. Hannah and the researchers that we were talking to say they want to make this testing available if they find that these microclots are pretty consistent across long-COVID patients. And Hannah knew that she had long COVID before she got tested. But it'll be really, really important for those people that have these really serious symptoms and don't know if it's because of long COVID and their doctors don't know how to diagnose it or don't know what to do with them.


KWONG: Anil, thank you so much for coming on this show, reporting on long COVID and where some of the research is at with it.

OZA: Emily, thank you for having me on.

KWONG: We will have some pictures of those microclots that Anil and Margaret saw under a microscope at our website, npr.org/shortwave.

This episode was produced by Margaret Cirino and Berly McCoy. It was edited by Gabriel Spitzer and our managing producer, Rebecca Ramirez. And it was fact-checked by me, Rebecca and Berly. The audio engineer was Robert Rodriguez. Beth Donovan is our senior director of programming. And Anya Grundmann is our senior vice president of programming. I'm Emily Kwong. See you next time on SHORT WAVE from NPR.


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