Science Friday - What We Know After 4 Years Of COVID-19

Episode Date: March 20, 2024

Four years ago this week, the world as we know it changed. Schools shut down, offices shuttered, and we hunkered down at home with our Purell and canned foods, trying to stay safe from a novel, deadly coronavirus. Back then most of us couldn’t fathom just how long the pandemic would stretch on.And now four years later, some 1.2 million people have died in the U.S alone and nearly 7 million have been hospitalized as a result of a COVID-19 infection, according to the CDC.So, what have we learned about how COVID-19 attacks the body? What can be done for long COVID sufferers? And what can we expect in the future?Ira analyzes this era of the pandemic with Hannah Davis, co-founder of the Patient-Led Research Collaborative in New York City, and Dr. Akiko Iwasaki, immunobiologist at Yale Medical School in New Haven, Connecticut.Transcripts for each segment will be available the week after the show airs on sciencefriday.com Subscribe to this podcast. Plus, to stay updated on all things science, sign up for Science Friday's newsletters.

This month marks four years since the beginning of the COVID pandemic. So where do we stand now? The pandemic is not over until there is meaningful treatments and a cure for long COVID. It's Wednesday, March 20th, and you're listening to Science Friday. I'm sci-fi producer Rasha Auretti. Four years ago this month, the world as we know it, changed. Schools shut down, offices shuttered, and we hunkered down at home, armed with our Purell and canned foods, trying to stay safe from a novel deadly virus, COVID-19.

Back then, most of us couldn't fathom just how long the pandemic would stretch on. Here's Ira Flato. And now four years later, some 1.2 million people have died in the U.S. Nearly 7 million have been hospitalized here as a result of COVID. There are plenty of people with long COVID, the COVID that keeps on giving. So what have we learned? about how COVID attacks the body. What can be done for long COVID sufferers? And what can we expect in the future? Joining me to talk about all of this is Hannah Davis, co-founder of the patient-led

research collaborative in New York, and Dr. Akiko Iwasaki, immunologist at Yale Medical School in New Haven, Connecticut. Welcome back to Science Friday. Thank you so much. Thank you for having back. Nice to have you. Well, at this point, hospital emergency rooms are not over flowing. Vaccinations are there. Deaths are way down. The CDC says COVID quote is no longer the emergency it once was. But Hannah, long COVID is still very real. And as a long haul, you're not very happy about the situation, are you? Absolutely not. Long COVID is a really severe multisystemic illness that has serious consequences on the daily lives of sufferers and their families. It has incredibly serious economic consequences.

It has really tremendous impacts on, you know, children who get it. It happens to all ages. And it just completely disrupts your quality of life. We're talking about things like damage to blood vessels, damage to the immune system, cognitive impairment and memory loss, even in young people. And we are not seeing an effort to adequately. research and treat this at the scale that the federal government needs to be providing. Dr. Iwasaki, as I say, the CDC says that COVID is no longer the emergency it once was.

It has shortened its isolation guidelines. It's ending its free test program. What do you make of all this? Yeah, I don't quite agree with that measure myself. We know, as Hannah said, there are millions of people. suffering from long COVID. And the shortening of the suggested isolation period and lack of testing provision will make the virus, you know, even more easily transmitted. People won't know they're infected. They're probably not going to even test anymore, which just makes this situation

worse because, you know, more people will be unknowingly become infected and develop long COVID. So I am concerned about this sort of lifting of all measures. Hennie, is it true that long COVID rates are going down? No, that is a narrative that has been perpetuated, I think, in order to kind of help communicate that the pandemic is over when it's not. The CDC and census have a household pulse survey that actually just released new data and showed that the rates of long COVID in the U.S. adult population have actually jumped tremendously since the last time they counted. We're now up to 6.8% of all U.S. adults have long COVID currently in the United States. That's one in 15 people, basically on the same rate as diabetes. There have been many, many cases of long COVID after Omacron. You can still get long COVID despite

being fully vaccinated. And even if you have prior infections, more evidence is coming out showing that reinfections are actually a risk factor for long COVID. So the narrative that long COVID is decreasing is just objectively wrong. And you know, that's what bothers me about the attitude is that people are so cavalier about this, thinking, you know, I can get COVID and I'll, I'll get past it like I got it the first time. But they don't realize they can get long COVID, do they? I mean, I'm out there still wearing my mask in crowds because I'm still fearful that maybe I will recover from a COVID infection, but it might turn into a long COVID one. Absolutely. There's no reason to assume that your response to COVID is going to be the same every time. And definitely these

days, the people who are getting long COVID in the last year or two are people who recovered completely fine from their first infection or even their second infection and only got it on their third or fourth reinfection. Wow. Akiko, are we getting closer to understanding what's driving long COVID? You know, are there any running hypotheses? Oh, yes, absolutely. We have several hypotheses that we think are the root causes of long COVID, you know, one of them being persistent virus replication. And there's been multiple reports, over 100 reports showing that the virus antigen and RNA are present in various tissues months and years after the initial infection. There's also the idea.

idea of autoimmunity that's driving the disease, as well as dysbiosis of microbiome, reactivation of herpes viruses, and tissue damage and inflammation, and many others. But we are getting evidence for many of these root cause hypotheses, and, you know, what we need now is to understand how many endotypes, these are different subsets of diseases that are driven by different causes are there for long COVID and how do we diagnose and treat each of these endotypes? You know, scientists have been trying to untangle how COVID affects the heart, the brain, the lungs we've heard about these. I was surprised to read, Hannah, that it can also affect the mitochondria. Tell me about this. Yes, absolutely. There have been a couple of studies showing that actually like some

other post-firal illnesses that there's mitochondrial dysfunction, like loss of the mitochondrial membrane potential. There was a recent study out in January from a team in Amsterdam looking at this symptom called post-exertional malaise, which is actually a really interesting and very specific symptom where there's kind of a disproportionate immune reaction, flu-like symptoms, extreme muscle pain and just this feeling kind of of not getting enough oxygen after a disproportionate amount of exertion. For example, you set your bed, then you're in bed for two or three days, or you do your laundry, and you just can't get out of bed for the rest of the week. It's a very, very severe symptom, but they also found mitochondrial issues in patients that had post-exertional malaise. Well, speaking of

exertion, does that mean that exercise can actually hurt long COVID patients? Yes, exactly. The same study actually found tissue necrosis and amyloid plaques in the tissue of patients who had exercised. And this has been something that patients have been saying for years and years and years. And because post-viral issues haven't been taught in med school and because exercise is kind of always seen as this treatment for everything, but it just took a while for the idea of exercise as harm to be taken seriously. And so it's great that we're now starting to see research that confirms the patient experience. And Akiko, I understand that you have a new research paper that's a pre-print about sex hormones and long COVID. What have you found there?

So this new study is based on data that Dr. David Petrino at Mount Sinai, and the Yale team have worked on together. In last fall, we published a paper showing that there are distinguishing signatures in immune profiles of people with long COVID. And this time, what we did was to take that data set and analyze a females and male patient separately. And that enabled us to discover new things, such as the low levels of testosterone being correlating in women with long COVID, and that testosterone levels are negative predictor of long COVID status in

women. And conversely, we find that estradial levels are a top negative predictive hormone in males with long COVID. So this study really illustrates the importance of sex hormones in regulating disease process. Could it help in treating the disease? Yeah, so that that would be the next step is to see whether treatment with hormone therapy would be beneficial. Now there's a lot of, you know, careful studies that have to be done between now and being able to say that. But this study provides a platform or a basis to start thinking about these kinds of therapies. Let's talk about treatments for a moment. Are there any clinical trials for long COVID treatments?

Vincent, are you excited about any of them? So we are almost done recruiting for our Yale Paxlovod trial. So this is a trial in which we have randomized people into placebo arm and a treatment arm in which 15-day course of Paxlovit is giving to those with long COVID. And so we are monitoring symptoms before, during, and after, as well as looking at biological markers in people. And what we're trying to achieve in this trial is to see, you know, what proportion of people taking Paxlovit benefit from this treatment.

And in those people who benefit, what are the biomarkers? And that will help us understand empirically what biomarkers are associated with improvement with Paxlovit and potentially being able to recruit people with those biomarkers. in future studies. That's interesting. Hannah, several COVID researchers have called for a moonshot, a giant infusion of cash to study long COVID. How much are they asking for? Yes, the long COVID moot was put forward in part by my colleague at Patient-led Research Collaborative Lisa McCorkle, and the moonshot's calling for $1 billion a year for 10 years. And this sustained investment is really important for a few reasons. I mean, the first is that no illness has ever been solved with a one-time

infusion, which is what long COVID has right now, but also that new researchers and researchers who are turning to the field from other fields like HIV and other infectious associated illnesses need to be shown that this is something to invest in and that they can invest their careers in. And we really need to see a huge collaborative effort to be able to solve this thing on any type of quick timeline. Akika, what do you think? Good idea? I think it's an excellent idea. As Hannah says, as researchers, we need to know that there's continued investment in research to be able to even start to engage in something. So for young investigators thinking about future research areas, you know, if there's infusion of one-time funds for a disease, that's not an attractive area to go into because there's no future funding.

But if it is a commitment for 10 years, that gives people the security to tackle complex diseases like long COVID. Hannah, what are people with long COVID feel? Do they feel like they have been ignored, left out, shoved to the side? No one thinks about them anymore? I think long COVID suffers right now have been put in a terrible position where they have been sacrificed almost and forced to live in the state of ongoing cognitive dissonance and dismissal from providers, dismissal from their family and loved ones, and, you know, being removed from society. That's not an over-exaggeration. That's literal in order to pretend to the rest of the world that,

this illness has improved that it's not happening anymore, etc. Like the cost of getting back to quote unquote normal is coming at the health and inclusion of long haulers. And it's terrible to be a part of. It really is something that just needs to change dramatically because the pandemic is not over until there is meaningful treatments. and a cure for long COVID. This is Science Friday from WNYC Studios. If you're just joining us, we're talking about four years of the COVID pandemic. You know, it's not easy to find information about long COVID.

Absolutely. And, you know, to some extent, that's intentional. We've worked a lot with the CDC over the past four years. They have a very specific narrative designed to communicate that the pandemic is over, and that COVID is not the threat it once was, and that's just objectively not true. And as people, you know, living in this research and knowing that it's the opposite, it's very hard to watch people be sacrificed to that narrative. So where can people learn more? What if people think they have a case of long COVID?

Where should they go for more information? There are several long COVID groups that are putting out information. I mean, ours, patient-led research collaborative, we have a lot of resources. We do a lot of patient prioritized research. The people's CDC does a lot of more accurate epidemiology. And yeah, just following long COVID researchers, I think would be the best thing to do. Let's talk about the next phase of this pandemic, Akiko. What are your concerns or hopes? What do you think it will look like? Yeah, I'm afraid that with less and less sort of preventative measures and of transmission, you know, this virus will continue to spread and potentially mutate further.

The variance of concern that we've seen so far, I mean, you know, the virus is selected on the basis of its ability to transmit. So we could see more future waves, especially with less isolation, less masking, less vaccination, et cetera. So COVID is certainly not over. It's going to continue. And with it comes the rise, even further rise of the number of people affected by long COVID. And it's really a devastating situation that needs more attention. Hannah, how do you give it more attention? I think there really need to be public health campaigns around recognizing some of the basic manifestations of long COVID. One of the things we know is that resting early on is really vital. and that's really just not common knowledge.

There are some conditions like pots, which is basically a form of disodinomia, where when you go from sitting to standing, your heart rate raises over 30 beats per minute. It's one of the most common manifestations of long COVID. It's something you can test for at home, but there's been absolutely no public health campaign to just inform people what it is, how to test for it, things like that. there hasn't been enough medical provider education. So, you know, your average PCP isn't going to know that there are some options to at least alleviate some of these symptoms. And yeah, really more resources to kind of communicate around some of the narratives of what we do know about long COVID. Because at

this point, four years in, it's not mysterious in the way that it's communicated. It's, it's, we know a lot about it. We know some things that can tangibly help people. And, the longer people wait to get diagnosed and get treated, the worse off they will be. Good words to end on. Hopefully people will be informed and people will get help and we'll have some more research coming. And I want to thank both of you for taking time to be with us today. Thank you so much. Thank you so much. Dr. Akiko Iosaki, immunologist at Yale Medical School in New Haven, Connecticut. Hannah Davis, co-founder of the patient-led research collaborative in New York City,

you can go to their website and learn all about long COVID. That wraps up today's show. Lots of folks help make the show happen, including... Dee Petersmith. Sandy Roberts. Beth Rami. John Dancosky. Join us tomorrow to learn about the ultimate living fossil.

Catch you then. I'm sci-fi producer Rasha Eredi.