SCOTT SIMON, HOST:
The mystery of long COVID has sent scientists on a meandering journey through all manner of organs and systems in the body. Their hope is to root out what is at the core of this wide-ranging illness that emerges in the aftermath of an infection. And this week, researchers dedicated to long COVID met in Santa Fe, N.M., to compare notes. NPR's Will Stone was at the conference and joins us now. Will, thanks so much for being with us.
WILL STONE, BYLINE: Happy to be here, Scott.
SIMON: First, help us understand, what do we know or think we do about long COVID?
STONE: Yeah, we are deep into the detective work right now, trying to suss out what's driving the illness. Scientists have a lot of data describing the symptoms, how long they last, how common it is, although even that is not entirely settled. But the most cutting-edge work is happening in labs where scientists are combing through the immune system, performing sophisticated tests on blood and tissue, looking at animal models, all of this to identify what's different, what's abnormal in long COVID patients and whether that could explain their symptoms.
SIMON: Any leads?
STONE: You bet. Scientists have a handful of explanations for what could be driving the disease, but they haven't yet made that final link where they can say, OK, this is what's responsible. And just to be clear, there are probably multiple drivers of the illness because the term long COVID itself is kind of a catchall for what are a number of different syndromes. So it's in this area where some of the most interesting work is happening.
SIMON: Well, what did you hear in Santa Fe?
STONE: Well, one thing that got a lot of attention was emerging evidence about differences between males and females when it comes to long COVID. So the context here, Scott, is that males tend to do worse with acute COVID-19, but females seem more likely to develop long COVID. And researchers are now finding there are certain signatures in the immune system of females with long COVID. Akiko Iwasaki at Yale University is leading some of this research.
AKIKO IWASAKI: We're already starting to see sex differences in long COVID symptoms, as well as, you know, potentially, like, maybe the autoimmunity more associated with female patients.
STONE: Iwasaki's lab has actually found that females are more likely to have evidence that a herpes virus called Epstein-Barr virus, which is what causes mono, is being reactivated. They are also more likely to have activation of certain immune cells called T cells.
SIMON: So where does that all lead us?
STONE: Hopefully it's one way to separate out long COVID into different groups and then eventually target that with treatment. Just one more point on these sex differences - at the conference, Iwasaki's lab also shared some unpublished data showing that testosterone levels were lower in female long COVID patients compared to their controls who don't have symptoms. Julio Silva is an MD/Ph.D. student at Yale who worked on this, and he says having less testosterone was associated with a certain immune profile and worse symptoms.
JULIO SILVA: Part of the reason we started looking at testosterone and so forth is because some of these patients, including trans individuals who were telling us while on testosterone therapy, their symptoms had improved dramatically - this really led us to try to understand how, you know, these hormones are interplaying with the immune system.
STONE: Now, I want to be really clear - that's anecdotal. The testosterone evidence is preliminary. It needs to be replicated, but it is intriguing.
SIMON: Will, what else struck you from the conference?
STONE: Yeah, there's also some fascinating work on this theory of viral persistence. And basically there's evidence that at least parts of the virus, like the spike protein, are hanging out in some long COVID patients. Scientists think that could be driving the disease, although they don't know that yet. Dr. Timothy Henrich at the University of California, San Francisco, is using a special kind of imaging to trace the immune response, specifically these T cells, which we mentioned before, and where those are being activated.
TIMOTHY HENRICH: We saw some very unexpected findings - increases in the spinal cord and the brain stem, for example, which, you know, we really shouldn't have activated T cells in the spinal cord or the brain stem. We also saw it in the gut wall. We saw it in the lung tissue.
STONE: Now, what does this mean? We don't really know yet. It could be the immune system is trying to get rid of these residual viral reservoirs. Maybe it's the immune system has just gone awry, maybe autoimmunity. So clearly, still many more questions than answers, but lots of promising leads.
SIMON: NPR's Will Stone, thanks so much.
STONE: Thank you. Transcript provided by NPR, Copyright NPR.
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