There’s no way to diagnose long COVID right now. New TGen research could give us a blood test

Millions of people around the world suffer from long COVID. But, there’s no way to actually diagnose it, other than assuming patients displaying symptoms have it.

Scientists, though, believe they may have found a way to figure out if a patient suffering from long COVID symptoms actually has the ailment. Researchers at the Translational Genomics Research Institute, or TGen, along with colleagues in California, say they’ve identified a potential biomarker that could serve as a diagnosis.

Dr. Patrick Pirrotte, associate professor at TGen, is a co-senior author on the study and joined The Show.

Full conversation

MARK BRODIE: What exactly is this biomarker that you’ve discovered?

DR. PATRICK PIRROTTE: Yeah, this biomarker is essentially a protein fragment from a viral protein, so that belongs to the SARS-COV-2 or COVID virus, and, this viral protein is a, is a so-called replicate, and we identified it in vesicles that are secreted by patients that suffer from long COVID.

BRODIE: And so you found this in their blood, but it sounds like interestingly not every time you took a patient’s blood. Am I right that sometimes you found it and sometimes you didn’t?

PIRROTTE: So our initial goal was not to look for COVID-specific proteins in blood. We were interested in assessing the effect of a very mild exercise regimen on improving symptoms of long COVID. And we did observe improvements of the symptoms, so the study itself was successful.

But we really wanted to also investigate what was happening in terms of proteins that were changing during that exercise regimen, and if we could actually tie these proteins to these physiological improvements that we had observed. And then this led to a further study where we actually looked for viral proteins being in circulation.

And it is correct that we didn’t see these viral proteins actually in at every time point in our study, so we collected essentially plasma from participants, and we followed a number of different proteins over time, and sometimes you would see these viral proteins come up, and sometimes they would not be present.

And we believe this is related to both the really low abundance of those proteins in blood, and so part of it is just the sensitivity of our methods. And it’s also probably related to the fact that participants don’t always shed viral proteins.

Even if long COVID patients are potentially harboring a viral infection, they’re not specifically infectious all the time. They’re not necessarily producing proteins, and so those proteins don’t always show up in blood.

BRODIE: Did you find any kind of relationship between the number of times that you found the protein in a particular patient and the severity of the long COVID symptoms that that patient exhibited?

PIRROTTE: So our study was a pilot study in 14 participants that we followed over three months. We suspect that that is the case, but we haven’t, we’re just not powered yet to make that claim. But we do suspect that that’s the case.

TGen

BRODIE: OK. So what to you is the significance of this? I mean, you mentioned, for example, that you know, you were, you’re studying patients who had long COVID symptoms and that’s really the only way that anybody knows they have it, right? Right now they have symptoms.

So what would be the significance of actually having maybe a way to say, “Yes, you have it,” or “No, you don’t”?

PIRROTTE: Yeah, today there is no molecular test that accurately helps diagnose patients with long COVID. So long COVID symptoms are usually generalized fatigue, shortness of breath — so we call that dyspnea — or exercise intolerance and also brain fog — so the inability to focus or concentrate or, or just general sluggishness. And those can really persist for months or sometimes even years after a COVID infection.

Those are all physiological symptoms, but they’re not necessarily molecular symptoms. So we don’t really have a blood test today that can allow us to do that. And I think this study here provides really, I think a new way of, of looking at diagnosis of patients with long COVID.

And we would like to pursue really the development of potentially a test that would allow us to identify COVID patients.

So we do identify certain signatures of those viral proteins, not just specifically in blood, but in what we call extracellular vesicles. And extracellular vesicles are little bubbles, if you want, that packaged material from all of our cells, and usually those vesicles are secreted by cells, and they use cells use that to, to communicate with each other. But if those cells are infected with the virus, well, they will potentially also contain viral proteins. So those vesicles can carry proteins, genetic material and other signals.

And I think the idea that we can isolate then those vesicles and tap into what’s happening into individual cells just by simple blood draw makes this very attractive as a diagnostic approach.

BRODIE: Is it possible that any of that might help lead to a treatment for long COVID?

PIRROTTE: Yeah, absolutely. During the course of their infection, patients with long COVID seem to harbor viral particles in their cells, but they’re not necessarily producing proteins and secreting the actual virus. And this is what we call a reservoir or COVID reservoir, where essentially the virus is dormant and hidden in our body. And only during some specific time frame will this virus, for instance, produce viral particles that will be infectious.

And I think the fact that we’re able to measure these viruses as cargo in those extracellular vesicles in blood actually tells us that the life cycle of the virus is actually pretty complex, and it doesn’t always stay hidden. And I think that’s probably a good time point when we can hit it with a certain therapeutic regimen.

We do have a regimen of therapeutics available to us today. So I think understanding better that maybe those patients should be treated, continuously treated with effective drugs at the time where they’re actually secreting those viral particles, may be the way to go.

BRODIE: I was going to ask you about that because obviously there are treatments that some patients get. It sounds like it’s your expectation that at least for some number of patients, those treatments, those existing treatments will continue to be effective.

PIRROTTE: They will most likely continue to be effective, but viruses are really good at evading our common therapy, so I would expect that COVID or SARS-COV2 will also adapt and find ways to potentially remain hidden in some of our cells.

And so I think targeting those cells and generating or developing targeted therapies for those patient populations that suffer from long COVID, where the virus has potentially adapted to remain hidden, will be necessary.