The cause of long COVID, where patients experience symptoms months after their initial illness, is a mystery. Now, a new study might bring scientists a step closer toward understanding the disease.
A pulmonologist from Albany Medical Center finds in a new study that Long COVID appears to be a single disease and not an aggregation of multiple conditions.
Study author Dr. Ariel Jaitovich says additional, wider studies are needed, but the findings could lead to better diagnoses of Long COVID, gauging its severity, and aiding in treatment.
The study was published in this month’s issue of the peer-review eBioMedicine journal. WAMC’s Lucas Willard spoke with Dr. Jaitovich about his research:
The symptoms of acute COVID are not generally the symptoms of long COVID. Patients with acute COVID develop a flu-like condition with fevers and muscle and joint pains. It could be cough, shortness of breath, mainly something like a flu-like condition. That has nothing to do with long COVID. Long COVID is as if the patient has been drained out of energy. So, there is no capacity for the patient to execute their activities, their normal activities, including thinking or breathing or moving, because they feel that they run out of batteries.
Has it been until now, perhaps, unclear about what exactly caused long COVID? Were there ideas about there could be other diseases in the body or other infections? Could the immune system be weakened and the body is affected by other things? Has it essentially been unclear about what's caused long COVID?
So, for full disclosure, it is still unclear what causes long COVID. I don't think that I am in a position to say that I found a final answer, whatsoever. But, like you said, there are many ideas that had been postulated as of why long COVID occurs, including the remaining existence of a virus that was not fully eliminated by the body and remains in a very, kind of, undetectable range, yet present. Also, there is an idea that the virus caused a certain insult to the body, to which the body overreacted and built up, kind of, an overdrive, low intensity immune dysregulation, leading to those conditions, and many others. One of the limitations of the research conducted is that it has been mainly focused on symptom-specific. So, for example, there are some ideas of what could be causing shortness of breath or what could be causing muscle weakness, but not something that is a universal signature of long COVID. And that is a very significant limitation, because in the medical conversation, there is this idea that is floating around that is, ‘Well, yes, acute COVID is one disease, and then that disease leads to complications or some kind of lingering issues that are very diverse and somewhat disconnected from each other.’ Similarly, for example, to the post critical illness syndrome. So, a patient goes to the ICU because it's very sick and survives the hospitalization. The patient can develop skin pressure sores. It can develop kidney failure, it can develop cognitive dysfunction. It can develop muscle weakness. And it is kind of considered that those entities are triggered by the initial ICU admission, but they are disconnected from each other. That was kind of the feeling that dominated the conversation in long COVID, that those all those things were kind of an aggregation, an artificial aggregation, of things that were disconnected from each other in the first place. We think differently. We kind of challenged that idea. We think that if you dig deep enough, you will be able to find a common foundation of long COVID, and that is the basis of our of our research.
So, your research shows that long COVID appears to be a single disease?
Correct.
But what about the COVID virus allows it to linger in the body and cause such a wide variety of conditions?
It is possible. But if you try to detect the virus, the viral particles, or surrogates of the viral presence in the body in patients with long COVID, most of the times, you will fail to do so. So it is, I think it's going to be very difficult to substantiate the idea that the virus remains in the body as as a consequence, long COVID exists. It seems to me that there is something like a footprint left by COVID originally present in the body, and that footprint remains as a lingering abnormality that takes a long time to normalize.
So, your study shows that different patients who've experienced long COVID essentially share this same footprint. Is that correct?
That is correct.
Can you tell me about what that footprint actually is, right and how you can sort of explain it to someone who's not a COVID doctor? (laughs)
Right, absolutely. So let me tell you a very common example that we give.
Sure.
So, the information of the of the body, all the information that leads to the body, human body, as it is, is present in certain letters that are written in the DNA. That is the way the information is held by your body. However, the DNA is not a linear kind of line, or a linear change. Is something that is, you know, packed together in a very convoluted way. So, if the information is in the DNA, but is really in the center of a tangle, it will not be really visible or accessible, because it's packed, you know, in a center of something that is very complex.
So, you're looking for very small changes in DNA, which has a lot of information. So, is it looking for a needle in a haystack kind of a thing?
Absolutely, absolutely. But the important thing is that, imagine that you own the library of the world, and you were able to say, ‘I have all the information of all the books in the world,’ but in order to access a certain type of information, you need a ladder, because you wouldn't be able to find, you know, the top shelf, where some books are located. So, the information is not…what defines what the body can read, and what the what kind of information the body can have, is not only the number of books, but also the accessibility to a certain type of books. So, we investigate chemical modifications to the DNA that are not specifically on the information that the DNA has, but on changes, chemical changes associated with the DNA that define how the DNA becomes accessible. That is a phenomenon that happens due to chemical changes to the DNA, and is broadly known as an epigenetic change. So, it's not a change in the genetic information, but it's a change associated with the genetic information that decides or influences the way the genetic information can be appreciated by the body.
OK. So, is that possible, then, to look for that footprint through a simple blood test? Can you find if certain individuals may be more at risk for developing long COVID, even, maybe, before those symptoms emerge, or maybe even before they become infected by the virus in the first place?
It's a very good question that you're asking, because we do not have information as of what was the status of the patient with long COVID before the patient developed COVID, because this is the nature of the research we conduct. We don't, we cannot access a healthy person and wait for that person to become sick. It's impossible. So, you essentially enroll a patient who is complaining about the disease. So, coming to your specific point, we don't know if those changes that we are seeing in long COVID individuals are the novel, or new changes induced by the virus, or were pre-existing conditions that the patient had before the infection, and represented the susceptibility for the patient to become infected and eventually to develop long COVID. And that cannot be done with human studies. Is not really possible because you don't have, you don't have control of this pre -existent status of the patient.
But now that we've identified, or that you and your team have identified, this footprint, does that open a door, open a window, towards finding a treatment, potentially?
We don't know, because what we found is an association between a symptom, or a constellation of symptoms, and a chemical signature in those epigenetic changes in the DNA. But two things that are associated are not necessarily cause, consequence related. So, the fact that those changes occur in patients with long COVID doesn't mean that if you were able to be capable of reversing those changes, you would necessarily lead to an improvement of the symptoms, but it's a first step to at least define a biological underpinning. Because remember, like I said before, one of the challenges is that we find with those patients, is that the symptoms they have do not correlate with any organic, identifiable abnormality using the tools that the medical field has to investigate the lungs or the brains or the muscles. So at least, I feel that by finding some biological underpin, some objective entity in the circulating blood that can define a patient who has and discriminate that patient from a patient who doesn't have long COVID, is a very important first step to investigate, for example, the trajectory of those symptoms. Do those changes improve in association with the improvement of the symptoms? That is the next big question that we want, are these change in the symptoms are also going to correlate with the changes in these DNA methylation abnormalities in the blood? And things like that.
