Does the risk of getting long Covid increase each time you get reinfected?

More than three years into the coronavirus pandemic, fewer and fewer people are experiencing their first Covid-19 infections. But as cases climb, those who’ve had the virus before may wonder: What are their chances of developing long Covid — and does the risk increase with each reinfection?

Fatigue and brain fog may be the first post-infection symptoms that come to mind for long Covid, but lists compiled by the Centers for Disease Control and Prevention and by the World Health Organization also include musculoskeletal pain, shortness of breath, gastrointestinal disorders, and dysautonomia, the disruptions in heart rate, blood pressure, sweating, and other functions our bodies carry out without our control. We still can’t predict, prevent, or cure long Covid — or understand why it affects some people and not others.

There is, however, a lot of research underway exploring the many still-unanswered questions about long Covid. Ziyad Al-Aly, chief of research at the VA St. Louis Healthcare System and clinical epidemiologist at Washington University in St. Louis, talked with STAT about what we understand about long Covid so far, and what scientists are still trying to figure out. (One of his studies, for example, showed that vaccination appears to lower, but not eliminate, the risk of long Covid.)

This interview has been edited and condensed for clarity.

Let’s set the stage: What did you learn about Covid reinfection in your study based on the U.S. Department of Veterans Affairs’ national health care database?

We compared people who have a reinfection to people who have no reinfection — not comparing the severity of infection versus the first. What we found is really undeniable: It’s very clear in our data that reinfection contributes additional risk of long Covid.

What does that mean for patients? 

If you’ve had Covid previously and dodged a bullet and did not get long Covid the first time around and you’re getting another infection now, you’re pretty much trying your luck again. People need to understand that you can get long Covid the second time, even if you dodged the bullet the first time. You can get long Covid the third time.

What if you already have long Covid?

If you had long Covid before, upon reinfection there is a risk of worsening problems. You may have had brain fog and fatigue but not dysautonomia or other manifestations. Long Covid is a broad basket of conditions. Even if you’ve had it before, you’re also trying your luck again.

So each time you are infected with Covid, you are rolling the dice on long Covid, whether it’s a first infection or second or third or so on?

That’s correct.

Does that risk add up, or does each roll of the dice stand alone? 

This is really hard to answer. I can give you my speculation: There are two opposing forces at play here. It could be that prior infection may have primed the immune system in a way resulting in subclinical damage that people are not even aware that they have. The second infection sort of surfaces it and makes it more clinically evident and diagnosable, and they start feeling fatigue and brain fog and all of that.

In the other, opposing pathway, the immune system has seen this virus before on the first infection in a particular individual, and when they get a second infection, the immune system would say, “I’ve seen this virus before. I know how to deal with it, I’m going to clear it better” and they may have actually even milder disease.

This is why long Covid is so complex: These two things can happen in different directions.

Do people get over long Covid?

Anecdotally, from the clinics we know that some people come back and say, “I feel better” or “I feel I improved.” If you dig a little bit deeper, they did not get back to their baseline; they adjusted their baseline. They used to be able to walk the dog three blocks out of the house and now they only do a half a block. Or they used to garden Saturday or Sunday and now they feel exhausted just watering.

Recovery, unfortunately — for fatigue and dysautonomia and all that — is actually quite rare. 

Where should research be focusing?

Long Covid does not seem to be self-resolving, in the sense of spontaneous recovery or recovery in the absence of a cure or a treatment that’s been validated. It further raises the importance of finding treatment because this is not going to go away.