For those with long COVID, many questions remain

“The number of referrals we’re getting has not declined,” said Dr. Jeffrey Parsonnet, who works at the Post-Acute COVID Syndrome Clinic at Dartmouth Hitchcock.

A passer-by departs Dartmouth-Hitchcock Medical Center, in Lebanon, N.H., Monday, Jan. 3, 2022.Steven Senne/Associated Press

CONCORD, N.H. -- President Joe Biden may have declared that the COVID-19 pandemic is over, but the long COVID clinic at Dartmouth Hitchcock in Lebanon, N.H., is as busy as ever. Long COVID remains a relatively mysterious disease, with doctors and researchers still trying to understand who is at risk, how to diagnose it, and how to treat it.

Dr. Jeffrey Parsonnet, an infectious disease doctor, founded the Post-Acute COVID Syndrome Clinic in April 2021 with no idea of how long the clinic would be open. Two years later, he’s still working alongside Christina Martin, a nurse practitioner, to see 70 to 80 patients a month. They spoke with the Globe about what is known about long COVID, and the questions scientists are working to answer.

This interview has been edited for length and clarity.

Q: When the clinic opened two years ago, it was unclear how long it would be needed. How do things look today?

Jeffrey Parsonnet MD, Staff Physician, Infectious Disease & Intl Health. Mark Washburn/Dartmouth Health

Parsonnet: The number of referrals we’re getting has not declined, which seems paradoxical because deaths and hospitalizations are declining. But the number of patients being referred to our clinic is pretty much holding steady despite widespread vaccination. What’s going on there?

First, if you’ve had COVID before, and get it again, you could get long COVID after the second time. Second, vaccination is really good at preventing serious illness, death, and hospitalization, but it does not prevent you from getting long COVID. Around 200 million people have had COVID now. The symptoms are very nonspecific: Anxiety, depression, fatigue, brain fog. So people are saying, “Oh, maybe it’s because I have long COVID.” We’re getting a lot of referrals for people who have these nonspecific symptoms that may not really be related to long COVID.

Can you diagnose long COVID?

Parsonnet: We try our best. We like to have documentation that a person actually had COVID. But there’s no diagnostic blood test or other kind of tests to know that a person’s symptoms are due to COVID. It’s really just experience and educated guesswork.

Obviously, the science around long COVID is evolving. Can you talk about what we know for sure at this point about it as a disease?

Parsonnet: Long COVID is basically a neurologic disease, or we could call it a neuro immunologic disease. It’s something that shows that the central nervous system -- the brain and the major nerves, spinal cord -- are somehow adversely affected and causing the symptoms. All of the symptoms stem from the brain and how it’s interpreting signals from the body

What do we know about what causes it?

Parsonnet: The answer is not very much.

There are several theories about what’s happening and it seems to be an immune disease of some kind. Some of it is the body’s reaction to the virus. One theory is the virus remains in the body in some way and continues causing an immune response that causes the symptoms. And maybe that’s just leftover pieces of virus.

There seems to be an immunologic thing going on in the brain. It could be that the blood vessels are affected. It could be that some of the cells are just not working right. But that’s sort of all we know: the brain is somehow affected and there’s probably some inflammation there.

Who are your patients?

Christina F. Martin, MSN, APRN, Infectious DiseaseMark Washburn/Dartmouth Health

Martin: The majority of patients in our clinic are women -- 70 percent to 75 percent women. We have some suspicion that maybe it’s the differences in immunology between men and women. The men were sicker with acute COVID but the women tended to present more with long COVID symptoms.

What else do we know about who is likely to develop long COVID?

Parsonnet: You have to really be careful about that because we have a lot of patients who are completely healthy -- runners, athletes -- who then get debilitating fatigue and brain fog after COVID. So it’s really hard to know.

How do you treat people experiencing the symptoms of long COVID?

Martin: The first thing is listening to their stories. Often these patients have seen multiple specialists and been told, “This is anxiety” or “You’re having a panic attack.” They start to feel doubtful about the healthcare institution. They’re not sure if you’re going to accept what they say or if you’ll prejudge them and call it mental illness. Their faces change when you’re nodding and saying, “I’ve heard this before, you’re not alone.” Even that is therapeutic for patients.

There’s no Holy Grail. Without knowing what causes long COVID, it’s hard to say “Here’s the magic treatment.” But we do know that patients can manage their fatigue through energy conservation — not over exerting themselves. We often send people to physical and occupational therapy.

If they are anxious and struggling with mental health on top of their other symptoms, they need to manage that to help lower their stress and calm the nervous system. We can help them get counselors and medication as well.

How long does it take to get better?

Parsonnet: Most patients get better over time. We still occasionally see some people who have had long COVID for two and half to three years, but most of the patients we’re seeing got COVID last year or at the end of 2021. We used to think everybody got all better, but now it’s clear that’s not the case.

Martin: A patient once said to me that they recover, but it’s glacial at times. The ones that can really figure out their fatigue and their energy tend to recover quicker than the ones with the athlete mindset: you ignore the pain, you ignore the fatigue, you push through it.

How can people protect themselves from long COVID?

Parsonnet: You can get long COVID after having been vaccinated. But vaccination prevents COVID and therefore prevents long COVID. Also, people who have been vaccinated and then get COVID are less likely to get long COVID.

Where is COVID science heading next?

Parsonnet: There are very few treatment studies, but there are some coming along.

One of the theories is that the virus is still alive in the body, which suggests treating with an antiviral drug like Paxlovid could be a benefit. Last year, there were a couple case reports of people who had long COVID and then they got COVID again so their doctor prescribed Paxlovid. Lo and behold, all their long term symptoms got better. That’s prompted several groups to plan studies.

The second is if this is mainly an immunologic process in response to the virus, drugs that suppress the immune system might be a benefit. I’m guessing that there will be studies on that.