What We Know about Long COVID—and What We Don't – Boston University

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Long COVID remains one of the pandemic’s great mysteries. Three years in, scientists still aren’t quite sure why some people get stuck with the syndrome and its cluster of debilitating symptoms long after their COVID-19 infection has cleared, while others breeze through and quickly return to a normal life. 
In part, that’s because long COVID is so hard to pin down. For some patients, the main symptom is fatigue; for others, heart and respiratory problems. Still others may have frequent headaches, trouble sleeping, loss of taste, stomach pain, rash, muscle aches, or changes in menstrual cycles—or maybe a mix of symptoms. One patient may have a few annoying complaints for a couple of weeks, a second seemingly permanent discomfort. 
There’s no simple formula for diagnosing patients, no test to tie symptoms to COVID-19, no pill to pop to make everything go away. Scientists and the public can’t even agree on what to call it: take your pick from long COVID, post-COVID conditions, long-haul COVID, post-acute COVID-19, post-acute sequelae of SARS CoV-2 infection, and chronic COVID.
Because it’s so difficult to diagnose, it’s also tough to figure out how many people have had it, but the Centers for Disease Control and Prevention suggests about 15 percent of all Americans have suffered from long COVID and that about 6 percent currently have it.
At the Boston University Chobanian & Avedisian School of Medicine and its primary teaching hospital, Boston Medical Center (BMC), researchers and clinicians are trying to decode long COVID. As well as treating patients through BMC’s ReCOVer Long COVID Clinic, they’re leading the National Institutes of Health–funded RECOVER (Research COVID to Enhance Recovery) Long COVID Study, an effort to better understand the condition and pioneer new prevention and treatment approaches.
To find out what researchers have learned since starting the study last year, The Brink spoke with Jai G. Marathe, a Chobanian & Avedisian School of Medicine assistant professor of medicine and BMC infectious diseases physician, and Fitzgerald Shepherd, a Chobanian & Avedisian assistant professor of general internal medicine and BMC hospitalist. They’re both investigators on the study.
Marathe: That a lot of people recover; it’s a matter of time. But we also have people who have had persistent symptoms since the beginning of the pandemic. It’s a whole mishmash of timelines, depending on where they are in their trajectory for recovery versus plateauing with their symptoms.
Shepherd: We’re trying to decipher the long-term effects. Right now, the study is going into year two—we’re trying to see if the effects that we know are in the medium term persist over the long term, and what the duration is likely to be, whether it’s something that will be permanently there, or if it will resolve in time.
Marathe: We have already evaluated and seen more than 350 patients in the one year that we’ve been active and we continue to receive a fair number of referrals every month. We have a waiting list, unfortunately, similar to others in our area. The reality with long COVID is that we don’t have a treatment that universally applies to everybody and that can result in a cure. Because we don’t understand why some people develop long COVID, and why it persists, we continue to provide individualized care plans with the hope of getting the patients through their journey toward a plan to recovery.
Marathe: The most common symptom that we see in the clinic is post-exertional fatigue. Minimal exertion, like talking for an hour, will cause profound exhaustion for the patient, let alone doing their groceries. The second most common is memory fog. We see a lot of patients with autonomic dysfunction, where they have dizziness, palpitations, a combination of symptoms, and a fair number of patients complain of GI symptoms like nausea, vomiting, diarrhea that have either worsened or are new since their diagnosis of COVID-19.
Shepherd: It’s very varied, especially for different patients, and we don’t have a way to really identify who will have it, or for how long. “Long” is an arbitrary term.
Marathe: People who had severe COVID-19 disease are more likely to have long COVID. So, if you were hospitalized or in the ICU because of your original COVID-19 infection, you’re more likely to have long COVID. Similarly, older age and multiple medical problems can lead to longer duration of symptoms after a COVID-19 recovery.

We haven’t noticed it so much in our clinic, but what is reported in literature is that women and people who belong to the transgender community are disproportionately impacted by the symptoms of long COVID. What is underreported is racial and ethnic disparities in the development of long COVID. Over the last 6 months, all of the races and ethnicities have hovered around 10 percent of patients who are reporting symptoms. But I always worry about the disparities, because whether it is underrecognized in specific communities because of lack of knowledge, whether care is accessible to them or not, might be impacting who we are seeing in our clinics.
Marathe: The definition of long COVID is really broad, so it encompasses anybody who has new or worsening symptoms after their diagnosis of COVID-19. We see a lot of mood disorders; a lot of anxiety and depression. For people who had preexisting symptoms and now come to the clinic and say it’s worse after COVID-19, we would still diagnose them with long COVID, but it’s hard to tease out what is progression of that preexisting disease process. If someone has diabetes and they say their control is worse after COVID-19, would it be a natural progression of their disease process, or is it truly related to the COVID-19 disease they experienced? That’s where the challenges come into play.

There is no one-pill-fits-all situation for treatment of long COVID. If you are treating somebody for diabetes or hypertension, it [their treatment] wouldn’t necessarily change. We support them. We say, “Maybe this is long COVID, but we still need to treat you this way.”
Shepherd: We have completed our enrollment—we’ve enrolled 107 participants, most of whom have had COVID; we also have some negative controls. We are trying to retain the patients as we monitor them on a three-month basis to evaluate the progression of their disease and how it evolves with time. The aim is to have a prospective view over four years in total.
Shepherd: …not get COVID.
Marathe: We are going to be a site for a long COVID treatment program called RECOVER Vitals to look at Paxlovid being used for treatment of long COVID. It is in the early stages of roll out, but we expect that it will be rapidly ramped up and provide us with more answers. There are other components to this big study, so the samples can be used with patient participant permission to look at why some people are prone to developing long COVID, and whether there are newer modalities to intervene for prevention or for treatment.
Marathe: Because long COVID was a patient-coined term, it’s quite ambiguous. Some of my patients ask, “Am I going to die with long COVID?” Deaths have certainly been recorded, but not at our location—we haven’t had any deaths from long COVID at BMC. I think the key thing for patients and your readers to take away is: If you are struggling with symptoms, you have to be patient; it’s a matter of time that your body overcomes a lot of the symptoms that you’re experiencing today. Full recovery happens—it’s gradual. A lot of our patients have had full recovery, and we’ve been able to successfully discharge them. For some who have had a slower recovery, having community support around them, and feeling heard as opposed to being invisible—because some of these symptoms are hard to explain—is really important to maintaining a positive outlook on outcomes. Being able to advocate for yourself and engage with the medical community, which a lot of our patients are truly hesitant about doing, is very important as well.

If anybody experiences challenges, then reaching out to long COVID clinics for additional help would be the next step and recognizing that we are here for our patients.
Shepherd: I do mostly inpatient, but we still advocate to patients—even for the patients that we are sending from the inpatient to the outpatient setting—that wearing a mask is protective, both for yourself and those around you, even though it’s no longer a federal or state mandate. It is still practiced within the hospital settings. We still do wear masks during our day-to-day within BMC. We’re still spreading that message that for personal safety it’s recommended.
Marathe: The key to not having long COVID is to never get COVID in the first place, and to do that, masking as well as vaccination—being up-to-date on vaccines—is important. If you do develop COVID-19, you test positive, notify your healthcare provider, because there’s treatments for COVID-19 if you are at risk. It’s preliminary, but there is some data that suggests use of Paxlovid for acute infection may decrease the progression to long COVID. If that holds true, then getting early treatment would also be helpful in preventing the disease.
This interview has been edited for brevity and clarity.
What We Know about Long COVID—and What We Don’t
Andrew Thurston is originally from England, but has grown to appreciate the serial comma and the Red Sox, while keeping his accent (mostly) and love of West Ham United. He joined BU in 2007, and is the editor of the University’s research news site, The Brink; he was formerly director of alumni publications. Before joining BU, he edited consumer and business magazines, including for corporations, nonprofits, and the UK government. His work has won awards from the Council for Advancement and Support of Education, the In-House Agency Forum, Folio:, and the British Association of Communicators in Business. Andrew has a bachelor’s degree in English and related literature from the University of York. Profile
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Given the delay between cause and effect, how do you tease apart effects of other confounders, such as longer-term vaccine side-effects, long term effects from other respiratory diseases, psychosomatic effects, etc.
On the face of it, I can’t see how 107 participants would provide enough statistical power to make such distinctions.
I have suffered from long term Covid since I had Covid in first wave. My symptoms got better after my first vaccination, not worse. There is a huge difference to how I felt before and after. I am doing everything I can to get better, I have the will but nothing works. Any study however small is a huge help and gives me hope.
I suggest you look up Dr Leo Galland’s research, Long Covid: Prevention and Treatment, published January 15, 2023.
Am I contagious when I have fever and chills, which are getting worse with terrible shortness of breathe and fatigue?
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