Researchers Race to Understand Long COVID in National Study
For medical providers working with COVID long-haulers, “no two patients are the same,” pointing to the urgency of unraveling the mysteries of post-coronavirus conditions, potential treatments
Among the uncertainties and worries that living with COVID-19 presents, long COVID—lingering effects of the disease that persist longer than four weeks after an initial infection clears—is a big one. Patients with long COVID, sometimes dubbed “COVID long-haulers,” report symptoms ranging from headaches to chronic fatigue to shortness of breath; the long-term impacts of the condition are largely unknown.
To answer the many puzzling questions about long COVID, researchers at Boston University’s School of Medicine and Boston Medical Center (BMC) are beginning to investigate “post-acute sequelae of SARS-CoV-2 (PASC),” the medical term used for the array of long COVID symptoms. The newly launched project, called the RECOVER (Research COVID to Enhance Recovery) study, is part of a national effort—funded by the National Institutes of Health—that aims to better understand who is at risk, how recovery varies in different people, and what can be done to prevent the condition and treat patients.
Being able to fully understand long COVID starts with being able to properly define it, says Jai Marathe, a coprincipal investigator on the RECOVER study. She says that’s been difficult since symptoms are so varied.
“Patients with long COVID may present with a variety of different symptoms, and no two patients are the same,” says Marathe, a BU School of Medicine assistant professor who specializes in infectious diseases. “The important thing to note is that we are learning about long COVID along with our patients—and we are constantly evaluating our treatment recommendations to address the patients’ needs. For some, [symptoms] are mild, but can be debilitating for others.”
Marathe is also the founding director of the ReCOVer Long COVID Clinic at BMC, a multidisciplinary clinic with specialties that include neurology and behavioral health and currently has about 85 patients under its care. The RECOVER study will recruit from the clinic and also have a control group of people who are not displaying signs of long COVID.
“The tough part to date has been that studies have used different definitions of long COVID. A well-controlled cohort like this one, with a large number of patients, can help clarify the biological and clinical features that are hallmarks of PASC,” says Nahid Bhadelia, an infectious diseases expert and BMC physician, a BU School of Medicine associate professor, and founding director of BU’s Center for Emerging Infectious Diseases Policy & Research. Bhadelia is a coprincipal investigator on the RECOVER study—which will take place over the next three years—and is helping BMC collaborate with five other Boston–area hospitals that are also a part of the national project.
To learn more about the study and the effects of long COVID, The Brink spoke with Anna Cervantes-Arslanian, a coinvestigator on the project and a neurologist at BMC—the primary teaching hospital of the BU School of Medicine—who works with patients in the long COVID clinic. She’s also a neuro-ICU specialist and BU School of Medicine associate professor of neurology, neurosurgery, and medicine. Cervantes-Arslanian recently led a study for the Society for Critical Care Medicine involving over 16,000 patients hospitalized with COVID-19 to look at associated risk factors and serious neurologic outcomes, like encephalopathy, stroke, and seizure.
with Anna Cervantes-Arslanian
The Brink: What has your experience been like caring for patients with long COVID?
Cervantes-Arslanian: In my experience, long COVID symptoms are highly varied. Because of my day-to-day practice in the ICU, most of the patients referred to me are following up after they have been hospitalized with severe illness from COVID-19. Many of these patients had symptoms that could be related to being hospitalized or related to SARS-CoV-2. Now, we’re seeing more people coming to the [long COVID] clinic who were not hospitalized to begin with, some who didn’t even have a respiratory infection.
I am often consulted for severe changes in mental status; sometimes strokes, seizures, and very rarely, other obscure problems after a COVID-19 infection. Now, the number one symptom I’m hearing about is fatigue. People talk about persistent fatigue that is totally different from what their baselines were [before they were infected with COVID-19]. People also talk a lot about brain fog, which is experienced differently for many people, but often described as feeling scatterbrained, or at a loss for words. There are also a lot of patients who have headaches, either a new onset or worsening headaches, or headaches that started with a COVID infection. There are also a lot of symptoms that dovetail into cardiology, such as where people have abnormal and rapid heartbeats depending on if they are laying down or standing up. All of these neurologic symptoms can be debilitating for some people.
The Brink: What are you and the research team hoping to accomplish by the end of this study?
Cervantes-Arslanian: There is a loose definition of post-acute sequelae of SARS-CoV-2, or PASC, so I think clearly defining this syndrome is very important—future research will depend on us being able to communicate what PASC is. Another key question I’d like to answer is, are these symptoms more common in people with SARS-CoV-2 or not? That sounds like a strange question, but we need to have an answer for this. We need a control group, which the RECOVER study will have.
Having the long COVID clinic is also important for specialists to evaluate whether concerns a patient attributes to long COVID are indeed related to the infection reaction or potentially signs of another illness that needs attention. As an example, I had a patient who went to her primary care doctor with a headache after getting COVID-19, and then her doctor referred her to me. Once I saw her, I immediately saw she had a serious problem, possibly a brain tumor, that likely by coincidence appeared after getting COVID.
The Brink: In your opinion, why is studying long COVID urgently needed right now?
Cervantes-Arslanian: This is a brand-new, novel virus that has impacted the whole world. It’s important for us to understand the acute complications—how the virus impacts the body during an infection—and what the long-term effects are going to be. We know that after the flu pandemic in 1918, there was an increased risk for a type of post-viral Parkinson’s disease, so [the long-term effects] are something the medical community is thinking about. What we really don’t know is: Will infected kids have long-term medical problems? Will this impact middle-aged adults when they get older? We just don’t know. I’m very interested from a place of curiosity, as well as getting the information as the starting point.
What is most important right now is that we are really paying attention to these patients, because people feel dismissed. Women are more likely to have these symptoms than men, and women are more often dismissed [in medical settings] for vague symptoms.
The Brink: What do we know about whether the vaccine has any impact on the likelihood of developing long COVID?
Cervantes-Arslanian: So far, it seems that being vaccinated makes you less likely to develop long COVID symptoms, but we don’t know for sure. There are a lot of reasons to get vaccinated, so possibly being less likely to develop long COVID is another reason. Long COVID could also be more associated with particular virus variants, but again, we don’t know. There were also stories of some people experiencing improvements in long COVID symptoms after getting the vaccine, which some people point out could be a placebo effect. But there are reasons to think that the immune system is involved with long COVID, so it’s logical to think that providing the spike protein for the boosted immunity can help in the other processes involved.
This conversation was edited for length and clarity.