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There are almost as many questions about long Covid as there are symptoms. From the pandemic’s early days, a significant share of people have been troubled by problems that persist for weeks or even years after their acute infection clears, or find they’ve developed new issues that range from bothersome to debilitating. These difficulties span the mind and the body, and so far they resist explanation.

Current treatments focus on easing brain fog, bone-wearying fatigue, shortness of breath, muscle pain, loss of smell, anxiety and depression, and sleep problems, but two burning questions remain unanswered: Who gets long Covid and how can it be prevented?


On Monday, a consortium of six Boston hospitals (Beth Israel Deaconess Medical Center, Boston Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Massachusetts General Hospital, and Tufts Medical Center) joined RECOVER, a national, 15-member effort sponsored by the National Institutes of Health whose mission is to understand, prevent, and treat long Covid, which it calls post acute sequelae of SARS-CoV-2 infection, or PASC.

Mass. General infectious disease physician Ingrid Bassett, also a co-principal investigator of RECOVER and site principal investigator of the study, spoke to STAT about how her hospital and others in Boston are approaching the study of adults, which seeks representation from all people affected by Covid. That means not just those who come to long Covid clinics, patients who may not reflect racial and ethnic groups hit disproportionately hard during the pandemic. In Boston, as in 15 other study sites around the country, volunteers will be recruited at community health centers as well as the academic medical centers where the researchers may be based, adding up to 200 or more sites, including rural areas and Native American reservations.

Volunteers who have had Covid — the Boston study seeks to enroll around 900 adults — will participate in tiers, from answering questionnaires to having physical exams to undergoing imaging tests, and they will be followed for three years. People who have recovered without long-term symptoms will serve as controls, and tissue samples from autopsies will provide additional information.


“We’re really trying to understand that trajectory of recovery and what some of the factors are generally associated with someone recovering or not from this illness,” Bassett said.

This conversation has been lightly edited for length and clarity.

How do you define long Covid?

One of the very interesting challenges is that long Covid is both our study outcome and something that we are still trying to define. As a scientist, usually your study outcome needs to be very well-defined before you begin. But in our case, we don’t have that luxury because this is an emerging condition.

So what did you settle on?

Based on consensus, essentially, the NIH is defining it as either persistent symptoms after 30 days from the time of acute infection or the development of new symptoms. We have a whole series of questions that we’re asking participants in the study related to really every symptom or every system you can think of from complications that have been observed already: problems with cognition or attention or people feeling tired after they exert themselves even only a little bit, or shortness of breath, blood clots.

It may also be that by doing the study with such a large group of participants that we also see fine signals for things that arise after acute infection that we don’t yet know.

Besides scale, what’s different about this study?

It’s the strategy of enrolling people at the time of their acute infection and really understanding the circumstances of their acute infection: how sick they were, what treatments did they get, were they vaccinated. I think if you want to know how likely it is that people will develop long Covid, it’s all of these factors, and then following them over time. Some of them will recover fully and some of them won’t, and we’re really trying to understand that trajectory of recovery and what some of the factors are generally associated with someone recovering or not from this illness. So I think the acutely infected participants are really powerful.

It also helps us understand if 100 people who have SARS-CoV-2 infection and who were infected around the same time and you are seeing a similar strain, how likely is it that they’re going to go on to develop these symptoms?

What else will your study do?

I hope this will raise awareness about long Covid and that people will be able to seek care. At the moment, there are no proven treatments for treating long Covid, so a lot of times it’s a rehabilitation approach that’s taken. Our study won’t be offering that specifically, because we’re really observing what’s happening, but if people have symptoms, they can be referred into the long Covid clinics. I think over time, as we get a better understanding of the underlying biology, these will likely be more targeted treatments.

What do we need to know?

The main questions are: What is the incidence and prevalence of people developing these long Covid symptoms? What does this look like? Anecdotally, we see some people have more of a predominance of cognitive issues or shortness of breath or pulmonary issues. And so really trying to understand those phenotypes and then thinking about what are the risk factors that predict the development of long Covid and then finally trying to understand what is the mechanism that underlies the development of this condition. Because we need to understand that to be able to think about therapies.And potentially things we can do at the time of the acute infection that might prevent the development of long Covid.

How do you make sure your study is inclusive of people hardest hit by Covid-19?

Certain minority populations were overrepresented in the cases of acute SARS-CoV-2 and in some cases in the hospitalizations for SARS-CoV-2. So to try to capture that, the NIH enrollment goals are, for example, 27% of participants being Hispanic or Latinx, and 16% being African American. So these proportions are larger than these groups represent in the U.S. population in general and that’s really intentional, understanding those communities were very hard hit.

In Boston, one of the ways we’re doing that is through not only enrolling participants at the main academic center, which may be less accessible for certain people, but also going to our community health center partners. At Mass. General, we have started to enroll participants, both acutely infected and post-acute patients, at the Chelsea community health center. We saw Chelsea as a very hard-hit area where there’s a lot of engagement already with the community there around Covid. So this was a natural extension to say, “This is something that’s affected your community. And we’re hoping that you can be part of the next steps for trying to treat and prevent this condition.”

Your background is in HIV research, like many others engaged in Covid — including your colleague Rochelle Walensky, now CDC director.

We are many! When I get onto principal investigator calls that are nationwide, there are lots of familiar faces from the HIV research community.

How does your experience in HIV relate to Covid?

For me there are a lot of parallels. I started working in South Africa in 2004 when the President’s Emergency Plan for AIDS Relief was just starting to provide money. I think one of the most exciting things about this for me, as a researcher whose whole career has been doing research in South Africa, is this focus on equity by the NIH.

In PEPFAR, some of what they did well was not just thinking about having the medications available or on the tarmac at the airports, but actually thinking about the health systems required to deliver those medications effectively. So in terms of engaging community health workers and traditional healers, in terms of developing monitoring and evaluation strategies, in terms of developing training for health care workers, in terms of developing messaging for the public around treatment for HIV. And so they really took a very holistic approach.

I think in some ways that’s what’s needed to achieve equity for vaccination and for treatments for acute SARS-CoV-2. Because now that oral antiviral therapies are becoming available, there’s going to again be questions around equity and access for those treatments as there have been questions about equity and access for vaccines.

I think an infectious disease essentially dictates that we’re all in this together, and that means we need to figure out how to engage communities and get vaccinations and treatments to communities in a way that thinks about this as a global problem.

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