Dozens of people at the Brigham have worked behind the scenes to join a national effort to understand long COVID, including (from left): Phyo Phyo Min (Vivian) Thu, Kwabena Lartey, Maureen Whittelsey, Li Chen, Bruce Levy and Rebecca Wiener. Photo by Dylon Crowley-Perez

Before she began meeting participants for a study of long COVID, Li Qing Chen, a program director in the Brigham’s Pulmonary Division, had little direct experience with the long-term effects of COVID-19. But the conversations Chen has had with participants have stayed with her.

“Hearing their stories and the effects that their symptoms have had on their daily lives — even among those who were infected early in the pandemic — and how they are still deeply affected has helped me focus on why this work is so important to move forward,” said Chen.

Chen is one of dozens of people at the Brigham who have helped launch the greater Boston COVID Recovery Cohort (BCRC), a consortium of six sites in the Boston area that are taking part in a nationwide study of the long-term effects and prolonged symptoms of COVID-19. Together, the sites will recruit 909 participants over the next year as part of the National Institutes of Health (NIH) “Researching COVID to Enhance Recovery” (RECOVER) Initiative. The initiative’s goal is to better understand and define the constellation of long-term complications that can occur after infection and lay the groundwork for preventing and treating symptoms.

The BCRC, for which the Brigham is the primary site, officially launched at the beginning of March 2022, but work has been going on behind the scenes for the last year to set the BCRC up for success.

“We have many local heroes who have worked tirelessly to help launch this study and foster collaboration across not only departments but also across health systems,” said contact principal investigator Bruce Levy, MD, chief of the Pulmonary Division and site lead at the Brigham. “We would not be where we are today if not for their efforts to work together to help reach the shared goal of better understanding long COVID so that we can, ultimately, improve the lives of patients.”

When Infection is Just the Beginning

More than two years into the pandemic, critical questions about long COVID loom large. Symptoms can vary widely but often include pain, headaches, fatigue, “brain fog,” shortness of breath, anxiety, depression, fever, chronic cough and sleep problems. For some people, symptoms of infection last weeks or months; for others, new symptoms may appear after the infection has passed. Through the RECOVER initiative, investigators will look for commonalities among people experiencing symptoms to begin to understand the potential causes and prevalence of long COVID.

Buoyed by Teamwork

Efforts to recruit participants are now underway at the Brigham as well as its five partner sites at Mass General, where co-principal investigator Ingrid Bassett, MD, MPH, serves as site principal investigator, Beth Israel Deaconess Medical Center, Boston Medical Center, Cambridge Health Alliance and Tufts Medical Center. As part of the RECOVER adult cohort, Boston researchers are recruiting patients with long COVID as well as patients who have recently been diagnosed with COVID-19. They plan to follow participants in both groups to understand who develops symptoms, how long symptoms persist and answer other basic questions about long COVID.

Bringing the six sites together to form the BCRC took a degree of coordination and collaboration across health systems rarely been seen before.

Christopher Corsini, a grant administrator in the Pulmonary Division who has been at the Brigham for eight years, recalled first hearing about the NIH’s call for proposals related to long COVID last February.

“I remember Dr. Levy coming into my office and saying, ‘Get ready!’” said Corsini. “We knew this was going to be a big grant application, but what was really unique here was the opportunity to work across departments and hospitals, with the Brigham serving as a hub for a multi-center collaboration.”

Timothy Gomperts, Jr., works in the Central Research Management Office for Mass General Brigham and, like Corsini, was heavily involved in the pre-award application process.

“What made this special was that this was like moving at warp speed,” said Gomperts. “Usually, it takes a lot of time before the federal government would even allocate the funds and make the announcement, and usually the call for proposals would be a lot more prescribed and have a narrower process. That wasn’t the case here.”

Laurel Cobban, director of Research Administration within the Department of Medicine, recalls attending a Zoom call in early March 2021 and hearing about the exhaustive list of outstanding work that needed to be completed in just three weeks. She immediately offered to help.

“I had a sense that this could be one of the most important questions that I might be able to help answer,” said Cobban. “I was very impressed with the team that was already present, including colleagues at MGH and MGB whom I’d worked with previously and knew well. At every turn, team members poured themselves into the work. We buoyed one another through the long hours.”

A Bold Path to Collaboration

The effort’s unusual path required both flexibility and teamwork. The process also benefited from brainstorming across the Brigham research community. On Feb. 24, 2021, the day after the NIH made the first in a series of Research Opportunity Announcements (ROAs),  more than 100 Brigham investigators came together over Zoom to take part in a “Think Tank” meeting about the clinical challenges that patients with long COVID face and some of the research questions that needed to be addressed. Mass General held a similar forum that was also well attended.

“It was very exciting to see that people from all corners of the hospital community are extremely energized and motivated to work on this,” said Allison Moriarty, MPH, senior vice president of Research Planning & Operations and Innovation.

Moriarty, Levy and colleagues teamed up with Bassett and her colleagues at Mass General. Together, they identified key faculty members from across Mass General Brigham and organized working groups focused on symptoms related to organ systems affected by long COVID, including pulmonary, neurological, cardiovascular, immunological, endocrine, sleep and renal effects. The team also established a working group focused on health disparities, community engagement and recruiting diverse participants.

Soon, it became clear that the collaboration could extend beyond Mass General Brigham, and experts from beyond the system were invited to the discussion.

“This was a quintessentially interdisciplinary team,” said Cobban. “This was very much a joint venture between physician scientists, biostatisticians, project managers, grant administrators and hospital leadership. I would be remiss if I didn’t mention Allison Moriarty’s leadership, in particular. She made the impossible possible.”

Answers from Autopsies

As part of the national initiative, James R. Stone, MD, PhD, of the Department of Pathology at Mass General, and Robert Padera, MD, PhD, of the Department of Pathology at the Brigham, will lead local efforts to conduct a human tissue study. Using clinical samples collected at autopsy, they hope to better understand the virus’ effects on different organ systems and search for evidence of viral persistence. Stone notes that in autopsies of people who have died of COVID-19, his team has detected the virus in heart tissue weeks after infection. A study by researchers at the NIH, currently posted as a preprint, reports detecting the virus throughout the body and brain months after infection. Other viruses, such as varicella and Epstein Barr, stay in the body long after infection and can cause symptoms to flair years later in a small percentage of people. It is unclear if SARS-CoV-2 can latently persist like these viruses and, if so, if this causes symptoms.

“One of the major questions we want to address is: Is long COVID due to viral persistence or to something else?” said Stone. He notes that viral persistence is one of several hypotheses — another is that infection triggers a new form of autoimmune disease. Yet another theory is that people with long COVID are experiencing symptoms of a chronic coagulopathy, a form of blood clotting triggered by infection.

“Autopsy may help sort out the answers, but we only have a critical window of time — just 24 hours after a person with long COVID dies — to find clues to help answer these critical questions,” said Stone. Mass General and the Brigham will serve as one of five sites across the country that, cumulatively, intend to perform 700 autopsies in the next four years as part of the study.

Pride in Accomplishment

After months of intense work, planning and submission, seeing the BCRC launch has had special meaning to those working behind the scenes.

“I am so grateful to everyone who has worked to make this a reality,” said Moriarty. “It shows that there’s power in breaking down artificial barriers and collaborating toward a common goal.”

Chen, who has now trained others to recruit participants for the study, is also impressed by the commitment of patients.

“There are many study participants who just want to help and want to bring awareness to long COVID,” she said. “One person I talked to told me that even if the study would not help them personally, they wanted to be a part of it because it might help people in the future. That’s how we feel too — we need more data so that we can help people who continue to experience these long-term effects.”