Does having multiple COVID infections lead to more lung scarring and breathing problems? What impact does the virus have on the brain?
For many who contracted COVID, the symptoms don’t end with the infection. Fatigue, brain fog, and chronic cough persist for months or years. With few treatment options, long COVID remains a medical mystery.
Now, pathologists at the Duke University School of Medicine are taking a closer look. With a two-year, $1.3 million grant from the National Institutes of Health, they will be the first to study long COVID’s effect at the tissue level. As principal investigator in the NIH-funded RECOVER initiative, Carolyn Glass, MD, PhD, a Duke heart and lung pathologist, joins more than 30 research teams nationwide working to understand long COVID and its causes and ways to treat it. Her team will analyze thousands of biopsy slides to see how the virus affects the brain, nerves, muscles, and lungs.
“This study will hopefully provide long-awaited answers,” said Glass, associate professor of pathology and director of the Duke University Hospital Autopsy Service.
Tissue Pathology Study
Duke will be a site for the Tissue Pathology Study, a project focused on the biological mechanisms of long COVID. Researchers will examine whether repeat infections shorten life expectancy and if social and environmental factors impact recovery from COVID.
“One reason Duke was chosen is because of our commitment to addressing health care disparities,” Glass said. “It’s critical that clinical research reflects our diverse patient population.”
The study has two phases: first collecting autopsy tissue and body fluid samples; second, examining about 8,000 biopsy slides. With family consent, they will also gather additional specimens and clinical data from autopsies of those with a history of COVID.
“Autopsy studies give us the unique opportunity to see the long-term effect of infection at the tissue level,” said Glass, who is chief of Duke Cardiovascular Pathology Service and also an assistant professor of cardiothoracic surgery.
“For example, a lung tissue stain can reveal scarring. If a patient knew this in advance, it could guide medical decisions,” Glass said.
Samples will be stored in the national COVID Biorepository Core at Mayo Clinic, alongside samples collected at New York University Langone Health (NYU); Johns Hopkins Medicine; Massachusetts General Hospital; University of Alabama at Birmingham; and the University of New Mexico who are also participating in the Tissue Pathology Study.
For the second phase of the study, Duke pathologists will be the first to define long COVID’s tissue-level effects on different parts of the body.
Co-investigators Huihua Li, MD, a thoracic pathologist and assistant professor of pathology, will work with Glass to review lung tissue, while Shih-Hsiu “Jerry” Wang, MD, PhD, associate professor of pathology and neurology, will focus on the brain and nervous system. Karra Jones, MD, PhD, associate professor of pathology, and Wang will also examine nerve and muscle tissue.
“It would be helpful to know if someone with multiple COVID infections has increased scarring in their lungs which could impact breathing ability,” said Glass. “This would be important information for physicians to know as they treat patients or plan procedures.”
Team Collaboration
Duke research coordinators Ameera Afifi and Haley Brown will manage consent and logistics, ensuring proper sample collection and data entry. Duke pathologists’ assistants will collect specimens during autopsies, which will be sent to the Mayo BioRepository Core.
Glass’s team aims to analyze all slides by April 2026 and share findings with the NIH that spring. The Mayo Biorepository Core will later be open to other researchers for future studies.
For questions or to learn more about the study, contact Beth Handel, senior regulatory coordinator for pathology.