Study Reveals Insights into Long COVID Trajectories in Adults

New research led by Mass General Brigham followed more than 3,500 patients, finding that 10.3% had symptoms consistent with long COVID three months after infection, 81% of whom continued to experience persistent or intermittent symptoms a year later.

Millions of patients have developed long COVID, a chronic condition that involves a range of symptoms, including fatigue, brain fog, dizziness, and palpitations that persist for at least three months after SARS-CoV-2 infection. In a new analysis of adult participants in the NIH funded Researching COVID to Enhance Recovery (RECOVER) Initiative, Mass General Brigham researchers identified eight different trajectories that long COVID can take, depending on severity, duration, and whether symptoms improve or worsen. Their findings are published in Nature Communications.

“This study addresses an urgent need to define the differing long COVID trajectories,” said senior author Bruce Levy, MD, of the Mass General Brigham Department of Medicine and the Division of Pulmonary and Critical Care Medicine. “Our findings will help determine what resources are needed for clinical and public health support of individuals with long COVID and will also inform efforts to understand long COVID’s biological basis.”

To identify long COVID trajectories, the researchers followed 3,659 adult RECOVER participants who first contracted SARS-CoV-2 during the Omicron variant era (after Dec. 1, 2021). The participants completed a comprehensive symptom questionnaire at 3-, 6-, 9-, 12-, and 15-months post-infection to track changes over time. Then, the researchers identified patients with long COVID using the long COVID research index, a symptom-based tool that was previously developed by Mass General Brigham researchers.

Overall, 10.3% of patients had long COVID symptoms three months after infection, and 81% of these patients continued to experience persistent or intermittent symptoms a year later. Female patients and those who had been hospitalized with an acute SARS-CoV-2 infection were more likely to develop persistently severe long COVID symptoms.

The researchers identified eight different long COVID trajectories. Some of these trajectories included persistently severe symptoms, intermittently severe symptoms, gradually improving symptoms, gradually worsening symptoms,and mild symptoms that only appeared after 15 months. 

“The variability we identified will enable future studies to evaluate risk factors and biomarkers that could explain why patients vary in time of recovery, and help identify potential therapeutic targets,” said first author Tanayott Thaweethai, PhD, assistant professor at Massachusetts General Hospital Biostatistics.

Authorship: In addition to Levy and Thaweethai, Mass General Brigham authors include Andrea S. Foulkes (co-senior author), and Daniel J. Shinnick. Additional authors include Sarah E. Donohue, Jeffrey N. Martin, Mady Hornig, Jarrod M. Mosier, Hassan Ashktorab, Ornina Atieh, Andra Blomkalns, Hassan Brim, Yu Chen, Melissa M. Cortez, Nathan B. Erdmann, Valerie Flaherman, Paul Goepfert, Jason D. Goldman, Naomi M. Hamburg, Jenny E. Han, James R. Heath, Vanessa Jacoby, Sarah E. Jolley, J. Daniel Kelly, Sara W. Kelly, C. Kim, Jerry A. Krishnan, Rebecca Letts, Emily B. Levitan, Matthew E. Modes, Grace A. McComsey, Torri D. Metz, Janet M. Mullington, Igho Ofotokun, Megumi J. Okumura, Claudia Castillo Paredes, Thomas F. Patterson, Michael Peluso, Rebecca Reece, Zaki A. Sherif, Hyagriv N. Simhan, Christopher Simmons, Upinder Singh, Barbara S. Taylor, Brittany D. Taylor, Joel D. Trinity, Andrea B. Troxel, Paul J. Utz, Andrew J. Vasey, Elisheva Weinberger, Zanthia Wiley, Juan Wisnivesky, and Lynn M. Yee, and Leora Horwitz on behalf of the RECOVER Adult Cohort.

Disclosures: A full list of disclosures can be found in the paper.

Funding: This research was funded by the National Institutes of Health (OTA OT2HL161841, OT2HL161847,  OT2HL156812, and OT2HL162087) as part of RECOVER. Additional support for T.T., A.S.F., and B.D.L. was provided by grant R01 HL162373.

Paper cited: Thaweethai, T et al. “Long COVID trajectories in prospectively followed RECOVER Adult participants” Nature Communications DOI: 10.1038/s41467-025-65239-4