Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort
Thaweethai, T; Donohue, SE; Martin, JN; et al., Nature Communications, November 2025
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Short Summary
In this RECOVER study, researchers wanted to find out how Long COVID symptoms change over 15 months. To do this, researchers studied 3,659 adults who had COVID-19 before joining the RECOVER study or while they were enrolled. Researchers found that Long COVID does not look the same in everyone. Instead, people’s Long COVID symptoms usually fell into 1 of 8 different patterns over time. While most people felt better after recovering from COVID-19, about 1 in 20 participants had symptoms of Long COVID that lasted throughout the entire study. About 3 in 25 participants with Long COVID had symptoms that came and went. Other participants did not have Long COVID symptoms early on but started having health problems many months after having COVID-19. These findings show that doctors should continue monitoring patients for a long time after they have COVID-19 because their symptoms can stay, come and go, or start several months after getting sick. Understanding these patterns will help researchers find better ways to prevent and treat Long COVID in different groups of people.
This summary was prepared by the RECOVER Initiative.
Publication Details
DOI: 10.1038/s41467-025-65239-4
Abstract
Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments.
Authors
Tanayott Thaweethai, Sarah E Donohue, Jeffrey N Martin, Mady Hornig, Jarrod M Mosier, Daniel J Shinnick, 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 J 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, Lynn M Yee, Leora Horwitz, Andrea S Foulkes, Bruce D Levy, RECOVER-Adult Consortium
Keywords
Humans; COVID-19/epidemiology/physiopathology/virology; Female; Male; United States/epidemiology; Adult; Middle Aged; Prospective Studies; SARS-CoV-2; Longitudinal Studies; Aged; Post-Acute COVID-19 Syndrome