Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort.

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.