OBJECTIVE: To evaluate the likelihood of improvement among persons with likely LC.

DESIGN: Prospective, multisite cohort study (RECOVER-Adult [Researching COVID to Enhance Recovery]).

SETTING: 83 U.S.-based sites across 33 states; Washington, DC; and Puerto Rico.

PARTICIPANTS: 1019 persons in RECOVER-Adult with likely LC (LC Research Index [LCRI] ≥11) 12 months after first SARS-CoV-2 infection.

MEASUREMENTS: The primary outcome was time until 2 consecutive study visits with LCRI less than 11. Secondary outcomes were time until LCRI measure reduced 50% or more and quality of life was good or better, and LCRI decreased to 0. Unadjusted estimates of cumulative incidence and adjusted marginal cumulative incidence by age, sex, SARS-CoV-2 wave, and LC subtype were reported across all follow-up time points.

RESULTS: An estimated 36.2% (95% CI, 33.0% to 39.5%) met the primary outcome by 24 months after infection, and 50.1% (CI, 46.1% to 54.0%) met the primary outcome by 36 months. An estimated 56.4% (CI, 52.2% to 60.4%) and 26.9% (CI, 23.3% to 30.5%), respectively, met the 2 secondary outcomes by 36 months. Among persons who still reported likely LC at 18 months and 24 months after first infection, relative timing of subsequent symptom improvement was similar.

LIMITATION: Findings in this observational cohort are interpretable in a population with prevalent likely LC and do not address causal relationships between individual characteristics and symptom improvement.

CONCLUSION: Among persons with likely LC 12 months after initial SARS-CoV-2 infection, one half experience meaningful reductions in symptoms by 36 months, whereas a quarter experience complete remission of symptoms. These findings underscore both the potential for natural recovery and the urgent need for placebo-controlled therapeutic intervention trials.