IMPORTANCE: Long COVID is characterized by persistent symptoms after SARS-CoV-2 infection, with inflammation playing a key role in pathogenesis. Colchicine, an established anti-inflammatory agent, may reduce these symptoms by targeting inflammatory pathways.
OBJECTIVE: To evaluate the superiority of colchicine over placebo in improving functional outcome at 52 weeks from baseline.
DESIGN, SETTING, AND PARTICIPANTS: This double-blind, 1:1 randomized clinical trial recruited participants with confirmed SARS-CoV-2 infection and persistent symptoms from 8 hospitals in 6 states in India between January 2022 and July 2023. Individuals were eligible if they had functional limitation (Post-COVID-19 Functional Status scale grade 2 or more) and/or elevated inflammatory markers (high-sensitivity C-reactive protein >0.20 mg/dL and/or neutrophil to lymphocyte ratio >5). Outcomes were assessed at 12, 26, and 52 weeks after randomization. Data were analyzed from January to February 2025.
INTERVENTIONS: Participants were randomly assigned to receive colchicine, 0.5 mg, once or twice daily, based on body weight, or placebo for 26 weeks.
MAIN OUTCOMES AND MEASURES: The primary outcome was the change in distance walked during a 6-minute walk test from baseline to 52 weeks. Secondary outcomes included changes in inflammatory markers and patient-reported outcome measures, such as quality of life, anxiety, depression, fatigue, dyspnea, measured using validated instruments.
RESULTS: Of 346 participants included in the modified intention-to-treat analysis, 209 (60.4%) were female, 137 (39.6%) were male, and the mean (SD) age was 46 (12) years. At 52 weeks, there was no difference in mean (SD) change in 6-minute walk test distance between the colchicine and placebo groups (colchicine, 35.5 [19.76] m; placebo, 29.96 [19.83] m; mean difference, 5.59 m; 95% CI, -9.00 to 20.18; P = .45). Similar null findings were seen across all predefined outcomes, except for a small, nonclinically relevant difference in the mean (SD) ratio of forced expiratory volume in 1 second to forced vital capacity (colchicine, -0.02 [0.03]; placebo, -0.06 [0.03]; mean difference, 0.04; 95% CI, 0.02 to 0.07; P = .001).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among adults with long COVID, colchicine did not improve functional capacity, respiratory function, or inflammatory markers. These findings underscore the need to explore alternative therapeutic approaches for long COVID.
TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2021/11/038234.
