Resistance Exercise Therapy After COVID-19 Infection: A Randomized Clinical Trial

JAMA Netw Open. 2025 Nov 3;8(11):e2534304. doi: 10.1001/jamanetworkopen.2025.34304.

ABSTRACT

IMPORTANCE: Long COVID presents an unmet therapeutic need.

OBJECTIVE: To determine the effects of a resistance exercise intervention on exercise capacity, health status, and safety among adults after COVID-19 infection.

DESIGN, SETTING, AND PARTICIPANTS: A 2-arm, multicenter, randomized clinical trial including 233 adults with a hospital or community diagnosis of COVID-19 infection in the preceding 12 months was undertaken from June 1, 2021, to April 26, 2024. The intervention group comprised 117 individuals, and the control group comprised 116 individuals. A total of 224 individuals at baseline and 193 individuals at 3 months completed Incremental Shuttle Walk Tests.

EXPOSURES: The intervention group received the personalized resistance exercise intervention for 3 months, and the control group received treatment as usual.

MAIN OUTCOMES AND MEASURES: The primary outcome was the distance achieved (in meters) in the Incremental Shuttle Walk Test undertaken 3 months after randomization. Secondary outcome measures included health-related quality of life (measured by the European Quality of Life 5-Dimension 5-Level Instrument [EQ-5D-5L]), anxiety and depression (measured by the Patient Health Questionnaire), and grip strength.

RESULTS: A total of 233 adults (median age, 53.6 years [IQR, 43.8-60.8 years]; 146 women [62.7%]; 91 [39.1%] hospitalized with COVID-19 infection) were randomized (117 [50.2%] to the intervention group and 116 [49.8%] to the control group). The median percentage adherence with the exercise intervention was 71.0% (IQR, 47.8%-96.8%), equivalent to performing the exercises 5 days per week. The mean (SD) distance achieved in the Incremental Shuttle Walk Test was 328 (225) m for 224 individuals at baseline and 389 (249) m for 193 individuals at follow-up. The mean (SD) change in Incremental Shuttle Walk Test distance at 3 months compared with baseline was 83 (118) m in the intervention group (n = 94) and 47 (95) m in the control group (n = 98) (adjusted mean difference, 36.5 m [95% CI, 6.6-66.3 m]; P = .02). By 3 months, compared with the control group, greater improvements in the intervention group were also observed for the health-related quality of life utility score (EQ-5D-5L) (0.06 [95% CI, 0.01-0.11]; P = .02), Patient Health Questionnaire category (0.5 [95% CI, 0.2-0.8]; P = .01), and handgrip strength (2.6 kg [95% CI, 0.9-4.2 kg]; P = .002).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a 3-month program of resistance exercise among adults after COVID-19 infection appeared to improve walking distance, health-related quality of life, anxiety, depression, and grip strength. This pragmatic intervention may be a generalizable therapy for individuals with persisting physical symptoms after COVID-19 infection.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04900961.

PMID:41213124 | DOI:10.1001/jamanetworkopen.2025.34304