Exercise Program Manages Persistent Symptoms Post-COVID-19 Infection

A program of resistance exercise for 3 months in adults following COVID-19 infection demonstrated improvements in health-related quality of life, anxiety, depression, walking distance, and grip strength, according to results from a randomized clinical trial (NCT04900961) published in the Journal of the American Medical Association.^1,2

The results provide evidence for the benefits of pragmatic interventions such as these for patients struggling with persistent physical symptoms following COVID-19 infection. Also characterized as post-acute sequelae of SARS-CoV-2, or long COVID, the condition can lead to sustained COVID-19 symptoms, such as fatigue and breathlessness, after infection, lasting 3 months or longer.^1,3

How Can Exercise Improve Long COVID Symptoms?

Beyond lasting physical impairments, long COVID can impact a patient’s psychological profile and exercise capacity. Research demonstrates reductions in skeletal muscle mass and function are possible in individuals living with long COVID, leading to and reinforcing physical inactivity. Resistance exercise may play a role in this setting.^4,5

Integrating exercise interventions for people with long COVID has been shown to improve exercise capacity, dyspnea, and health-related quality of life. Despite positive indications, research focused on these associations has been saddled by low certainty of evidence, an overestimation of treatment effects, and limited data on adverse events. Thus, a randomized clinical trial assessing the cause-and-effect relationships between resistance exercise and long COVID outcomes was sorely needed.^5,6

Consequently, using previous experiences from previous research initiatives centered on exercise and long COVID, the current authors sought to determine the impact of a resistance exercise intervention on health status, exercise capacity, and safety in adults following a COVID-19 infection. The investigators initiated a multicenter, parallel-group, randomized trial in Scotland from June 2021 to April 2024, enrolling and randomly assigning 233 individuals (median age, 53.6 years; 146 women and 87 men).¹

How Was the Clinical Trial Organized?

The exercise program occurred in community and hospital settings. Individuals were asked to perform the exercises daily while logging their exercise repetitions and progress. Interventions were tailored to the preferences of each participant and their corresponding progress. Every other week, participants were contacted by the research team through video or telephone to provide support and guidance.

The authors primarily sought to demonstrate improvements in distance achieved during the Incremental Shuttle Walk Test, which measures exercise capacity. Secondary outcomes included respiratory function (assessed using spirometry), physical function (measured using handgrip strength), and patient-reported outcome measures.¹

In total, 117 individuals (50.2%) were assigned to the intervention group, and 116 individuals (49.8%) were assigned to the control group. Over 60% of the population reported experiencing symptoms 90 days or more following the diagnosis of COVID-19.¹

Did Exercise Positively Impact Exercise Capacity and Quality of Life?

Positive observations were made regarding adherence. The median percentage of participants adhering to the exercise intervention was 71.0% (IQR, 47.8%–96.8%), which was equivalent to performing the exercises 5 days per week.¹

Mean distance achieved in the Incremental Shuttle Walk Test at baseline was about 328 meters for 224 individuals and 389 m for 193 individuals at follow-up. At 3 months, the mean change in distance compared with baseline was 83 m in the intervention group (n = 94) and 47 m in the control group (n = 98; adjusted mean difference, 36.5 meters; 95% CI, 6.6–66.3 meters; P = .02). Critically, there were no significant interactions on the primary outcome analysis by sex, race, clinical presentation group, or time of symptom onset.¹

There were greater improvements in the intervention group versus the control group in health-related quality of life utility score at 2 months post-randomization (0.06; 95% CI, 0.01–0.11; P = .02), the 4-item Patient Health Questionnaire (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), according to the study authors. Importantly, there were minimal adverse events reported, and no deaths occurred in the intervention.¹

Pharmacists can proactively integrate resistance exercise counseling into their patient interactions in the respiratory disease setting, especially regarding COVID-19 and long COVID. Exercise is known to widely benefit an individual’s health system in numerous areas, and this research highlights its role in improving the physical and physiological capabilities of patients struggling with prolonged COVID-19 symptoms.¹

“This pragmatic intervention may be a generalizable therapy for individuals with persisting physical symptoms after COVID-19 infection,” the study authors concluded.¹

REFERENCES

1. Berry C, McKinley G, Bayes HK, et al. Resistance exercise therapy after COVID-19 infection: A randomized clinical trial. JAMA Netw Open. 2025;8(11):e2534304. doi:10.1001/jamanetworkopen.2025.34304

2. CISCO-21 prevent and treat long COVID-19 (CISCO-21). ClinicalTrials.gov Identifier: NCT04900961. Last Updated February 25, 2025. Accessed December 2, 2025. https://clinicaltrials.gov/study/NCT04900961

3. Ely EW, Brown LM, Fineberg HV, et al. Long covid defined. N Engl J Med. 2024;391(18):1746-1753. doi:10.1056/NEJMsb2408466

4. Rooney S, Webster A, Paul L. Systematic review of changes and recovery in physical function and fitness after severe acute respiratory syndrome—related coronavirus infection: Implications for COVID-19 rehabilitation. Physical Therapy. 2020;100(10):1717-1729. doi.org/10.1093/ptj/pzaa129

5. Finnigan LCEM, Cassar MP, Jafarpour M, et al. ¹H and ³¹P MR spectroscopy to assess muscle mitochondrial dysfunction in long COVID. Radiology. 2024;313(3). doi:10.1148/radiol.233173

6. Pouliopoulou DV, Macdermid JC, Saunders E, et al. Rehabilitation interventions for physical capacity and quality of life in adults with post-COVID-19 condition: A systematic review and meta-analysis. JAMA Netw Open. 2023;6(9):e2333838. doi:10.1001/jamanetworkopen.2023.33838