Long-COVID Rehabilitation Interventions Improve Symptoms but Research on Safety Still Needed

A new systematic literature review and meta-analysis of studies using respiratory training and exercise-based rehabilitation for individuals with post-COVID condition (PCC), found moderate-certainty evidence that the interventions improved physical capacity and quality of life (QoL) when compared with standard care.

However, review authors also reported “a high level of uncertainty and imprecision” regarding the likelihood of exercise-induced adverse events, concluding that persons with PCC require close clinician monitoring during associated rehabilitation and that additional research is required on safety outcomes.

Writing in JAMA Network Open, the investigators cite a 2023 review that concluded improved outcomes for people with PCC are unlikely given the lack of high-quality research on optimal interventions. Current guidelines, they add, are based on observational data and expert opinion, creating a significant need for evidence-based recommendations. The most recent systematic review on the topic included just 3 trials.

Current guidelines are based on observational data and expert opinion, creating a significant need for evidence-based recommendations. The most recent systematic review on the topic included just 3 trials.

As the population affected by PCC continues to expand, research is becoming more robust, the research team wrote, allowing them to “conduct a more comprehensive, methodologically sound, and stable analysis.” And so, the purpose of their meta-analysis was to augment the available data on whether rehabilitation interventions are associated with improvements in physical capacity (functional exercise capacity, muscle function, dyspnea, and respiratory function) and quality of life in adults with PCC.”

Led by Dimitra V. Pouliopoulou, MSc, from the Faculty of Health Science’s School of Physical Therapy at Western University in Ontario, Canada, investigators searched MEDLINE, Scopus, CINAHL, and the Clinical Trials Registry for studies published between January 2020 and February 2023. Eligible Studies were randomized trials of individuals with PCC that compared rehabilitation interventions (eg, respiratory training and aerobic and resistance exercises) with a common comparison group identified as “control” (placebo, sham, waiting list, or usual care).

For the primary outcome, Pouliopoulou and colleagues were interested in participants’ capacity for functional exercise, assessed via 6-minute walking test at the closest post intervention time. They identified secondary outcomes as fatigue, lower limb muscle function, dyspnea, respiratory function, and QoL.

FINDINGS

Eligible randomized trials numbered 14, which included 1244 participants (median age 50 years; 45% women). Six trials included those who had been hospitalized for COVID-19; participants in 3 trials had not been hospitalized for their infection; and 5 trials included a mix of hospitalized and nonhospitalized participants.

The most common comparator to the specified rehabilitation interventions was usual care which most often took the form of respiratory training and exercise-based, self-management education; the most common limitations when usual care was unsupervised were incorrect use of equipment and poor execution of breathing techniques.

Overall, the research team reported, rehabilitation interventions for individuals affected by PCC were associated with a greater improvement in functional exercise capacity, dyspnea, and QoL compared with usual care. They found consistently that the interventions had a greater probability of superiority vs usual care across all of the outcomes, with a range between 85% and 99%. Rehabilitation programs also showed greater probability of reaching the minimum important difference threshold for functional aerobic capacity, functional lower limb strength, dyspnea, and QoL when compared with usual care; those probabilities ranged 84% and 95%.

Given the largely positive findings for the potential effects of structured rehabilitation after infection with COVID-19, the investigators end their results section stating that they did not find compelling evidence among the studies reviewed for a difference in the odds of adverse events.

Given the largely positive findings for the potential effects of structured rehabilitation after infection with COVID-19, the investigators end their results section stating that they did not find compelling evidence among the studies reviewed for a difference in the odds of adverse events.

The authors note that current treatment guidelines for PCC based on expert opinion suggest a supervised, individualized, symptom-based approach with close monitoring for adverse events such as orthostatic intolerance and postexertional symptom exacerbation but that "standard care" for these patients is still provided in the form of self-management recommendations in an ambulatory or home setting.

They point out that education-based, nonsupervised programs for people with chronic obstructive pulmonary disease are typically less effective than clinician-supervised ones. The significant uncertainty revealed in their meta-analysis regarding the probability of adverse events in the PCC rehabilitation program studied “further highlight the importance of supervised interventions with continuous monitoring and tailoring to ensure fidelity and patient safety until indicated otherwise.”

Source: 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