Exercise capacity was reduced more than 3 months after SARS-CoV-2 infection among patients with symptoms consistent with long COVID-19 (LC) compared with those without LC symptoms, according to a study in JAMA Network Open.

A systematic review and meta-analysis sought to determine whether adults with persistent COVID-19 symptoms more than 3 months after SARS-CoV-2 infection have reduced exercise capacity on cardiopulmonary exercise testing (CPET) compared with recovered individuals without symptoms, as well as to identify potential causal pathways for the lowered exercise capacity.

Investigators conducted a literature search on December 20, 2021, and on May 24, 2022. Eligible studies reported CPET measurement of peak V̇O2 in adults at least 3 months after SARS-CoV-2 infection.

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The study authors selected 41 reports of 38 observational studies in which CPET was performed in 2160 patients, including 1228 individuals with symptoms consistent with LC. Of the studies, 32 (84.2%) were single-center case series of patients who attended LC clinics or were referred for clinical CPET (symptomatic individuals) or cross-sectional assessments within COVID-19 recovery groups (with and without current symptoms).

A total of 9 studies included individuals with prevalent symptoms (n=464) and recovered individuals without prevalent symptoms (n=359). According to a meta-analysis of this group of studies, the mean peak V̇O2 was estimated to be -4.9 (95% CI, -6.4 to -3.4) mL/kg/min in patients with symptoms (P <.001). Subgroup analyses according to the proportion of patients hospitalized or time after SARS-CoV-2 infection were not significantly different.

The analysis also included 37 studies with at least 714 individuals who had reduced exercise capacity that classified patterns or limitations or assessed specific mechanisms, with most studies defining decreased exercise capacity as less than 80% or less than 85% of predicted levels. Deconditioning was the most frequent pattern in 10 studies, with alterations in muscular oxygen use noted as an alternative explanation. Muscular and/or peripheral oxygen extraction abnormalities also were common. Dysfunctional breathing, hyperventilation, or ventilatory inefficiency also were reported.

Among several limitations, the literature search was not limited to peer-reviewed studies. In addition, many studies were case series, which contributed only to classification of exercise limitations. Also, owing to selection bias, the prevalence of reduced exercise capacity could not be estimated, and moderate heterogeneity was observed in the studies.

“In this meta-analysis and systematic review, we found evidence that exercise capacity is reduced after SARS-CoV-2 infection among individuals who have symptoms consistent with LC, with a low confidence in the effect size,” stated the researchers. “Interventional trials of potential therapies are urgently needed, including studies of rehabilitation to address deconditioning, as well as further mechanistic investigation into dysfunctional breathing, autonomic dysfunction, chronotropic incompetence, impaired oxygen uptake or utilization, and preload failure to identify treatments for LC.”

Disclosures: Some of study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Durstenfeld MS, Sun K, Tahir P, et al. Use of cardiopulmonary exercise testing to evaluate long COVID-19 symptoms in adults: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(10):e2236057. doi:10.1001/jamanetworkopen.2022.36057

This article originally appeared on Pulmonology Advisor