A meta-analysis suggested with low confidence that symptomatic long COVID was associated with decreased exercise capacity on cardiopulmonary exercise testing up to 3 months after initial SARS-COV-2 infection.

Underlying mechanisms may include but are not limited to deconditioning, peripheral mechanisms, hyperventilation, chronotropic incompetence, preload failure and autonomic and endothelial dysfunction, according to a study published in JAMA Network Open.

“In our meta-analysis of symptomatic vs. recovered individuals more than 3 months after SARS-CoV-2 infection, we found a modest but consistent effect suggesting that exercise capacity was reduced among individuals with long COVID, with very low certainty in the magnitude of the effect size by [the Grading of Recommendations, Assessment, Development, and Evaluations framework],” Matthew S. Durstenfeld, MD, MAS, assistant professor of medicine at the University of California, San Francisco, and noninvasive general cardiologist and physician-scientist clinical researcher at Zuckerberg San Francisco General Hospital, and colleagues wrote. “Despite the large number of participants included, the overall quality of the evidence is poor, owing to the small sample size of most studies, selection bias, variability in symptom ascertainment and cardiopulmonary exercise testing interpretation, inadequate methods to address confounding, and lack of appropriate statistical methods.”

For this meta-analysis, researchers identified 38 studies in which cardiopulmonary exercise testing was performed in individuals 3 to 18 months after SARS-CoV-2 infection.

Cardiopulmonary exercise testing involved measurement of baseline resting cardiopulmonary parameters, exercise on a cycle ergometer or a treadmill with measures of peak oxygen consumption (VO₂) and cardiopulmonary monitoring.

The primary outcome was change in exercise capacity defined as difference in peak VO₂ more than 3 months after initial SARS-CoV-2 infection among participants with and without symptoms of long COVID.

Among the 2,160 individuals included in this analysis, 1,228 had symptoms consistent with long COVID.

An analysis of nine studies including patients with and without symptoms of long COVID showed a mean change in peak VO₂ of 4.9 mL/kg/minute at 3 months among participants with long COVID symptoms (95% CI, 6.4 to 3.4; P < .001); however, moderate heterogeneity was observed.

Common symptoms included dyspnea, fatigue or exertional intolerance at the time of testing.

Using data from the cardiopulmonary exercise tests, the researchers concluded that mechanisms such as deconditioning, which may occur to some degree after any illness; peripheral mechanisms related to oxygen delivery and/or extraction; dysfunctional breathing or hyperventilation unexplained by baseline pulmonary tests; chronotropic incompetence; preload failure despite normal resting cardiac function; autonomic dysfunction; and endothelial dysfunction may be attributable to reduced exercise capacity in this population.

“Further research should include longitudinal assessments to understand the trajectory of exercise capacity,” the researchers wrote. “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 long COVID.”

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