Reduced exercise capacity in patients suffering from post-acute sequelae SARS-CoV-2 infection—otherwise known as Long COVID—is associated with cardiopulmonary symptoms, chronotropic incompetence, and earlier inflammatory markers, according to research results published in the Journal of Infectious Diseases.1
The research, which was led by investigators from the University of California San Francisco, was part of the Long-Term Impact of Infection with Novel Coronavirus (LIINC) study. The LIINC study started in November 2020 and was designed to evaluate both physical and mental health after an infection with COVID-19.
Although it is known that some patients with Long COVID present with cardiopulmonary symptoms, the underlying mechanisms for why this occurs remains unclear. Investigators conducted a sub-study of the initial LIINC study to examine cardiopulmonary mechanisms and reduced exercise capacity.
Protocol from the LIINC study was amended to conduct a second visit 1 year later for cross-sectional cardiopulmonary testing, including cardiopulmonary exercise testing, cardiac magnetic resonance imaging, and ambulatory rhythm monitoring.
The study cohort included 60 participants with a median age of 53, of which 42% were female and 87% were non-hospitalized. All of the patients were part of the initial LIINC study. Patients who completed an echocardiogram visit were eligible irrespective of symptoms. Participants completed interviews about medical history, acute infection, cardiopulmonary diagnoses, and symptoms.
The study’s primary case definition of symptoms included chest pain, dyspnea, palpitations, or fatigue in the 2 weeks preceding the study visit.
Investigators found that 49% of participants with symptoms had reduced exercise capacity on cardiopulmonary exercise testing compared to 16% of participants with no symptoms. Adjusted peak VO2 was 16.9% lower precent predicted among those with symptoms and a 5 ml/kg/min decrease was associated with 2.75 times higher odds of symptoms. Patients with symptoms also completed less work despite higher perceived effort and similar respiratory exchange ratio.
Additionally, chronotropic incompetence was highly associated with symptoms. Participants with chronotropic incompetence had 49 beats per minute lower peak heart rate compared to those with normal exercise capacity and chronotropy.
“The findings suggest that chronotropic incompetence—failure to achieve 80% of expected maximum heart rate while exercising—contributes to exercise limitations in Long COVID,” said Matthew Durstenfeld, lead author on the study and an assistant professor of Medicine at UC San Francisco. “We also found evidence of EBV reactivation in all individuals with chronotropic incompetence, however, we found no evidence of myocarditis, cardiac dysfunction, or clinically significant arrhythmias.”
The study builds on previous research that has reported reduced exercise capacity in patients with Long COVID by measuring exercise capacity later after an infection. The investigators noted that translational and proof-of-concept clinical research to determine underlying mechanisms of Long COVID is urgently needed to identify potential therapies.
Limitations of the study include small sample size, non-probabilistic sampling, cross-sectional measures, and volunteer bias that may have resulted in overestimated prevalence of reduced exercise capacity.
“Although exercise is unlikely to cure Long COVID, preliminary data suggest that exercise training is the only intervention demonstrated to improve exercise capacity, symptoms and quality of life,” said Durstenfeld. “Given patient concerns that exercise may worsen symptoms for some people, we need to rigorously study the role of exercise in Long COVID.”
1. Durstenfeld MS, Peluso MJ, Kaveti P, et al. Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID. The J Infect Dis. 2023;jiad131. https://doi.org/10.1093/infdis/jiad131.