Is Heart Rate Behind Exercise Difficulty in Long Covid Patients?

While some patients recover from the effects of COVID-19, others experience the aftereffects long after the initial infection. UC San Francisco researchers are studying why some COVID-19 patients experience prolonged symptoms, including diminished exercise capacity, while others recover.

In a study published May 11, 2023, in the Journal of Infectious Diseases, a team of UCSF researchers found that lower than expected exercise capacity was common among people with long COVID and chronotropic incompetence (inadequate heart rate increase during exercise) was the most common reason. They also found reduced exercise capacity to be correlated with early post-Covid elevations of inflammatory biomarkers. In addition, they found that reactivation of Epstein-Barr virus (EBV) may be related to reduced heart rate while exercising.

First author Matthew Durstenfeld, MD, MAS, designed the cardiovascular substudy as part of the Long-Term Impact of Infection with Novel Coronavirus (LIINC) study which was originally led by Michael Peluso, MD, MHS, UCSF assistant professor of Medicine. LIINC was designed to evaluate physical and mental health following COVID-19 infection by including individuals representing the full spectrum of acute illness and post-acute recovery. The study started in November 2020 using echocardiograms (a heart ultrasound) to evaluate cardiac conditions underlying post-COVID-19 symptoms.

When the initial echocardiogram-based study did not reveal cardiac mechanisms of symptoms, the team amended the study protocol to conduct a second visit with the study participants one year later for advanced testing including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory heart rhythm monitoring. Participants in the sub-study also had blood samples collected and processed for serum and plasma at their echocardiogram visit.

Sixty participants with a median age of 53 were studied at about a year and a half following COVID-19 infection. On CPET, 49% with symptoms had reduced exercise capacity compared to 16% without symptoms. Adjusted peak VO2 (the volume of oxygen the body consumes during exercise) was 16.9% lower than predicted among those with symptoms. Chronotropic incompetence was a common finding, and inflammatory biomarkers and antibody levels in the first few months after COVID-19 were negatively correlated with peak VO2 more than one year later.

“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 Durstenfeld, a cardiologist and UCSF assistant professor of Medicine. “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 authors note the clinical diagnostic challenge that patients with symptoms present when there are no objective findings of cardiac dysfunction on multimodality cardiopulmonary testing. They suggest translational and proof-of-concept clinical research to characterize distinct phenotypes and mechanisms of post-acute COVID symptoms is urgently needed to identify potential therapies.

Until additional therapies are available, the authors believe individuals living with reduced exercise capacity may benefit from exercise training to improve their symptoms. Patient advocates have raised important concerns about the safety of exercise in those with overlapping chronic fatigue syndrome-myalgic encephalitis.

“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.” 

Authors: Other UCSF authors include Michael J. Peluso, Punita Kaveti, Christopher Hill, Danny Li, Erica Sander, Shreya Swaminathan, Victor M. Arechiga, Scott Lu, Sarah A Goldberg, Rebecca Hoh, Ahmed Chenna, Brandon C. Yee, John W. Winslow, Christos J. Petropoulos, J. Daniel Kelly, David V. Glidden, Timothy J. Henrich, Jeffrey N. Martin, Yoo Jin Lee, Mandar A. Aras, Carlin S. Long, Donald J. Grandis, Steven G. Deeks, Priscilla Y. Hsue

Funding: This work was supported by US NIH/NLBI and NIH/NIAID grants and philanthropic gifts from Charles W. Swanson and the Ed and Pearl Fein Foundation. For other funding, see the study.

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