UCSF Researchers Use Advanced Cardiopulmonary and Biomarker Testing to Assess Reduced Exercise Tolerance and Symptoms

While some patients recover from the effects of SARS-CoV-2 infection, others have experienced the aftereffects of COVID-19 long after the initial infection. One of these long COVID symptoms is reduced exercise capacity. But questions remain about the mechanisms underlying why some COVID patients continue to experience diminished exercise capacity while others recover without this condition.

In a study published in the Journal of Infectious Diseases, a team of researchers from UC San Francisco 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 sub-study as part of the Long-Term Impact of Infection with Novel Coronavirus (LIINC) study which was 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 to evaluate cardiac conditions underlying post-COVID 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 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% percent 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 myalgic encephalitis/chronic fatigue syndrome.

“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.}

_{About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is a top-ranked specialty hospital, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland, Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit https://ucsfhealth.org. Follow UCSF Health on Facebook or on Twitter.}

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