Reduced Exercise Capacity, Chronotropic Incompetence, and Early Systemic Inflammation in Cardiopulmonary Phenotype Long Coronavirus Disease 2019

Background Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or "long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity. Methods We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers. Results Sixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted), compared with 3/19 (16%) without symptoms (P = .02). The adjusted peak oxygen consumption (VO2) was 5.2 mL/kg/min lower (95% confidence interval, 2.1-8.3; P = .001) or 16.9% lower percent predicted (4.3%-29.6%; P = .02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2. Late-gadolinium enhancement on CMR and arrhythmias were absent. Conclusions Cardiopulmonary symptoms >1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with "long COVID." Among individuals with cardiopulmonary long coronavirus disease 2019 (COVID-19) >1 year after severe acute respiratory syndrome coronavirus 2 infection, we found reduced exercise capacity compared with recovered individuals. Chronotropic incompetence (inadequate heart rate increase during exercise), early post-COVID inflammation, and Epstein-Barr virus reactivation may provide mechanistic clues. Key Points Long coronavirus disease 2019 symptoms were associated with reduced exercise capacity on cardiopulmonary exercise testing >1 year after severe acute respiratory syndrome coronavirus 2 infection. The most common abnormal finding was chronotropic incompetence. Reduced exercise capacity was associated with early elevations in inflammatory markers.