Persistent dyspnea after COVID-19 is not related to cardiopulmonary impairment; a cross-sectional study of persistently dyspneic COVID-19, non-dyspneic COVID-19 and controls

Background: Up to 53% of individuals who had mild COVID-19 experience symptoms for > 3-month following infection (Long-CoV). Dyspnea is reported in 60% of Long-CoV cases and may be secondary to impaired exercise capacity (VO2peak) as a result of pulmonary, pulmonary vascular, or cardiac insult. This study examined whether cardiopulmonary mechanisms could explain exertional dyspnea in Long-CoV.Methods: A cross-sectional study of participants with Long-CoV (n = 28, age 40 +/- 11 years, 214 +/- 85 days post-infection) and age- sex- and body mass index-matched COVID-19 naive controls (Con, n = 24, age 41 +/- 12 years) and participants fully recovered from COVID-19 (ns-CoV, n = 14, age 37 +/- 9 years, 198 +/- 89 days post-infection) was conducted. Participants self-reported symptoms and baseline dyspnea (modified Medical Research Council, mMRC, dyspnea grade), then underwent a comprehensive pulmonary function test, cardiopulmonary exercise test, exercise pulmonary diffusing capacity measurement, and rest and exercise echocardiography. Results: VO2peak, pulmonary function and cardiac/pulmonary vascular parameters were not impaired in Long- or ns-CoV compared to normative values (VO2peak: 106 +/- 25 and 107 +/- 25%(predicted), respectively) and cardiopulmonary responses to exercise were otherwise normal. When Long-CoV were stratified by clinical dyspnea severity (mMRC = 0 vs mMRC >= 1), there were no between-group differences in VO2peak. During submaximal exercise, dyspnea and ventilation were increased in the mMRC >= 1 group, despite normal operating lung volumes, arterial saturation, diffusing capacity and indicators of pulmonary vascular pressures. Interpretation: Persistent dyspnea after COVID-19 was not associated with overt cardiopulmonary impairment or exercise intolerance. Interventions focusing on dyspnea management may be appropriate for Long-CoV patients who report dyspnea without cardiopulmonary impairment.