Cardiopulmonary exercise testing in COVID-19 patients at 3 months follow-up☆

Background: Long-term effects of Coronavirus Disease of 2019 (COVID-19) are of utmost relevance. We aimed to determine: 1) the functional capacity of COVID-19 survivors by cardiopulmonary exercise testing (CPET); 2) the characteristics associated with cardiopulmonary exercise testing (CPET) performance; 3) the safety and tolerability of CPET. Methods: We prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 from Azienda Sanitaria Locale 3, Genoa. Three months after hospital discharge a complete clinical evaluation, trans-thoracic echocardiography, CPET, pulmonary function tests, and dominant leg extension (DLE) maximal strength measurement were performed. Results: From the 225 patients discharged alive from March to November 2020, we excluded 12 incomplete/ missing cases and 13 unable to perform CPET, leading to a final cohort of 200. Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3-103.1). Ninety-nine (49.5%) patients had %pVO2 below, whereas 101 (50.5%) above the 85% predicted value. Among the 99 patients with reduced %pVO2, 61 (61%) had a normal anaerobic threshold: of these, 9(14.8%) had respiratory, 21(34.4%) cardiac, and 31(50.8%) non-cardiopulmonary reasons for exercise limitation. Inerestingly, 80% of patients experienced at least one disabling symtpom, not related to %pVO2 or functional capacity. Multivariate linear regression showed percent-predicted forced expiratory volume in one-second(beta = 5.29,p = 0.023), percent-predicted diffusing capacity of lungs for carbon monoxide(beta = 6.31,p = 0.001), and DLE maximal strength(beta = 14.09,p = 0.008) to be independently associated with pVO2. No adverse event was reported during or after CPET, and no involved health professional developed COVID-19. Conclusions: At three months after discharge, about 1/3rd of COVID-19 survivors show functional limitations, mainly explained by muscular impairment, calling for future research to identify patients at higher risk of longterm effects that may benefit from careful surveillance and targeted rehabilitation.