Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for critical COVID-19

Background Cardiopulmonary exercise testing (CPET) is an important clinical tool that provides a global assessment of the respiratory, circulatory and metabolic responses to exercise which are not adequately reflected through the measurement of individual organ system function at rest. In the context of critical COVID-19, CPET is an ideal approach for assessing long term sequalae. Methods In this prospective single-center study, we performed CPET in 60 patients, 12 months after a critical COVID-19 infection that required intensive care unit (ICU) treatment. Lung function at rest and chest computed tomography (CT) scan were also performed. Results Twelve months after severe COVID-19 pneumonia, the majority of the patients had a peak O2 uptake (V’O2) considered within normal limits. However, length of ICU stay remained an independent predictor of V’O2. Surprisingly, more than half of the patients with a normal peak predicted V’O2 showed ventilatory inefficiency during exercise (high VE/VCO2 ratio and high VE/VCO2 slope) with increased physiological dead space (VD/Vt) and low end-tidal CO2 partial pressure (PETCO2) values. This impairment was even more pronounced in patients with persistent dyspnea. Notably, peak VD/Vt values were positively correlated with peak D-Dimer plasma concentrations from blood samples collected during ICU stay. Conclusions Even if reduced exercise capacity was rare 12 months after critical COVID-19, more than half of the patients with normal exercise capacity showed ventilatory inefficiency. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04519320 ### Funding Statement This study was supported by a grant from the Don Du Souffle and from SOS Oxygene ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee (Comite de Protection des Personnes (CPP) Grand‐Est Ref 21 04 11) gave ethical approval for the protocol and written informed consent was obtained from all patients at the time of enrollment. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors