Interrogative approaches identify causes of physical impairment in those affected by post- COVID-19 morbidity (Long COVID) - an international multicenter observational study- Protocol).

Background The value of clinical cardiopulmonary exercise testing (CPET) within healthcare settings has been established in the last decade. CPET methods remain highly relevant in the COVID-19 endemic phase and should be used to assess those recovering from COVID-19 infection. This diagnostic tool could play an integral role in disease prognostication and evaluate the integrative response to incremental exercise. The primary aims of the study are to (1) evaluate the integrative response to incremental exercise relating to post-COVID-19 morbidity and (2) assess cardio-respiratory responses to physiological stress and provide insight regarding the integrity of the pulmonary-vascular interface and characterization of any impairment or abnormal cardio-respiratory function. Methods Participants will be asked to attend 3 lab visits, 1 baseline visit where they will provide patient reported outcome measures of symptomatology, Quality of Life, Sleep, Fatigue, Dyspnea and Cognition alongside assessments of lung function and functional capacity (six-minute walk test and timed up and go). Following a 7–10 observation period for post exertional malaise, patients will be asked to perform a cardiopulmonary exercise test on 2 consecutive days where their response to exercise will be quantified. A sub-sample will then report on post-CPET symptomology for seven consecutive dates using a bespoke smartphone application. Discussion Data from such assessments can enable practitioners to characterize cardio-respiratory fitness and identify reasons for physical impairment or abnormal cardio-respiratory function. measurements obtained from an assessment of cardio-respiratory responses to physiological stress could provide insight regarding the integrity of the pulmonary-vascular interface and characterisation of any impairment or abnormal cardio-respiratory function. Trial registration : Retrospectively Registered at Clinicaltrials.gov: NCT 06394921. Date of Registry: 26-03-2024.