Dyspnea and fatigue in Long-COVID: definition of risk factors and of DLCO-based phenotypes in a multicenter study of 765 patients from Italy.

BACKGROUND: Dyspnea and fatigue represent common Long-COVID symptoms, but their presence is not always accompanied by lung function abnormalities. Aim of the study was to evaluate dyspnea and fatigue in relation to pulmonary function and exercise capacity. METHODS: Multicenter cohort study. Multivariable analyses were used to characterize, for both symptoms, functional phenotypes with and without pulmonary impairment according to the diffusing lung capacity for carbon monoxide (DLCO). Exercise capacity was assessed through the distance walked in 6 minutes (6MWD). RESULTS: Among 765 patients evaluated at a mean interval of six months from COVID-19, rates of dyspnea and fatigue were 41.3% and 41.6%, respectively. Roughly half of the patients with these two symptoms (51.6% and 54.7%, respectively) had normal pulmonary function at DLCO testing (≥80% of predicted). Low-DLCO (<80%) dyspnea was significantly associated with female sex, anxiety, duration of hospitalisation, use of corticosteroids and of monoclonal neutralizing antibodies, and its risk decreased at the increasing in time from acute infection. Normal-DLCO dyspnea was associated with younger age and obesity. Low-DLCO fatigue was associated with female sex, heart failure, anxiety and use of corticosteroids. Normal-DLCO fatigue was not associated with demographics, comorbidities, or COVID-19 severity. For both symptoms, the low-DLCO phenotypes had a significantly lower 6MWD. CONCLUSIONS: The clinical phenotypes of dyspnea and fatigue with normal pulmonary function should be further explored, possibly with additional tests that assess cardiorespiratory and cardiovascular function. DLCO testing should be included in the evaluation of patients who report dyspnea and/or fatigue as possible Long-COVID symptoms.