An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (T(I)) during the tidal volume (V(T)) to the total breath duration (T(I)/T(TOT)) and by the V(T)/T(I) ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed T(I)/T(TOT) and V(T)/T(I) at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O(2) uptake (VO(2)peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of T(I)/T(TOT) at rest and at peak, and lower values in V(T)/T(I) at peak (p < 0.05). In LC patients, values of T(I)/T(TOT) at peak were significantly related to ∆PETCO(2), i.e., the end-tidal pressure of CO(2) at peak minus the one at rest (p < 0.05). When LC patients were categorized by the T(I)/T(TOT) 0.38 cut-off value, patients with T(I)/T(TOT) > 0.38 showed lower values in VO(2)peak and maximal workload, and greater values in the ventilation/CO(2) linear relationship slope than patients with T(I)/T(TOT) ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.