Lung diffusing capacity for nitric oxide and carbon monoxide following mild‐to‐severe COVID‐19

A decreased lung diffusing capacity for carbon monoxide (DL(CO)) has been reported in a variable proportion of subjects over the first 3 months of recovery from severe coronavirus disease 2019 (COVID‐19). In this study, we investigated whether measurement of lung diffusing capacity for nitric oxide (DL(NO)) offers additional insights on the presence and mechanisms of gas transport abnormalities. In 94 subjects, recovering from mild‐to‐severe COVID‐19 pneumonia, we measured DL(NO) and DL(CO) between 10 and 266 days after each patient was tested negative for severe acute respiratory syndrome coronavirus 2. In 38 subjects, a chest computed tomography (CT) was available for semiquantitative analysis at six axial levels and automatic quantitative analysis of entire lungs. DL(NO) was abnormal in 57% of subjects, independent of time of lung function testing and severity of COVID‐19, whereas standard DL(CO) was reduced in only 20% and mostly within the first 3 months. These differences were not associated with changes of simultaneous DL(NO)/DL(CO) ratio, while DL(CO)/V(A) and DL(NO)/V(A) were within normal range or slightly decreased. DL(CO) but not DL(NO) positively correlated with recovery time and DL(CO) was within the normal range in about 90% of cases after 3 months, while DL(NO) was reduced in more than half of subjects. Both DL(NO) and DL(CO) inversely correlated with persisting CT ground glass opacities and mean lung attenuation, but these were more frequently associated with DL(NO) than DL(CO) decrease. These data show that an impairment of DL(NO) exceeding standard DL(CO) may be present during the recovery from COVID‐19, possibly due to loss of alveolar units with alveolar membrane damage, but relatively preserved capillary volume. Alterations of gas transport may be present even in subjects who had mild COVID‐19 pneumonia and no or minimal persisting CT abnormalities. TRIAL REGISTRY: ClinicalTrials.gov PRS: No.: NCT04610554 Unique Protocol ID: SARS‐CoV‐2_DLNO 2020.