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.