Quantitative CT Metrics Associated with Variability in the Diffusion Capacity of the Lung of Post-COVID-19 Patients with Minimal Residual Lung Lesions

(1) Background: A reduction in the diffusion capacity of the lung for carbon monoxide is a prevalent longer-term consequence of COVID-19 infection. In patients who have zero or minimal residual radiological abnormalities in the lungs, it has been debated whether the cause was mainly due to a reduced alveolar volume or involved diffuse interstitial or vascular abnormalities. (2) Methods: We performed a cross-sectional study of 45 patients with either zero or minimal residual lesions in the lungs (total volume < 7 cc) at two months to one year post COVID-19 infection. There was considerable variability in the diffusion capacity of the lung for carbon monoxide, with 27% of the patients at less than 80% of the predicted reference. We investigated a set of independent variables that may affect the diffusion capacity of the lung, including demographic, pulmonary physiology and CT (computed tomography)-derived variables of vascular volume, parenchymal density and residual lesion volume. (3) Results: The leading three variables that contributed to the variability in the diffusion capacity of the lung for carbon monoxide were the alveolar volume, determined via pulmonary function tests, the blood vessel volume fraction, determined via CT, and the parenchymal radiodensity, also determined via CT. These factors explained 49% of the variance of the diffusion capacity, with p values of 0.031, 0.005 and 0.018, respectively, after adjusting for confounders. A multiple-regression model combining these three variables fit the measured values of the diffusion capacity, with R = 0.70 and p < 0.001. (4) Conclusions: The results are consistent with the notion that in some post-COVID-19 patients, after their pulmonary lesions resolve, diffuse changes in the vascular and parenchymal structures, in addition to a low alveolar volume, could be contributors to a lingering low diffusion capacity.