Persistence of lung structural and functional alterations at one year post‐COVID‐19 is associated with increased serum PD‐L2 levels and altered CD4/CD8 ratio

Background Persistent respiratory symptoms and lung abnormalities post‐COVID‐19 are public health problems. This study evaluated biomarkers to stratify high‐risk patients to the development or persistence of post‐COVID‐19 interstitial lung disease. Methods One hundred eighteen patients discharged with residual lung abnormalities compatible with interstitial lung disease (COVID‐ILD patients) after a severe COVID‐19 were followed for 1 year (post‐COVID‐ILD patients). Physical examination, pulmonary function tests, and chest high‐resolution computed tomography (HRCT) were performed. Soluble forms (s) of PD‐L1, PD‐L2, TIM‐3, and GAL‐9 were evaluated in serum and cell culture supernatant, as well as T‐cells subsets and the transmembrane expression of PD‐L1 and PD‐L2 on the cell surface. Results Eighty percent of the post‐COVID‐ILD patients normalized their lung function at 1‐year follow‐up, 8% presented COVID‐independent ILD, and 12% still showed functional and HRCT alterations. PD‐L2 levels were heterogeneous during acute COVID‐19 (aCOVID); patients who increased (at least 30%) their sPD‐L2 levels at 1 year post‐COVID‐19 and exhibited altered CD4/CD8 ratio showed persistence of chest tomographic and functional alterations. By contrast, patients who decreased sPD‐L2 displayed a complete lung recovery. sPD‐L1, sTIM‐3, and sGAL‐9 increased significantly during aCOVID and decreased in all patients after 1‐year follow‐up. Conclusion Increased sPD‐L2 and an altered CD4/CD8 ratio after 12 months of aCOVID are associated with the persistence of lung lesions, suggesting that they may contribute to lung damage post‐COVID‐19. Increased sPD‐L2 and an altered CD4/CD8 ratio after 12 months of acute COVID‐19 (aCOVID) are associated with the persistence of lung lesions. sPD‐L1 could be useful to improve the diagnosis during aCOVID.