Nonspecific Interstitial Pneumonia Pattern is a Frequent Finding in Patients with Post-Acute COVID-19 Syndrome Treated with Bilateral Orthotopic Lung Transplantation: Current Best Evidence

Patients with post-acute or long COVID-19 syndrome (PA-COVID) develop persistent symptoms and complications that last beyond 4 weeks of the initial infection. There is limited information regarding the pulmonary pathology in PA-COVID patients that require bilateral orthotopic lung transplantation (BOLT). Our experience with 40 lung explants from 20 PA-COVID patients that underwent BOLT is described. Clinico-pathologic findings are correlated with best evidence from literature. The lung parenchyma showed bronchiectasis (n=20) and severe interstitial fibrosis with areas resembling the nonspecific interstitial pneumonia (NSIP) pattern of fibrosis (n=20), interstitial fibrosis NOS (n=20) and fibrotic cysts (n=9). None of the explants exhibited a usual interstitial pneumonia (UIP) pattern of fibrosis. Other parenchymal changes included multinucleated giant cells (n=17), hemosiderosis (n=16), peribronchiolar metaplasia (n=19), obliterative bronchiolitis (n=6) and microscopic honeycombing (n=5). Vascular abnormalities included thrombosis of a lobar artery (n=1) and microscopic thrombi in small vessels (n=7). Systematic literature review identified 7 articles reporting the presence in 12 patients of interstitial fibrosis showing NSIP pattern (n=3), organizing pneumonia/diffuse alveolar damage (DAD) (n=4) and NOS (n=3) patterns. All but one of these studies also reported the presence of multinucleated giant cells and none of the studies reported the presence of severe vascular abnormalities. PA-COVID patients undergoing BOLT show a pattern of fibrosis that resembles mixed cellular-fibrotic NSIP pattern and generally lack severe vascular complications. As the NSIP pattern of fibrosis is often associated with autoimmune diseases, additional studies are needed to understand the mechanism of disease and learn whether this information can be used for therapeutic purposes.