Histopathological manifestations of acute DAD and variable fibrotic abnormalities in COVID-19.
In comparison of lung autopsy samples of 8 COVID-19 patients and 6 non-COVID-19 patients, progressive pathologic changes, including diffuse alveolar damage (DAD), fibrosing organizing pneumonia, were evaluated(Figure 1A, B and Table 2) . DAD was found in all 8/8 COVID-19 patients with major characteristic features of widespread alveolitis (Figure S1A), sloughing of the bronchiolar epithelium(Figure S1B), formation of a hyaline membrane, (4/8) of cases(Figure S1C), and Intra-alveolar edema (5/8) cases(Figure S1D) . Interestingly, lung fibrosis exhibited a variable degree of abnormal features in all COVID-19 patients. The onset of fibrotic changes appeared focally in the alveolar interstitium with increased deposition of collagenous fibers (Figure 1C) . Mild to moderate interstitial fibrosis was present in 3/8 cases, while intra-alveolar fibrosis was noted in all except 2 cases (Figure 1D) . In 5/8 cases, organizing fibrosis was evident, with fibrosis extending into the surrounding parenchyma, thus causing disorganization of alveolar architecture and loss of air spaces (Figure 1E) . The loose myxoid fibroblastic proliferation extended between the alveoli in an intercommunicating manner, at places forming Masson bodies in alveolar and bronchiolar regions (Figure 1F) . Formation of bronchiolitis obliterans organizing pneumonia (BOOP) was noted in one case (Figure 1G). The squamous cells formed distinct nodules resembling squamous morules (Figure 1H) . Fibrotic changes also appear in the perivascular regions with pulmonary blood vessels surrounded by loosely organized proliferating fibroblasts(Figure 1I) . One specimen showed evidence of high inflammation in the pleura (Figure S1E) .In two cases, a superimposed bacterial infection was present, which was characterized by the presence of bacterial colonies admixed with neutrophils within the alveoli(Figure S1F) . Vascular thrombi in the small vessels were observed in 6/8 cases (Figure S1G) .