Distinctive Pseudopalisaded Histiocytic Hyperplasia Characterizes the Transition of Exudative to Proliferative Phase of Diffuse Alveolar Damage in Patients Dying of COVID-19

Kritselis, Michael; Yambayev, Ilyas; Prilutskiy, Andrey; Shevtsov, Artem; Vadlamudi, Charitha; Zheng, Hanqiao; Elsadwai, Murad; Ma, Lina; Aniskovich, Emily; Kataria, Yachana; Higgins, Sara; Sarita-Reyes, Carmen; Zuo, Tao; Zhao, Qing; Quillen, Karen; Burks, Eric J.

OBJECTIVES: Severe COVID-19 results in a glucocorticoid responsive form of acute respiratory distress (ARDS)/diffuse alveolar damage (DAD). Herein we compare the immunopathology of lung tissue procured at autopsy in patients dying of SARS-CoV-2 with those dying of DAD prior to the COVID-19 pandemic. METHODS: Autopsy gross and microscopic features stratified by duration of illness in twelve patients who tested positive for SARS-CoV-2 viral RNA as well as seven patients dying of DAD prior to the COVID-19 pandemic were evaluated with multiplex (5-plex: CD4, CD8, CD68, CD20, AE1/AE3) and SARS-CoV immunohistochemistry to characterize the immunopathologic stages of DAD. RESULTS: We observed a distinctive pseudopalisaded histiocytic hyperplasia interposed between the exudative and proliferative phase of COVID-19 associated DAD which was most pronounced at the fourth week from symptom onset. Pulmonary macrothrombi were seen predominantly in cases with pseudopalisaded histiocytic hyperplasia and/or proliferative phase DAD. Neither pseudopalisaded histiocytic hyperplasia nor pulmonary macrothrombi were seen in non-COVID-19 DAD cases, whereas microthrombi were common in DAD regardless of etiology. CONCLUSION: The inflammatory pattern of pseudopalisaded histiocytic hyperplasia may represent the distinctive immunopathology associated with the dexamethasone responsive form of DAD seen in severe COVID-19.