Abstract
BACKGROUND: Atypical presentation of coronavirus disease-19 (COVID-19) from classic acute respiratory distress syndrome needs to be extensively evaluated to understand the pathophysiology to optimize the management protocol for severely ill patients to abrogate the terminal event. METHODS: Autopsy core needle biopsies of lungs were obtained from 12 patients who died with COVID-19. Routine histopathological examination of lung tissue along with immunohistochemical analysis of C4d complement staining was studied. Formalin-fixed paraffin-embedded biopsy material was also subjected to real-time reverse transcription-polymerase chain reaction for severe acute respiratory syndrome - coronavirus (SARS-CoV2) gene. RESULTS: In the study, all the deceased patients were symptomatic with two-thirds suffering from isolated SARS-CoV2-related pneumonia while remaining one-third had secondary COVID-19 infection. Histopathological evaluation highlights diffuse alveolar damage as the predominant pattern; however, complement-mediated endothelial injury of septal microvasculature, and microthrombi was also distinctly observed with increased serum levels of D-Dimer and fibrinogen-degradation products. The patients who had extrapulmonary manifestations at the time of presentation also showed pulmonary vascular lesions on histopathologic examination. Our study confirms the presence of coagulopathy and immune-mediated microthrombi in pulmonary septal microvasculature in patients with severe disease. CONCLUSION: The results of our small series of patients highlight the possibility of immune-mediated pulmonary vascular injury and thrombosis which has the potential to evolve into large vessel thrombosis and pulmonary embolism in critically ill patients. Definitive therapeutic management protocol including thromboembolic prophylaxis and development of effective immune-modulatory target could possibly reduce mortality in severely ill patients.