Persistence of viral RNA, widespread thrombosis and abnormal cellular syncytia are hallmarks of COVID-19 lung pathology

COVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.