Extensive pulmonary thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells as well as infected cell syncytia are hallmarks of advanced coronavirus disease 2019 (COVID-19) according to a study published in EBioMedicine. Virus-infected cells that persist for weeks after the initial diagnosis can play an important role in the symptoms and severity of COVID-19.
The study’s authors performed a post-mortem analysis of the lungs, brain, heart, liver and kidneys of 41 consecutive patients who had died of COVID-19 at the University Hospital in Trieste, Italy. Of these, 6 patients required an intensive care unit (IC). Immunohistochemical staining was performed on all tissue samples. In situ hybridization for the detection of the coronavirus 2 (SARS-CoV-2) genome of severe acute respiratory syndrome was performed in tissue samples from IC patients and 5 non-IC patients who met certain criteria.
At the start of the study, the most common comorbidities were high blood pressure (n = 17), chronic heart disease (n = 13), dementia (n = 13), diabetes (n = 12) and cancer (n = 12).
Of the 11 samples that were subjected to in situ hybridization, 10 showed numerous SARS-CoV-2 infected cells expressing viral spike protein in lung tissue. The results of the study showed extensive pulmonary vascular thrombosis in the micro and macro vasculature in 5 IC patients (83%) and 16 non-IC patients (46%). These thrombi showed different stages of organization, which indicates an endogenous, ongoing thrombotic process in the lungs.
A total of 29 patients (71%) in the study had sporadic pulmonary thrombosis and 10 patients (24%) had persistent vasculitis in the pulmonary microvasculature and macrovasculature. Dysmorphic cells, frequently showing syncytia, were present in pneumocytes from 20 patients (50%) including all 6 IC patients.
The presence of SARS-CoV-2 RNA in lung cells weeks after initial diagnosis calls into question the theory that COVID-19 follows a two-phase course, with an initial phase of virus replication followed by a second phase of hyperinflammation in which virus replication is less frequent is relevant.
“The presence of abundant cytoplasmic RNA signals and expression of the spike protein in the lungs 30 to 40 days after diagnosis in our study suggest continued replication and postulate a continued pathogenic role for viral infection,” the researchers noted. Other defining signs of COVID-19 were massive pulmonary thrombosis and endothelial dysfunction, and both were directly linked to the persistence of these virus-infected cells.
Bussani R., Schneider E., Zentilin L. et al. The persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of an advanced COVID-19 pathology. EBioMedicine. 2020; 61 (103104). doi: 10.1016 / j.ebiom.2020.103104
This article originally appeared on Infectious Disease Advisor