Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/pathology , Lung/virology , Pneumonia, Viral/pathology , Aged , Alveolar Epithelial Cells/cytology , Alveolar Epithelial Cells/virology , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/virology , Female , Humans , Lung/pathology , Microscopy, Electron , Nasopharynx/virology , Nucleic Acids/genetics , Nucleic Acids/metabolism , Pandemics , Patient Discharge , Pneumonia, Viral/virology , SARS-CoV-2ABSTRACT
Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.