期刊
CELL RESEARCH
卷 31, 期 8, 页码 836-846出版社
SPRINGERNATURE
DOI: 10.1038/s41422-021-00523-8
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资金
- Chongqing Science and Technology Commission [cstc2020jscx-fyzxX0037]
- Chongqing Health Committee [2020NCPZX01]
- Third Military Medical University [2020XGBD08]
The study profiles 26 COVID-19 autopsy cases from Wuhan and determines the systemic distribution of SARS-CoV-2 in critically ill patients. It reveals that SARS-CoV-2 may invade multiple organs and utilize physiological barriers as entry ports for systemic dissemination, shedding light on novel COVID-19 treatment development.
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.
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