A cohort autopsy study defines COVID-19 systemic pathogenesis
Xiao-Hong Yao, Tao Luo, Yu Shi, Zhi-Cheng He, Rui Tang, Pei-Pei Zhang, Jun Cai, Xiang-Dong Zhou, Dong-Po Jiang, Xiao-Chun Fei, Xue-Quan Huang, Lei Zhao, Heng Zhang, Haibo Wu, Yong Ren, Zhen Hua Liu, Hua-Rong Zhang, Cong Chen, Wen-Juan Fu, Heng Li, Xin-Yi Xia, Rong Chen, Yan Wang, Xindong Liu, Chang-Lin Yin, Ze-Xuan Yan, Juan Wang, Rui Jing, Tai-Sheng Li, Wei-Qin Li, Chao‐Fu Wang, Yanqing Ding, Qing Mao, Ding-Yu Zhang, Shuyang Zhang, Yi‐Fang Ping, Xiu‐Wu Bian
Abstract
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.