Volume 31, No 8, Aug 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 8, August 2021: 836-846   |  Open Access

ORIGINAL ARTICLES

A cohort autopsy study defines COVID-19 systemic pathogenesis

Xiao-Hong Yao^1,2 , Tao Luo^1,2 , Yu Shi^1,2 , Zhi-Cheng He^1,2 , Rui Tang^1,2 , Pei-Pei Zhang^3,4 , Jun Cai⁵ , Xiang-Dong Zhou⁶ , Dong-Po Jiang⁷ , Xiao-Chun Fei⁴ , Xue-Quan Huang⁸ , Lei Zhao⁵ , Heng Zhang⁴ , Hai-Bo Wu³ , Yong Ren⁹ , Zhen-Hua Liu¹⁰ , Hua-Rong Zhang^1,2 , Cong Chen^1,2 , Wen-Juan Fu^1,2 , Heng Li³ , Xin-Yi Xia¹¹ , Rong Chen¹² , Yan Wang^1,2 , Xin-Dong Liu^1,2 , Chang-Lin Yin¹³ , Ze-Xuan Yan^1,2 , Juan Wang¹⁴ , Rui Jing¹⁵ , Tai-Sheng Li¹⁶ , Wei-Qin Li¹⁷ , Chao-Fu Wang⁴ , Yan-Qing Ding¹⁸ , Qing Mao¹⁹ , Ding-Yu Zhang¹² , Shu-Yang Zhang^20,* , Yi-Fang Ping^1,2,* , Xiu-Wu Bian^1,2,3,*

¹Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
²Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China
³Department of Pathology, the First Hospital Affiliated to University of Science & Technology of China, Hefei, Anhui, China
⁴Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
⁵Department of Pathology, School of Medicine, Shanghai Jiaotong University, Shanghai, China
⁶Department of Pulmonary & Critical Care Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
⁷Wound Trauma Medical Center, State Key Laboratory of Trauma, Daping Hospital, Third Military Medical University, Chongqing, China
⁸Department of Vascular Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
⁹Department of Pathology, General Hospital of Central Theater Command of PLA, Wuhan, Hubei, China
¹⁰Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
¹¹Institute of Laboratory Medicine, Jinling Hospital, School of Medicine, Nanjing University, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, China
¹²Wuhan Jinyintan Hospital (Wuhan Hospital for Infectious Diseases), Wuhan, Hubei, China
¹³Department of Critical Care Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
¹⁴Emergency Department and Clinical Skills Training Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
¹⁵Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
¹⁶Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China
¹⁷Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, China
¹⁸Department of Pathology, Nan Fang Hospital, Southern Medical University, Guangzhou, Guangdong, China
¹⁹Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
²⁰Peking Union Medical College Hospital, Beijing, China
These authors contributed equally: Xiao-Hong Yao, Tao Luo, Yu Shi, Zhi-Cheng He, Rui Tang, Pei-Pei Zhang These authors jointly supervised this work: Jun Cai, Xiang-Dong Zhou, Dong-Po Jiang, Xiao-Chun Fei, Xue-Quan Huang, Chao-Fu Wang, Yan-Qing Ding, Qing Mao, Ding-Yu Zhang Correspondence: Shu-Yang Zhang(shuyangzhang103@163.com)Yi-Fang Ping(pingyifang@126.com)Xiu-Wu Bian(bianxiuwu@263.net)

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.

https://doi.org/10.1038/s41422-021-00523-8

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