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A cohort autopsy study defines COVID-19 systemic pathogenesis.
Yao, Xiao-Hong; Luo, Tao; Shi, Yu; He, Zhi-Cheng; Tang, Rui; Zhang, Pei-Pei; Cai, Jun; Zhou, Xiang-Dong; Jiang, Dong-Po; Fei, Xiao-Chun; Huang, Xue-Quan; Zhao, Lei; Zhang, Heng; Wu, Hai-Bo; Ren, Yong; Liu, Zhen-Hua; Zhang, Hua-Rong; Chen, Cong; Fu, Wen-Juan; Li, Heng; Xia, Xin-Yi; Chen, Rong; Wang, Yan; Liu, Xin-Dong; Yin, Chang-Lin; Yan, Ze-Xuan; Wang, Juan; Jing, Rui; Li, Tai-Sheng; Li, Wei-Qin; Wang, Chao-Fu; Ding, Yan-Qing; Mao, Qing; Zhang, Ding-Yu; Zhang, Shu-Yang; Ping, Yi-Fang; Bian, Xiu-Wu.
  • Yao XH; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Luo T; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Shi Y; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • He ZC; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Tang R; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Zhang PP; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Cai J; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Zhou XD; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Jiang DP; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Fei XC; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Huang XQ; Department of Pathology, the First Hospital Affiliated to University of Science & Technology of China, Hefei, Anhui, China.
  • Zhao L; Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • Zhang H; Department of Pathology, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • Wu HB; Department of Pulmonary & Critical Care Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Ren Y; Wound Trauma Medical Center, State Key Laboratory of Trauma, Daping Hospital, Third Military Medical University, Chongqing, China.
  • Liu ZH; Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • Zhang HR; Department of Vascular Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Chen C; Department of Pathology, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • Fu WJ; Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • Li H; Department of Pathology, the First Hospital Affiliated to University of Science & Technology of China, Hefei, Anhui, China.
  • Xia XY; Department of Pathology, General Hospital of Central Theater Command of PLA, Wuhan, Hubei, China.
  • Chen R; Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • Wang Y; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Liu XD; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Yin CL; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Yan ZX; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Wang J; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Jing R; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Li TS; Department of Pathology, the First Hospital Affiliated to University of Science & Technology of China, Hefei, Anhui, China.
  • Li WQ; Institute of Laboratory Medicine, Jinling Hospital, School of Medicine, Nanjing University, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, China.
  • Wang CF; Wuhan Jinyintan Hospital (Wuhan Hospital for Infectious Diseases), Wuhan, Hubei, China.
  • Ding YQ; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Mao Q; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Zhang DY; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Zhang SY; Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
  • Ping YF; Department of Critical Care Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • Bian XW; Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Cell Res ; 31(8): 836-846, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275907
Semantic information from SemMedBD (by NLM)
1. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
2. Lung PART_OF Patients
Subject
Lung
Predicate
PART_OF
Object
Patients
3. Organ PART_OF Patients
Subject
Organ
Predicate
PART_OF
Object
Patients
4. Lung LOCATION_OF 2019 novel coronavirus
Subject
Lung
Predicate
LOCATION_OF
Object
2019 novel coronavirus
5. Organ LOCATION_OF 2019 novel coronavirus
Subject
Organ
Predicate
LOCATION_OF
Object
2019 novel coronavirus
6. Endotheliu LOCATION_OF C5203676
Subject
Endotheliu
Predicate
LOCATION_OF
Object
C5203676
7. macrophage LOCATION_OF 2019 novel coronavirus
Subject
macrophage
Predicate
LOCATION_OF
Object
2019 novel coronavirus
8. Monocytes LOCATION_OF 2019 novel coronavirus
Subject
Monocytes
Predicate
LOCATION_OF
Object
2019 novel coronavirus
9. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
10. Lung LOCATION_OF Massive fibrosis
Subject
Lung
Predicate
LOCATION_OF
Object
Massive fibrosis
11. Lung LOCATION_OF Present
Subject
Lung
Predicate
LOCATION_OF
Object
Present
12. Lung LOCATION_OF Tissue injury
Subject
Lung
Predicate
LOCATION_OF
Object
Tissue injury
13. Organ LOCATION_OF Tissue injury
Subject
Organ
Predicate
LOCATION_OF
Object
Tissue injury
14. Organ LOCATION_OF Present
Subject
Organ
Predicate
LOCATION_OF
Object
Present
15. Present PROCESS_OF Patients
Subject
Present
Predicate
PROCESS_OF
Object
Patients
16. Tissue injury PROCESS_OF Patients
Subject
Tissue injury
Predicate
PROCESS_OF
Object
Patients
17. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
18. Lung PART_OF Patients
Subject
Lung
Predicate
PART_OF
Object
Patients
19. Organ PART_OF Patients
Subject
Organ
Predicate
PART_OF
Object
Patients
20. Lung LOCATION_OF 2019 novel coronavirus
Subject
Lung
Predicate
LOCATION_OF
Object
2019 novel coronavirus
21. Organ LOCATION_OF 2019 novel coronavirus
Subject
Organ
Predicate
LOCATION_OF
Object
2019 novel coronavirus
22. Endothelium, Vascular LOCATION_OF 2019 novel coronavirus
Subject
Endothelium, Vascular
Predicate
LOCATION_OF
Object
2019 novel coronavirus
23. macrophage LOCATION_OF 2019 novel coronavirus
Subject
macrophage
Predicate
LOCATION_OF
Object
2019 novel coronavirus
24. Monocytes LOCATION_OF 2019 novel coronavirus
Subject
Monocytes
Predicate
LOCATION_OF
Object
2019 novel coronavirus
25. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
26. Lung LOCATION_OF Massive fibrosis
Subject
Lung
Predicate
LOCATION_OF
Object
Massive fibrosis
27. Lung LOCATION_OF Present
Subject
Lung
Predicate
LOCATION_OF
Object
Present
28. Lung LOCATION_OF Tissue injury
Subject
Lung
Predicate
LOCATION_OF
Object
Tissue injury
29. Organ LOCATION_OF Tissue injury
Subject
Organ
Predicate
LOCATION_OF
Object
Tissue injury
30. Organ LOCATION_OF Present
Subject
Organ
Predicate
LOCATION_OF
Object
Present
31. Present PROCESS_OF Patients
Subject
Present
Predicate
PROCESS_OF
Object
Patients
32. Tissue injury PROCESS_OF Patients
Subject
Tissue injury
Predicate
PROCESS_OF
Object
Patients
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 / Lung Type of study: Etiology study / Incidence study / Observational study / Risk factors Topics: Long Covid Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: English Journal: Cell Res Year: 2021 Document Type: Article Affiliation country: S41422-021-00523-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 / Lung Type of study: Etiology study / Incidence study / Observational study / Risk factors Topics: Long Covid Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: English Journal: Cell Res Year: 2021 Document Type: Article Affiliation country: S41422-021-00523-8