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The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model.
Jiao, Li; Li, Haiyan; Xu, Jingwen; Yang, Mengli; Ma, Chunxia; Li, Jingmei; Zhao, Siwen; Wang, Haixuan; Yang, Yun; Yu, Wenhai; Wang, Junbin; Yang, Jing; Long, Haiting; Gao, Jiahong; Ding, Kaiyun; Wu, Daoju; Kuang, Dexuan; Zhao, Yuan; Liu, Jiansheng; Lu, Shuaiyao; Liu, Hongqi; Peng, Xiaozhong.
  • Jiao L; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Li H; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Xu J; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yang M; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Ma C; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Li J; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Zhao S; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Wang H; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yang Y; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yu W; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Wang J; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yang J; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Long H; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Gao J; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Ding K; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Wu D; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Kuang D; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Zhao Y; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Liu J; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Lu S; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China; State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Me
  • Liu H; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China. Electronic address: lhq@Imbcams.com.cn.
  • Peng X; National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China; State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Me
Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: covidwho-1065985
Semantic information from SemMedBD (by NLM)
1. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
2. Body tissue LOCATION_OF Vaccination
Subject
Body tissue
Predicate
LOCATION_OF
Object
Vaccination
3. 2019 novel coronavirus CAUSES Infection
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Infection
4. Schiff INHIBITS MKI67 gene|MKI67
Subject
Schiff
Predicate
INHIBITS
Object
MKI67 gene|MKI67
5. MKI67 gene|MKI67 STIMULATES caspase-3
Subject
MKI67 gene|MKI67
Predicate
STIMULATES
Object
caspase-3
6. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
7. Body tissue LOCATION_OF Vaccination
Subject
Body tissue
Predicate
LOCATION_OF
Object
Vaccination
8. 2019 novel coronavirus CAUSES Infection
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Infection
9. Schiff INHIBITS MKI67 gene|MKI67
Subject
Schiff
Predicate
INHIBITS
Object
MKI67 gene|MKI67
10. MKI67 gene|MKI67 STIMULATES caspase-3
Subject
MKI67 gene|MKI67
Predicate
STIMULATES
Object
caspase-3
ABSTRACT
BACKGROUND &

AIMS:

Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19.

METHODS:

Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity.

RESULTS:

Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections.

CONCLUSIONS:

Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Tract / Gastroenteritis / COVID-19 / Lung Type of study: Diagnostic study / Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal: Gastroenterology Year: 2021 Document Type: Article Affiliation country: J.gastro.2020.12.001

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gastrointestinal Tract / Gastroenteritis / COVID-19 / Lung Type of study: Diagnostic study / Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal: Gastroenterology Year: 2021 Document Type: Article Affiliation country: J.gastro.2020.12.001