4.8 Article

The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model

期刊

GASTROENTEROLOGY
卷 160, 期 5, 页码 1647-1661

出版社

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2020.12.001

关键词

COVID-19; Viral Infection; Inflammatory Cytokines; Fecal-Oral Route

资金

  1. National Key R&D Project of China [2020YFA0707602, 2020YFC0846400, 2020YFC0841100]
  2. CAMS Innovation Fund for Medical Sciences [2016-I2M-2-001, 2016-I2M-2-006, 2020I2M-CoV19-012]
  3. Yunnan Key RD Project [202003AC100003]

向作者/读者索取更多资源

This study in a rhesus monkey model found that both intranasal and intragastric inoculation with SARS-CoV-2 led to pneumonia and gastrointestinal dysfunction, with inflammatory cytokines possibly playing a role in connecting the respiratory and digestive systems in disease pathogenesis.
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.

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