tetano
Editor, Senior Moderator
Gastroenterology
. 2020 Dec 8;S0016-5085(20)35527-X.
doi: 10.1053/j.gastro.2020.12.001. Online ahead of print.
The gastrointestinal tract is an alternative route for SARS-CoV-2 infection in a nonhuman primate model
Li Jiao[SUP] 1 [/SUP], Haiyan Li[SUP] 1 [/SUP], Jingwen Xu[SUP] 1 [/SUP], Mengli Yang[SUP] 1 [/SUP], Chunxia Ma[SUP] 1 [/SUP], Jingmei Li[SUP] 1 [/SUP], Siwen Zhao[SUP] 1 [/SUP], Haixuan Wang[SUP] 1 [/SUP], Yun Yang[SUP] 1 [/SUP], Wenhai Yu[SUP] 1 [/SUP], Junbin Wang[SUP] 1 [/SUP], Jing Yang[SUP] 1 [/SUP], Haiting Long[SUP] 1 [/SUP], Jiahong Gao[SUP] 1 [/SUP], Kaiyun Ding[SUP] 1 [/SUP], Daoju Wu[SUP] 1 [/SUP], Dexuan Kuang[SUP] 1 [/SUP], Yuan Zhao[SUP] 1 [/SUP], Jiansheng Liu[SUP] 1 [/SUP], Shuaiyao Lu[SUP] 2 [/SUP], Hongqi Liu[SUP] 3 [/SUP], Xiaozhong Peng[SUP] 4 [/SUP]
Affiliations
Abstract
Background and aims: Gastrointestinal (GI) manifestations have been increasingly reported in Coronavirus Disease 2019 (COVID-19) patients. 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 (qRT-PCR). 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 pathological 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 (AB-PAS) staining showed decreased Ki67, increased cleaved caspase 3 and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these two 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.
Keywords: COVID-19; Fecal-oral route; Inflammatory cytokines; Viral infection.
. 2020 Dec 8;S0016-5085(20)35527-X.
doi: 10.1053/j.gastro.2020.12.001. Online ahead of print.
The gastrointestinal tract is an alternative route for SARS-CoV-2 infection in a nonhuman primate model
Li Jiao[SUP] 1 [/SUP], Haiyan Li[SUP] 1 [/SUP], Jingwen Xu[SUP] 1 [/SUP], Mengli Yang[SUP] 1 [/SUP], Chunxia Ma[SUP] 1 [/SUP], Jingmei Li[SUP] 1 [/SUP], Siwen Zhao[SUP] 1 [/SUP], Haixuan Wang[SUP] 1 [/SUP], Yun Yang[SUP] 1 [/SUP], Wenhai Yu[SUP] 1 [/SUP], Junbin Wang[SUP] 1 [/SUP], Jing Yang[SUP] 1 [/SUP], Haiting Long[SUP] 1 [/SUP], Jiahong Gao[SUP] 1 [/SUP], Kaiyun Ding[SUP] 1 [/SUP], Daoju Wu[SUP] 1 [/SUP], Dexuan Kuang[SUP] 1 [/SUP], Yuan Zhao[SUP] 1 [/SUP], Jiansheng Liu[SUP] 1 [/SUP], Shuaiyao Lu[SUP] 2 [/SUP], Hongqi Liu[SUP] 3 [/SUP], Xiaozhong Peng[SUP] 4 [/SUP]
Affiliations
- PMID: 33307034
- DOI: 10.1053/j.gastro.2020.12.001
Abstract
Background and aims: Gastrointestinal (GI) manifestations have been increasingly reported in Coronavirus Disease 2019 (COVID-19) patients. 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 (qRT-PCR). 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 pathological 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 (AB-PAS) staining showed decreased Ki67, increased cleaved caspase 3 and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these two 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.
Keywords: COVID-19; Fecal-oral route; Inflammatory cytokines; Viral infection.