1. The gastrointestinal tract is an alternative route for SARS-CoV-2 infection in a nonhuman primate model
- Author
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Junbin Wang, Siwen Zhao, Haixuan Wang, Jingmei Li, Jing Yang, Jiansheng Liu, Jiahong Gao, Yuan Zhao, Kaiyun Ding, Wenhai Yu, Haiyan Li, Mengli Yang, Haiting Long, Chunxia Ma, Shuaiyao Lu, Hongqi Liu, Dexuan Kuang, Daoju Wu, Yun Yang, Jingwen Xu, Li Jiao, and Xiaozhong Peng
- Subjects
viruses ,SARS-CoV-2, severe acute respiratory syndrome CoV-2 ,DMEM, Dulbecco’s modified Eagle’s medium ,Pathogenesis ,Random Allocation ,Feces ,Intestine, Small ,Respiratory system ,skin and connective tissue diseases ,Lung ,IEC, intestinal epithelial cells ,Gastrointestinal tract ,ACE2, angiotensin converting enzyme 2 ,Caspase 3 ,NHP, non-human primate ,HE, hematoxylin and eosin ,Gastroenterology ,virus diseases ,Inflammatory cytokines ,GI, gastrointestinal ,Gastroenteritis ,Trachea ,medicine.anatomical_structure ,COVID-19 Nucleic Acid Testing ,COVID-19, Coronavirus Disease 2019 ,Cytokines ,RNA, Viral ,Tumor necrosis factor alpha ,Goblet Cells ,medicine.symptom ,TMPRSS2, type II transmembrane serine protease ,IHC, immunohistochemistry ,Primates ,qRT-PCR, quantitative reverse transcription polymerase chain reaction ,Inflammation ,Bronchi ,Fecal-oral route ,FFPE, Formalin-Fixed Paraffin-Embedded ,Article ,Proinflammatory cytokine ,FBS, fetal bovine serum ,medicine ,Animals ,Humans ,pfu, plaque-forming units ,Hepatology ,business.industry ,SARS-CoV-2 ,fungi ,Rectum ,COVID-19 ,medicine.disease ,Macaca mulatta ,respiratory tract diseases ,Gastrointestinal Tract ,Pneumonia ,Disease Models, Animal ,Nasal Mucosa ,Ki-67 Antigen ,AB-PAS, Alcian blue and periodic acid-Schiff ,Gastric Mucosa ,Viral infection ,Immunology ,business - 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., Graphical abstract
- Published
- 2020