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.
Keywords: COVID-19; Fecal-Oral Route; Inflammatory Cytokines; Viral Infection.
【저자키워드】 COVID-19, viral infection, Inflammatory cytokines, Fecal-Oral Route, 【초록키워드】 coronavirus disease, SARS-CoV-2, Inflammation, immunohistochemistry, viral infection, Coronavirus disease 2019, coronavirus, Cytokines, Pathogenesis, macrophages, Pneumonia, SARS-COV-2 infection, Infection, lung, cytokine, severe acute respiratory syndrome Coronavirus, Histopathology, polymerase chain reaction, Viral, inoculation, response, Patient, Gastrointestinal, Clinical signs, reverse transcription, Inflammatory cytokines, mucin, respiratory, change, Quantitative, intranasal, GI Tract, Hypothesis, fecal, manifestation, host responses, Ki67, goblet cells, Chain Reaction, dysfunction, connection, acute respiratory syndrome, Rhesus monkeys, increased expression, acute respiratory syndrome coronavirus, tissue, acute respiratory syndrome coronavirus 2, tissues, severe infections, respiratory tissues, pathogenesis of COVID-19, viral genomic RNA, staining, CD68, rhesus, Clinical sign, pathogenesis of SARS-CoV-2, caspase 3, NHP, periodic acid, polymerase chain, were infected, caused, involved, reported, pathologic, investigated, evaluated, digestive, cleaved, increasingly, quantified, were recorded, respiratory tissue, 【제목키워드】 SARS-CoV-2, Model, Gastrointestinal, route, primate, tract,