Gastrointestinal Manifestations of SARS-CoV-2: Transmission, Pathogenesis, Immunomodulation, Microflora Dysbiosis, and Clinical Implications

Abstract

The clinical manifestation of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the respiratory system of humans is widely recognized. There is increasing evidence suggesting that SARS-CoV-2 possesses the capability to invade the gastrointestinal (GI) system, leading to the manifestation of symptoms such as vomiting, diarrhea, abdominal pain, and GI lesions. These symptoms subsequently contribute to the development of gastroenteritis and inflammatory bowel disease (IBD). Nevertheless, the pathophysiological mechanisms linking these GI symptoms to SARS-CoV-2 infection remain unelucidated. During infection, SARS-CoV-2 binds to angiotensin-converting enzyme 2 and other host proteases in the GI tract during the infection, possibly causing GI symptoms by damaging the intestinal barrier and stimulating inflammatory factor production, respectively. The symptoms of COVID-19-induced GI infection and IBD include intestinal inflammation, mucosal hyperpermeability, bacterial overgrowth, dysbiosis, and changes in blood and fecal metabolomics. Deciphering the pathogenesis of COVID-19 and understanding its exacerbation may provide insights into disease prognosis and pave the way for the discovery of potential novel targets for disease prevention or treatment. Besides the usual transmission routes, SARS-CoV-2 can also be transmitted via the feces of an infected person. Hence, it is crucial to implement preventive and control measures in order to mitigate the fecal-to-oral transmission of SARS-CoV-2. Within this context, the identification and diagnosis of GI tract symptoms during these infections assume significance as they facilitate early detection of the disease and the development of targeted therapeutics. The present review discusses the receptors, pathogenesis, and transmission of SARS-CoV-2, with a particular focus on the induction of gut immune responses, the influence of gut microbes, and potential therapeutic targets against COVID-19-induced GI infection and IBD.

COVID-19 Pandemic Modulates the Environmental Contamination Level with Enteric Bacteria from WWTPs

“…The binding of the virus to some proteases of the intestinal tract led to the production of inflammatory factors secondary to the viral infection that were potentially harmful to the intestinal barrier. The imbalances of the intestinal microbiota from secondary Covid-19 infections [23] have caused an increase in the number of hospitalized patients with both SARS-CoV-2 infections and secondary bacterial infections. A clinical research study from Romania demonstrated that both the number of hospitalized patients and the number of bacterial isolates was lower before the emergence and installation of the Covid-19 pandemic.…”

COVID-19 Pandemic Modulates the Environmental Contamination Level of Enteric Bacteria from WWTPs

“…The binding of the virus to some proteases in the intestinal tract led to the production of inflammatory factors secondary to the viral infection that were potentially harmful to the intestinal barrier. The imbalances of the intestinal microbiota from secondary COVID-19 infections [23] caused an increase in the number of hospitalized patients with both SARS-CoV-2 infections and secondary bacterial infections. A clinical research study from Romania demonstrated that both the number of hospitalized patients and the number of bacterial isolates was lower before the emergence and installation of the COVID-19 pandemic.…”

A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models

“…Healthy gut microbiome-induced cGAS-STING activation at a basal state in vivo 60 represents a particularly relevant context for our observations. SARS-CoV-2 can efficiently infect cells within infect gastrointestinal tract in vitro 103,104 , but it is possible that microbiota-induced activation of the cGAS-STING pathway can limit SARS-CoV-2 replication within the GI tract or its tropism within particular cell subsets therein. Interestingly, STING KO in K18-ACE2 mouse model did not appear to affect host defense and pathology 105 .…”