Browsing by Author "Petrillo, Mauro"
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- Gut as an alternative entry route for SARS-CoV-2: current evidence and uncertainties of productive enteric infection in COVID-19Publication . Clerbaux, Laure Alix; Mayasich, Sally A.; Munoz Pineiro, Amalia; Soares, Helena; Petrillo, Mauro; Albertini, Maria Cristina; Lanthier, Nicolas; Grenga, Lucia; Amorim, Maria JoãoThe gut has been proposed as a potential alternative entry route for SARS-CoV-2. This was mainly based on the high levels of SARS-CoV-2 receptor expressed in the gastrointestinal (GI) tract, the observations of GI disorders (such as diarrhea) in some COVID-19 patients and the detection of SARS-CoV-2 RNA in feces. However, the underlying mechanisms remain poorly understood. It has been proposed that SARS-CoV-2 can productively infect enterocytes, damaging the intestinal barrier and contributing to inflammatory response, which might lead to GI manifestations, including diarrhea. Here, we report a methodological approach to assess the evidence supporting the sequence of events driving SARS-CoV-2 enteric infection up to gut adverse outcomes. Exploring evidence permits to highlight knowledge gaps and current inconsistencies in the literature and to guide further research. Based on the current insights on SARS-CoV-2 intestinal infection and transmission, we then discuss the potential implication on clinical practice, including on long COVID. A better understanding of the GI implication in COVID-19 is still needed to improve disease management and could help identify innovative therapies or preventive actions targeting the GI tract.
- Mechanisms leading to gut dysbiosis in COVID-19: current evidence and uncertainties based on adverse outcome pathwaysPublication . Clerbaux, Laure Alix; Fillipovska, Julija; Muñoz, Amalia; Petrillo, Mauro; Coecke, Sandra; Amorim, Maria João; Grenga, LuciaAlteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis—notably for amino acid metabolism—leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.