Decode the Impact of SARS-CoV-2 on Human Pancreas

Weill Medical Coll Of Cornell Univ, New York NY

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Linked publications & trials

Abstract

Abstract. Recent clinical data has suggested a bidirectional interaction between Coronavirus disease 19 (COVID-19) and diabetes. Individuals with diabetes and severe obesity are more likely to be complications, and have a higher COVID-19 mortality rate symptomatic . Conversely, new-onset diabetes and severe , are at a higher risk for metabolic complications of pre-existing diabetes have been observed in COVID-19 patients. Thus, there is a strong need to understand the pathology and mechanism of pancreatic dysfunction in COVID-19 patients. Here, we demonstrate the detection of SARS-CoV-2 in pancreatic endocrine cells in autopsy samples from COVID-19 patients. Single cell RNA-seq and immunostaining confirmed that multiple types of pancreatic islet cells are susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS- CoV-2 infection, beta cells show a decreased expression of insulin and the increased expression of alpha and acinar cell markers, including glucagon and PRSS1/trypsin1, respectively, suggesting cellular transdifferentiation. Hyperion technology to examine the pathogenesis of autopsy samples of COVID-19 patients. In addition, we will use human islets and a vascularized human pancreatic organoid models to systematically evaluate the role of direct infection and paracrine inflammation signal on human endocrine cells cellular identities, function and survival. In the proposal, we will apply state-of-art Through this study, we would expect to provide a systematic overview of the pathological changes in the pancreas of COVID-19 patients, as well as a detailed mechanism to understand endocrine cell dysfunction, which will pave the road to the development of novel therapy to protect endocrine cell function in COVID-19 patients.