Alternative complement pathway regulation of beta cell homeostasis

Project Summary/Abstract: Coronavirus disease of 2019 (COVID-19) is a worldwide pandemic that quickly grew fromthe end of 2019 to more than 5.6 million confirmed cases as of late May 2020. The numberof cases is approaching 1.7 million with over 100,000 deaths in our country. Within theUnited States, there is tremendous regional variability in the prevalence of COVID-19 withNew York State and specifically the New York City metro area being particularly hard hit.The demographic risk factors for adverse outcomes such as need for mechanicalventilation and mortality in COVID-19 include diabetes and obesity. Hyperglycemia inCOVID-19 is associated with poor outcomes; however, the mechanism for hyperglycemiaremains unknown. Emerging evidence show that SARS-CoV-2 could infect cells outsideof the nasopharynx and lungs. ACE2 is a coreceptor for SARS-CoV-2 and is expressedon pancreatic islet cells, including beta cells. We hypothesize that SARS-CoV-2 directlyinfects beta cells to cause beta cell dysfunction and acute hyperglycemia. We propose todefine the physiological mechanism of hyperglycemia in COVID-19 patients assessingsamples from a large biobank. Understanding the mechanism for hyperglycemia maytranslate into clinical treatments that may improve care of COVID-19 patients.