Alternative complement pathway regulation of beta cell homeostasis

项目总结/摘要 2019年冠状病毒病（COVID-19）是一种全球性大流行病， 截至2020年5月底，确诊病例已超过560万例。数量 在我国，病例数接近170万，死亡人数超过10万。内 在美国，COVID-19的流行存在巨大的区域差异， 纽约州，特别是纽约市市区受到的打击尤为严重。 不良结局的人口统计学风险因素，例如需要机械 在COVID-19的通气和死亡率包括糖尿病和肥胖。高血糖 COVID-19与不良结局相关;然而，高血糖的机制 仍然未知。新的证据表明，SARS-CoV-2可以感染细胞外 鼻咽和肺的组织ACE 2是SARS-CoV-2的共受体， 包括β细胞。我们假设SARS-CoV-2直接 感染β细胞引起β细胞功能障碍和急性高血糖症。我们建议 明确COVID-19患者高血糖的生理机制， 一个大型生物样本库的样本了解高血糖的机制可能 转化为可能改善COVID-19患者护理的临床治疗。

Project Summary/Abstract Coronavirus disease of 2019 (COVID-19) is a worldwide pandemic that quickly grew from the end of 2019 to more than 5.6 million confirmed cases as of late May 2020. The number of cases is approaching 1.7 million with over 100,000 deaths in our country. Within the United States, there is tremendous regional variability in the prevalence of COVID-19 with New 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 mechanical ventilation and mortality in COVID-19 include diabetes and obesity. Hyperglycemia in COVID-19 is associated with poor outcomes; however, the mechanism for hyperglycemia remains unknown. Emerging evidence show that SARS-CoV-2 could infect cells outside of the nasopharynx and lungs. ACE2 is a coreceptor for SARS-CoV-2 and is expressed on pancreatic islet cells, including beta cells. We hypothesize that SARS-CoV-2 directly infects beta cells to cause beta cell dysfunction and acute hyperglycemia. We propose to define the physiological mechanism of hyperglycemia in COVID-19 patients assessing samples from a large biobank. Understanding the mechanism for hyperglycemia may translate into clinical treatments that may improve care of COVID-19 patients.