Cellular and Molecular Mechanisms of COVID-19 Mediated Kidney Injury

项目总结/摘要 2019冠状病毒（COVID-19）大流行由严重急性呼吸系统综合征引起 冠状病毒2（SARS-CoV-2），并已导致超过100万例报告病例，显著的发病率和 死亡率，以及广泛的经济和社会破坏。这种疾病的发展 并发症肾衰竭越来越清楚的是，肾脏参与COVID-19的多种机制- 手术感染19例。30%至40%的严重感染的COVID-19患者发展为急性肾脏病 需要在重症监护室进行透析治疗的比例较高的损伤。此外，来自 活组织检查和尸检研究表明，肾足细胞、近端肾小管上皮细胞和内皮细胞 细胞可能会感染SARS-CoV-2。新数据表明，COVID-19足细胞损伤 导致肾病综合征，近端肾小管受累导致急性肾损伤， 参与导致血栓性微血管病-因此，COVID-19肾脏参与可能具有蛋白质变性， 临床表现，类似于HIV感染对肾脏的影响。没有具体的治疗方法 目前已验证用于COVID-19相关肾病，并了解细胞特异性分子 肾脏疾病和糖尿病患者与COVID-19相关的过程可能具有显著的 对公众健康的影响。更好地了解这一机制将促进有效疗法的发展 除了在重症监护室的支持性护理，这已经是非常重要的，因为许多 这些患者需要透析相关的治疗。我们的团队率先开发了“人类肾脏- 芯片上的微生理系统（MPS）概括了肾脏生理学的关键方面， 损伤的机制和反应，并测试修复机制。我们会把现有的总计划调配至 了解COVID-19介导的肾损伤的细胞和分子机制，并测试治疗 预防SARS-CoV-2引起的肾损伤和肾衰竭的策略。

PROJECT SUMMARY / ABSTRACT The ongoing coronavirus 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), and has led to over one million reported cases, significant morbidity and mortality, and extensive economic and societal disruption. The development of the disease has shown to lead to complications kidney failure. It is becoming clear that multiple mechanisms of kidney involvement in COVID- 19 infection are operative. Between 30 and 40% of severely infected COVID-19 patients develop Acute Kidney Injury with a high proportion requiring dialysis therapy in the Intensive care Unit. Moreover, evidence from biopsy and autopsy studies is emerging that kidney podocytes, proximal tubular epithelial cells and endothelial cells may become infected with SARS‑CoV‑2. Emerging data demonstrate that COVID-19 podocyte injury leads to nephrotic syndrome, proximal tubular involvement leads to acute kidney injury, and endothelial involvement leads to thrombotic microangiopathy – thus COVID-19 kidney involvement can have protean clinical manifestations, analogous to the effects of HIV infection on the kidney. No specific treatment is currently validated for COVID-19 related kidney disease, and understanding the cell-specific molecular processes associated with COVID-19 in patients with kidney disease and diabetes can have a significant impact on public health. A better understanding of the mechanism will foster development of effective therapies beyond the supportive care in the intensive critical care unit, which is already critically important as many of these patients require dialysis-related therapy. Our group has pioneered the development of `human kidney- on-a-chip' microphysiological systems (MPS), which recapitulate critical aspects of kidney physiology, assess the mechanisms and response to injury, and test reparative mechanisms. We will deploy our existing MPS to understand the cellular and molecular mechanisms of COVID-19 mediated kidney injury, and test therapeutic strategies to prevent kidney injury and kidney failure due to SARS‑CoV‑2.