Covid-19 induced worsening of glomerular diseases

摘要/摘要(最多30行)： SARS-CoV-2是一种与广泛的细胞因子风暴相关的呼吸道感染。焦点和节段性 肾小球硬化和糖尿病肾病是新冠肺炎的既定危险因素 并发症。虽然这两种疾病在细胞因子风暴条件下都会恶化，但COVID的影响- 19相关细胞因子风暴对FSGS和糖尿病肾病发病过程的影响尚不清楚。我们需要FSGS和DN 新冠肺炎感染后病情加重。基于人类观察数据，我们产生了多种细胞因子 模拟新冠肺炎细胞因子风暴的鸡尾酒，并表明它们在注射时会引起多系统损伤 高剂量对啮齿动物(患者为重度新冠肺炎)的影响，并在低剂量(轻度新冠肺炎)时加重肾脏损害 病人)。研究新冠肺炎细胞因子风暴在肾小球疾病动物模型中的作用将允许 更好地了解新冠肺炎对现有疾病患者的影响。此外，中和 细胞因子风暴可能会改善住院的新冠肺炎患者的预后并防止病情恶化 受体阻断和细胞因子耗竭联合应用对肾功能的影响 在具体目标1中，申请人将研究肾小球疾病恶化和慢性肾脏疾病 新冠肺炎样细胞因子风暴诱导后的FSGS和DN。 在具体目标2中，申请人将评估过敏途径细胞因子IL-4和IL-13的影响，以及 新冠肺炎呼吸道感染时炎症途径细胞因子肿瘤坏死因子-α和趋化因子CXCL5的释放 关于先前存在的肾小球疾病。 在具体目标3中，申请人将治疗与新冠肺炎相关的肾小球疾病恶化和慢性肾脏疾病 通过耗尽或阻断细胞因子风暴而导致的FSGS和糖尿病肾病。

Summary / Abstract (max 30 lines): SARS-CoV-2 is a respiratory tract infection associated with an extensive cytokine storm. Focal and segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) are established risk factors for COVID-19 complications. Whereas both diseases can be exacerbated under cytokine storm conditions, the effect of COVID- 19 associated cytokine storm on the course of established FSGS and DN is not clear. We expect FSGS and DN to be worsened after COVID-19 infection. Based on human observational data, we generated multiple cytokine cocktails to mimic the COVID-19 cytokine storm, and showed that they cause multisystem injury when injected in rodents at high dose (severe COVID-19 in patients), and worsen kidney injury at low dose (mild COVID-19 in patients). Studying the effect of COVID-19 cytokine storm in animal models of glomerular disease will allow a better understanding of the impact of COVID-19 on patient with existing disorders. Furthermore, neutralizing the cytokine storm could potentially improve the outcome of hospitalized COVID-19 patients and prevent worsening of kidney function by using a combination of receptor blockage and cytokine depletion In Specific Aim 1, the applicant will study worsening of glomerular disease and chronic kidney disease due to FSGS and DN after induction of COVID-19 like cytokine storm. In Specific Aim 2, the applicant will assess the impact of allergy pathway cytokines IL-4 and IL-13, and inflammatory pathway cytokine TNF-α, and chemokine CXCL5 released during COVID-19 respiratory infection on pre-existing glomerular diseases. In Specific Aim 3, the applicant will treat COVID-19 related worsening of glomerular disease and chronic kidney disease FSGS and DN by depletion or blockage of the cytokine storm.