Immune Tolerance Network

项目摘要/摘要：抗CD 14（CaTT） SARS-CoV-2大流行继续在世界各地蔓延，造成广泛的疾病 死亡率高，医疗保健系统负担过重， 经济严重的疾病是由病毒感染宿主细胞引起的， 引起严重器官损伤的继发性炎症反应。我们打算测试一部小说 通过减弱宿主先天免疫炎症反应， 使用IC 14对病毒感染的宿主细胞进行应答，IC 14是针对病毒感染的特异性阻断单克隆抗体。 巨噬细胞、树突状细胞和其他先天性巨噬细胞上的CD 14模式识别受体 免疫系统与主要抗病毒药物（如Remdesivir）联合使用， 策略应该减少宿主炎症反应并加速疾病消退。的 主要的假设是，抑制CD 14模式识别受体将减少 宿主对SARS-CoV-2病毒的有害炎症反应强度和继发性炎症反应 组织损伤和改善COVID-19疾病患者的预后。我们将进行 在美国15个临床中心的300例患者中进行的多中心随机对照试验， 确定IC 14在因呼吸系统疾病住院的患者中的疗效和安全性， SARS-CoV-2。在目标1中，我们将确定IC 14是否改善了以下分辨率的时间： 疾病使用八点顺序量表。在目标2中，我们将确定IC 14是否降低 需要高水平的呼吸支持，包括ICU护理。在目标3中，我们将确定 IC 14是否降低全身炎症的严重程度和鼻内病毒的恢复 棉签总的来说，该计划将确定IC 14治疗是否是一种有效的新疗法。 减轻SARS-CoV-2病毒引发的全身炎症和器官损伤的方法 并改善因COVID-19疾病住院的患者的预后。

Project Summary/Abstract: Anti CD14 (CaTT) The SARS-CoV-2 pandemic continues to spread around the world, causing widespread illness with significant mortality, overburdening health care systems and disrupting the global economy. Severe illness is caused by viral infection of host cells leading to the generation of secondary inflammatory responses that cause serious organ injury. We propose to test a novel treatment that will add to antiviral therapy by blunting the host innate immune inflammatory response to virally infected host cells using IC14, a specific blocking monoclonal antibody to the CD14 pattern recognition receptor on macrophages, dendritic cells and other cells of the innate immune system. In combination with a primary antiviral drug (e.g. remdesivir), this treatment strategy should reduce host inflammatory responses and speed resolution of illness. The primary hypothesis is that inhibiting the CD14 pattern recognition receptor will reduce the intensity of deleterious host inflammatory responses to the SARS-CoV-2 virus and secondary tissue damage and improve outcomes in patients with COVID-19 illness. We will conduct a multicenter randomized controlled trial in 300 patients in 15 US clinical centers in order to determine the efficacy and safety of IC14 in patients hospitalized with respiratory disease due to SARS-CoV-2. In Aim 1 we will determine whether IC14 improves the time to resolution of disease using an eight-point ordinal scale. In Aim 2 we will determine whether IC14 reduces the need for high level respiratory support, including ICU care. In Aim 3 we will determine whether IC14 reduces the severity of systemic inflammation and the recovery of virus in nasal swabs. Overall, this program will determine whether treatment with IC14 is an effective new approach to lessen systemic inflammation and organ injury triggered by the SARS-CoV-2 virus and improves outcomes in patients hospitalized with COVID-19 illness.