Immune Tolerance Network

项目摘要/摘要：抗CD14(CATT) SARS-CoV-2大流行继续在世界各地传播，导致大范围疾病 严重的死亡率，使医疗保健系统不堪重负，扰乱全球 经济舱。严重的疾病是由宿主细胞的病毒感染导致产生 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 通过钝化宿主的先天免疫炎症来增加抗病毒治疗的治疗 使用IC14对病毒感染的宿主细胞的反应，IC14是一种特异性的封闭性单抗 巨噬细胞、树突状细胞等天然细胞上的CD14模式识别受体 免疫系统。结合主要的抗病毒药物(如瑞美西韦)，这种治疗方法 策略应减少宿主的炎症反应，加快疾病的解决。这个 主要假设是抑制CD14模式识别受体会减少 有害宿主对SARS-CoV-2病毒和继发性炎症反应的强度 新冠肺炎患者的组织损伤和改善预后。我们将进行一项 在美国15个临床中心300名患者中进行的多中心随机对照试验 IC14在因呼吸道疾病住院患者中的有效性和安全性 SARS-CoV-2。在目标1中，我们将确定IC14是否缩短了解决问题的时间 使用八点序数标度的疾病。在目标2中，我们将确定IC14是否减少 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 IC14是否减轻全身炎症的严重程度和鼻腔内病毒的恢复 棉签。总体而言，这一计划将决定IC14治疗是否是一种有效的新方法 减轻SARS-CoV-2病毒引发的全身炎症和器官损伤的方法 并改善新冠肺炎患者的住院治疗结果。

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.