Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic 1 . The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes 1 . Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a–C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a–C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19. Blockade of the C5a–C5aR1 axis using anti-C5aR1 monoclonal antibodies prevented inflammation associated with COVID-19.

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COVID-19 炎症与 C5a-C5aR1 轴激活的关联

2019 年冠状病毒病 (COVID-19) 是一种由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染引起的疾病，并已导致大流行 1 。C5a 补体因子及其受体 C5aR1（也称为 CD88）通过募集和激活中性粒细胞和单核细胞，在多种炎症反应的启动和维持中发挥关键作用 1 。在这里，我们提供了免疫反应的纵向分析，包括免疫细胞的表型分析以及对 COVID-19 严重程度不同阶段患者（包括无症状或有症状的患者）血液和支气管肺泡灌洗液中存在的可溶性因子的评估。肺炎或急性呼吸窘迫综合征。可溶性 C5a 的水平与 COVID-19 的严重程度成比例增加，并且在血液和肺髓细胞中发现了 C5aR1 受体的高表达水平，这支持了 C5a-C5aR1 轴在急性呼吸窘迫综合征的病理生理学中的作用。抗 C5aR1 治疗性单克隆抗体可阻止 C5a 介导的人骨髓细胞的募集和激活，并抑制人 C5aR1 敲入小鼠的急性肺损伤。这些结果表明，阻断 C5a-C5aR1 轴可用于限制受损器官中骨髓细胞的浸润，并防止与 COVID-19 患者急性呼吸窘迫综合征相关的过度肺部炎症和内皮炎。使用抗 C5aR1 单克隆抗体阻断 C5a-C5aR1 轴可预防与 COVID-19 相关的炎症。