In COVID-19, acute respiratory distress syndrome (ARDS) and thrombotic events are frequent, life-threatening complications. Autopsies commonly show arterial thrombosis and severe endothelial damage. Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. Mannan-binding lectin-associated serine protease-2 (MASP-2), the lectin pathway’s effector enzyme, binds the nucleocapsid protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), resulting in complement activation and lung injury. Narsoplimab, a fully human immunoglobulin gamma 4 (IgG4) monoclonal antibody against MASP-2, inhibits lectin pathway activation and has anticoagulant effects. In this study, the first time a lectin-pathway inhibitor was used to treat COVID-19, six COVID-19 patients with ARDS requiring continuous positive airway pressure (CPAP) or intubation received narsoplimab under compassionate use. At baseline and during treatment, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed. Narsoplimab treatment was associated with rapid and sustained reduction of CEC and concurrent reduction of serum IL-6, IL-8, CRP and LDH. Narsoplimab was well tolerated; no adverse drug reactions were reported. Two control groups were used for retrospective comparison, both showing significantly higher mortality than the narsoplimab-treated group. All narsoplimab-treated patients recovered and survived. Narsoplimab may be an effective treatment for COVID-19 by reducing COVID-19-related endothelial cell damage and the resultant inflammation and thrombotic risk.

在 COVID-19 中，急性呼吸窘迫综合征 (ARDS) 和血栓事件是常见的危及生命的并发症。尸检通常显示动脉血栓形成和严重的内皮损伤。内皮损伤可激活补体凝集素途径，在 ARDS 和血栓形成中发挥早期和核心致病作用。甘露聚糖结合凝集素相关丝氨酸蛋白酶 2 (MASP-2) 是凝集素途径的效应酶，与严重急性呼吸综合征相关冠状病毒 2 (SARS-CoV-2) 的核衣壳蛋白结合，导致补体激活和肺损伤受伤。 Narsoplimab 是一种针对 MASP-2 的全人免疫球蛋白 γ 4 (IgG4) 单克隆抗体，可抑制凝集素途径激活并具有抗凝血作用。在这项研究中，首次使用凝集素途径抑制剂治疗 COVID-19，六名需要持续气道正压通气 (CPAP) 或插管的 ARDS 的 COVID-19 患者在同情使用下接受了 narsoplimab 治疗。在基线和治疗期间，评估了循环内皮细胞 (CEC) 计数以及白细胞介素 6 (IL-6)、白细胞介素 8 (IL-8)、C 反应蛋白 (CRP) 和乳酸脱氢酶 (LDH) 的血清水平。 Narsoplimab 治疗与 CEC 的快速持续降低以及血清 IL-6、IL-8、CRP 和 LDH 的同时降低相关。 Narsoplimab 的耐受性良好；未报告药物不良反应。使用两个对照组进行回顾性比较，均显示出比 narsoplimab 治疗组显着更高的死亡率。所有接受 narsoplimab 治疗的患者均康复并存活。 Narsoplimab 可能是一种有效治疗 COVID-19 的方法，可减少与 COVID-19 相关的内皮细胞损伤以及由此产生的炎症和血栓形成风险。