The complement system is a stakeholder of the innate and adaptive immune system and has evolved as a crucial player of defense with multifaceted biological effects. Activation of three complement pathways leads to consecutive enzyme reactions resulting in complement components (C3 and C5), activation of mast cells and neutrophils by anaphylatoxins (C3a and C5a), the formation of membrane attack complex (MAC) and end up with opsonization. However, the dysregulation of complement cascade leads to unsolicited cytokine storm, inflammation, deterioration of alveolar lining cells, culminating in acquired respiratory destructive syndrome (ARDS). Similar pathogenesis is observed with the middle east respiratory syndrome (MERS), severe acquired respiratory syndrome (SARS), and SARS-CoV-2. Activation of the lectin pathway via mannose-binding lectin associated serine protease 2 (MASP2) is witnessed under discrete viral infections including COVID-19. Consequently, the spontaneous activation and deposits of complement components were traced in animal models and autopsy of COVID-19 patients. Pre-clinical and clinical studies evidence that the inhibition of complement components results in reduced complement deposits on target and non-target tissues, and aid in recovery from the pathological conditions of ARDS. Complement inhibitors (monoclonal antibody, protein, peptide, small molecules, etc.) exhibit great promise in blocking the activity of complement components and its downstream effects under various pathological conditions including SARS-CoV. Therefore, we hypothesize that targeting the potential complement inhibitors and complement cascade to counteract lung inflammation would be a better strategy to treat COVID-19.

补体系统是先天性和适应性免疫系统的利益相关者，并已发展成为具有多方面生物效应的防御的关键参与者。三个补体途径的激活导致连续的酶反应，产生补体成分（C3 和 C5），过敏毒素（C3a 和 C5a）激活肥大细胞和中性粒细胞，形成膜攻击复合物（MAC）并最终调理作用。然而，补体级联的失调会导致自发的细胞因子风暴、炎症、肺泡衬里细胞恶化，最终导致获得性呼吸破坏综合征（ARDS）。中东呼吸综合征 (MERS)、严重获得性呼吸综合征 (SARS) 和 SARS-CoV-2 也观察到类似的发病机制。在包括 COVID-19 在内的离散病毒感染下，可以观察到通过甘露糖结合凝集素相关丝氨酸蛋白酶 2 (MASP2) 激活凝集素途径。因此，在动物模型和 COVID-19 患者尸检中追踪了补体成分的自发激活和沉积。临床前和临床研究证明，补体成分的抑制会导致靶组织和非靶组织上的补体沉积减少，并有助于 ARDS 病理状况的恢复。补体抑制剂（单克隆抗体、蛋白质、肽、小分子等）在阻断包括 SARS-CoV 在内的各种病理条件下补体成分的活性及其下游效应方面表现出巨大的前景。因此，我们假设针对潜在的补体抑制剂和补体级联反应来对抗肺部炎症将是治疗 COVID-19 的更好策略。