COVID-19 is a clinical syndrome ranging from mild symptoms to severe pneumonia that often leads to respiratory failure, need for mechanical ventilation, and death. Most of the lung damage is driven by a surge in inflammatory cytokines [interleukin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM-CSF)]. Blunting this hyperinflammation with immunomodulation may lead to clinical improvement. GM-CSF is produced by many cells, including macrophages and T-cells. GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs). In animal models of respiratory infections, the intranasal administration of GM-CSF increased the proliferation of AMs and improved outcomes. Increased levels of GM-CSF have been recently described in patients with COVID-19 compared to healthy controls. While GM-CSF might be beneficial in some circumstances as an appropriate response, in this case the inflammatory response is maladaptive by virtue of being later and disproportionate. The inhibition of GM-CSF signaling may be beneficial in improving the hyperinflammation-related lung damage in the most severe cases of COVID-19. This blockade can be achieved through antagonism of the GM-CSF receptor or the direct binding of circulating GM-CSF. Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Prospective, randomized, placebo-controlled trials are ongoing. Anti-GM-CSF monoclonal antibodies, TJ003234 and gimsilumab, will be tested in clinical trials in patients with COVID-19, while lenzilumab received FDA approval for compassionate use. These trials will help inform whether blunting the inflammatory signaling provided by the GM-CSF axis in COVID-19 is beneficial.

COVID-19是一种临床综合征，范围从轻度症状到严重的肺炎，通常会导致呼吸衰竭，需要机械通气并导致死亡。大多数肺损伤是由炎性细胞因子[白介素-6，干扰素-γ和粒细胞-单核细胞刺激因子（GM-CSF）]激增驱动的。通过免疫调节抑制这种过度炎症可能会导致临床改善。GM-CSF由许多细胞产生，包括巨噬细胞和T细胞。GM-CSF衍生信号参与巨噬细胞（包括肺泡巨噬细胞（AM））的分化。在呼吸道感染的动物模型中，鼻内施用GM-CSF可增加AM的增殖并改善结局。与健康对照组相比，最近在COVID-19患者中发现了GM-CSF水平升高。尽管在某些情况下，GM-CSF作为适当的反应可能是有益的，但在这种情况下，炎症反应由于迟发和不成比例而具有不良适应性。在最严重的COVID-19病例中，抑制GM-CSF信号传导可能有助于改善与过度炎症相关的肺部损伤。可以通过拮抗GM-CSF受体或直接结合循环的GM-CSF来实现这种阻断。用单次静脉注射剂量马夫利单抗（一种结合GM-CSF受体α的单克隆抗体）治疗的COVID-19患者的初步发现显示氧合改善，住院时间缩短。前瞻性，随机，安慰剂对照试验正在进行中。抗GM-CSF单克隆抗体TJ003234和gimsilumab将在COVID-19，而lenzilumab则因同情使用而获得FDA批准。这些试验将有助于揭示使COVID-19中的GM-CSF轴提供的炎症信号减弱是否有益。