McGrosso Dominic, Raygoza Jessica, Kumar Avnee J, Lam Michael T Y, Barnes Laura A, Karandashova Sophia, Perryman Alexia, Geriak Matthew, Odish Mazen F, Coufal Nicole G, Lichtenstein Brian, Sakoulas George, Meier Angela, Nizet Victor, Masso-Silva Jorge A
Department of Pharmacology, University of California, San Diego, La Jolla, CA, United States.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, United States.
Front Immunol. 2025 Jul 31;16:1623309. doi: 10.3389/fimmu.2025.1623309. eCollection 2025.
Intravenous immunoglobulin (IVIG) is a therapy that uses pooled immunoglobulins from thousands of different donors. While it is primarily used to treat immunodeficiency and autoimmune diseases due to its immunomodulatory properties, IVIG has also been used as an off-label therapy for respiratory infections, including COVID-19. Clinical data regarding the efficacy of IVIG for COVID-19 has been controversial, and although some smaller studies have shown beneficial effects, others including a large randomized trial found no significant clinical impact but noted detrimental secondary effects.
We describe the first proteomic analysis from the plasma of COVID-19 patients treated with IVIG, as well as clinical outcomes.
Patients that received IVIG early upon hospitalization have faster clinical improvement. Proteomic analysis showed that serum from patients with COVID-19 has increased levels of proteins associated with inflammatory responses, activation of coagulation and complement pathways, and dysregulation of lipid metabolism. IVIG therapy significantly impacted pathways related to coagulation. Given known crosstalk between coagulation and complement pathways, we also analyzed complement-related proteins. Overall, treatment with IVIG appeared to modulate coagulation (KNG1, ACTB, FGA, F13B, and CPB2) and complement (C1RL, C8G and CFD) related proteins.
Our data is supported by similar findings observed in disease states other than COVID-19, where IVIG can impact coagulation and complement proteins. However, early administration seems to be critical determinants to optimize responsiveness to IVIG therapy in COVID-19.
静脉注射免疫球蛋白（IVIG）是一种使用来自数千名不同供体的混合免疫球蛋白的疗法。虽然它主要因其免疫调节特性用于治疗免疫缺陷和自身免疫性疾病，但IVIG也被用作包括COVID-19在内的呼吸道感染的非标签疗法。关于IVIG对COVID-19疗效的临床数据一直存在争议，尽管一些较小的研究显示了有益效果，但其他研究，包括一项大型随机试验，未发现显著的临床影响，但指出了有害的副作用。
我们描述了对接受IVIG治疗的COVID-19患者血浆的首次蛋白质组学分析以及临床结果。
住院后早期接受IVIG治疗的患者临床改善更快。蛋白质组学分析表明，COVID-19患者血清中与炎症反应、凝血和补体途径激活以及脂质代谢失调相关的蛋白质水平升高。IVIG治疗对与凝血相关的途径有显著影响。鉴于已知凝血和补体途径之间的相互作用，我们还分析了补体相关蛋白。总体而言，IVIG治疗似乎调节了与凝血（KNG1、ACTB、FGA、F13B和CPB2）和补体（C1RL、C8G和CFD）相关的蛋白质。
我们的数据得到了在COVID-19以外的疾病状态中观察到的类似发现的支持，在这些疾病中IVIG可以影响凝血和补体蛋白。然而，早期给药似乎是优化COVID-19患者对IVIG治疗反应性的关键决定因素。
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