ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1623309
This article is part of the Research TopicAntibody-Based Therapeutics for Respiratory DiseasesView all 4 articles
Treatment With Intravenous Immunoglobulin Modulates Coagulation-and Complement-related Pathways in COVID-19 Patients
Provisionally accepted
Jorge Adrian Masso-Silva1,2*
Dominic Mcgrosso1
Jesica Raygoza1
Avnee Kumar1,2Michael Lam1,2
Laura Barnes1,2Sophia Karandashova1Alexia Perryman1,2Matthew Geriak3Mazen F Odish1
Nicole Coufal1,4,5Brian Lichtenstein6
George Sakoulas1,6
Angela Meier1
Victor Nizet1- 1University of California, San Diego, La Jolla, United States
- 2VA San Diego Health System, San Diego, United States
- 3Sharp Center for Research, San Diego, United States
- 4Sanford Consortium for Regenerative Medicine, La Jolla, United States
- 5Rady Children's Hospital, San Diego, United States
- 6Sharp Rees Stealy Medical Group, San Diego, United States
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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. Here, we describe the first proteomic analysis from the plasma of COVID-19 patients treated with IVIG. 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. However, early administration seems to be critical determinants to optimize responsiveness to IVIG therapy in COVID-19.
Keywords: SARS-CoV-2, COVID-19, ARDS, Intravenous Immunoglobulin, IVIg, Mass Spectrometry, Tandem mass tag, coagulation
Received: 05 May 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Masso-Silva, Mcgrosso, Raygoza, Kumar, Lam, Barnes, Karandashova, Perryman, Geriak, Odish, Coufal, Lichtenstein, Sakoulas, Meier and Nizet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jorge Adrian Masso-Silva, University of California, San Diego, La Jolla, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.