Publications

Journal Article Epublish

PubMed: 40821834 DOI: 10.3389/fimmu.2025.1623309

Treatment with intravenous immunoglobulin modulates coagulation- and complement-related pathways in COVID-19 patients.

Front Immunol 16:1623309

Authors: Dominic McGrosso, Jessica Raygoza, Avnee J Kumar, Michael T Y Lam, Laura A Barnes, Sophia Karandashova, Alexia Perryman, Matthew Geriak, Mazen F Odish, Nicole G Coufal, Brian Lichtenstein, George Sakoulas, Angela Meier, Victor Nizet, Jorge A Masso-Silva

Affiliations

  • 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.
  • 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.
  • Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.
  • Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Physiology, University of California, San Diego, La Jolla, CA, United States.
  • Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States. Department of Medicine, Division of Pulmonary, Critical Care, Sleep and Physiology, University of California, San Diego, La Jolla, CA, United States.
  • Division of Respiratory Medicine, Department of Pediatrics, University of California San Diego, La Jolla, CA, United States.
  • Sharp Center for Research, San Diego, CA, United States.
  • Sanford Consortium for Regenerative Medicine, La Jolla, CA, United States.
  • Department of Pediatrics, University of California San Diego, La Jolla, CA, United States.
  • Rady Children's Hospital, San Diego, CA, United States.
  • Division of Hospital Medicine, Department of Internal Medicine, Sharp Rees Stealy Medical Group, San Diego, CA, United States.
  • Collaborative to Halt Antimicrobial Resistant Microbes (CHARM), Department of Pediatrics, University of California School of Medicine, La Jolla, CA, United States.
  • Department of Anesthesiology, Division of Critical Care, University of California, San Diego, La Jolla, CA, United States.

Abstract

Introduction

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.

Methods

We describe the first proteomic analysis from the plasma of COVID-19 patients treated with IVIG, as well as clinical outcomes.

Results

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.

Discussion

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.

MeSH

Immunoglobulins, Covid-19, Complement System Proteins, Therapeutics, Immunoglobulins, Intravenous