Intravenous immunoglobulin therapy in viral infections: Lessons learned from COVID-19

OBJECTIVES: Intravenous immunoglobulin (IVIg) exerts both antiviral and immunomodulatory effects, but its role in viral infections remains incompletely defined. This review aims to provide an integrated overview of IVIg mechanisms of action and to evaluate its clinical relevance in viral diseases, with particular emphasis on coronavirus disease 2019 (COVID-19). METHODS: A structured narrative literature review was conducted using PubMed (MEDLINE) and complemented by manual screening of the reference lists of relevant publications. The search included studies available through early 2026 addressing the mechanisms of action of IVIg and its clinical application in viral infections. Records were screened by title, abstract, and full-text evaluation according to predefined eligibility criteria, and the evidence was synthesized qualitatively. RESULTS: IVIg acts through multiple mechanisms, including fragment antigen binding (Fab)-mediated neutralization, fragment crystallizable (Fc) receptor modulation, complement inhibition, cytokine regulation, and neonatal Fc receptor (FcRn)-mediated immunoglobulin G clearance. In immunodeficient patients, IVIg provides passive antiviral immunity and improves viral control. In contrast, in severe viral infections such as COVID-19, disease severity is largely driven by immune dysregulation. In this context, IVIg may exert benefit primarily through immunomodulatory effects rather than direct antiviral activity. Clinical studies in COVID-19 have shown heterogeneous results, influenced by treatment timing, patient selection, dosing strategies, and concomitant therapies. CONCLUSIONS: IVIg should be considered a context-dependent immunomodulatory therapy rather than a universal antiviral strategy. Its clinical efficacy likely depends on alignment between its mechanisms and disease-specific immunopathology, highlighting the need for biomarker-guided and stage-specific therapeutic approaches.