Efficacy of High-Dose Polyclonal Intravenous Immunoglobulin in COVID-19: A Systematic Review

Background: Although several therapeutic strategies have been investigated, the optimal treatment approach for patients with coronavirus disease (COVID-19) remains to be elucidated. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of polyclonal intravenous immunoglobulin (IVIG) therapy in COVID-19. Methods: A systematic literature search using appropriate medical subject heading (MeSH) terms was performed through Medline (PubMed), EMBASE, SCOPUS, OVID and Cochrane Library electronic databases. The main outcomes considered were mortality and safety of IVIG versus placebo/standard of care. This review was carried out in accordance with Cochrane methodology including the risk bias assessment and grading of the quality of evidence. Measures of treatment effect were mean differences (MD) together with 95% confidence intervals (CIs) for continuous outcome measures and risk ratio (RR) or MD for binary outcomes. Two reviewers independently extracted data from individual studies, and disagreements were resolved by a third reviewer. Results: A total of 2401 COVID-19 patients from 10 studies (four randomized controlled trials (RCT) and six non-randomized controlled trials (non-RCTs)) were included in the analysis. Participants received IVIG or placebo/standard of care. The use of IVIG was not associated with a significantly reduced risk of death (RR 0.50, 95% CIs 0.18-1.36, p = 0.17 for RCTs; RR 0.95, 95% CIs 0.61-1.58, p = 0.94 for non-RCTs; low certainty of evidence). IVIG significantly reduced the length of hospital stay (MD -2.24, 95% CIs -3.20/-1.27; p = 0.00001; low certainty of evidence), although this difference was significant only for studies evaluating moderate COVID-19 patients. No significant difference was observed in the incidence of overall and serious adverse events between IVIG recipients and controls (very low certainty of evidence). Conclusions: The current evidence from the literature does not support the use of IVIG in COVID-19 patients.