Effect of intravenous immunoglobulin on mortality in hospitalized patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Background and Aims: We performed a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of intravenous immunoglobulin (IVIG) on mortality outcomes among hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: We systematically searched electronic databases up to June 1, 2023. Pooled odds ratio (OR) of mortality with a 95% confidence interval (CI) was generated using a random-effects model. The risk of bias was appraised using the Cochrane risk-of-bias Version 2 tool for randomized trials. Results: Nine RCTs were included: three RCTs had an overall low risk of bias, four RCTs had some concerns in the overall risk of bias, and two RCTs trials had an overall high risk of bias. The use of IVIG indicated a significant reduction in the odds of mortality (pooled OR = 0.69; 95% CI 0.50-0.96) relative to nonuse of IVIG. Subgroup analysis in patients with a severe course of COVID-19 revealed no significant reduction in the odds of mortality (pooled OR = 0.58; 95% CI 0.29-1.16). Conclusions: We suggest exercising caution when interpreting effectiveness of IVIG in reducing mortality among hospitalized patients with COVID-19. Our findings emphasize for larger trials with rigorous study designs to better understand the impact of IVIG, particularly in those with severe COVID-19.