Intravenous Immunoglobulin Gamma for Severe Cases of Coronavirus Disease of 2019: A Randomized Placebo-Controlled Double-Blinded Clinical Trial

Abstract Background: Coronavirus disease of 2019 (COVID-19) with high-transmission power has infected people in many countries around the world. Discovering an effective medication for the treatment of this disease, especially in severe cases, has become the subject of intense scientific investigations. Therefore, the objective of this study was to evaluate the efficacy of intravenous immunoglobulin (IVIg) in patients with severe COVID-19 infection.Methods: The study was conducted as a randomized placebo-controlled double-blinded clinical trial. Fifty-nine patients with severe COVID-19 infection who did not respond to initial treatment were randomly assigned into two groups. One group received IVIg (human) four vials every day for three days in addition to initial treatment, and the other group received placebo. Patients’ demographic, clinical, and selected laboratory test results, as well as the occurrence of in-hospital mortality, were recorded. Result: Among included patients, 30 patients received IVIg and 29 patients received placebo. Demographics, clinical characteristics and evaluated laboratory tests of two groups were not statistically different (P>0.05). The in-hospital mortality rate was significantly lower in the IVIg group as compared to the control group (6 [20.0%] vs 14 [48.3%], respectively, p = 0.022). Multivariate regression analysis demonstrated that administration of IVIg had a significant impact on mortality rate (aOR= 0.003 [95%CI: 0.001 - 0.815], p=0.042).Conclusion: Our study was the first randomized double-blinded study that demonstrated that the administration of IVIg in patients with severe COVID-19 infection who did not respond to initial treatment could improve their clinical outcome and reduce the mortality rate. However, further multicenter studies with larger samples size are required to confirm the applicability of using this medication as the standard treatment.Trial registration: The study protocol is registered at the Iranian Registry of Clinical Trials (www.IRCT.ir) with the registration number of IRCT20200501047259N1. Registered 17 May 2020. Retrospectively registered.