Effects of Intravenous Immunoglobulin on the Course of Severe COVID-19: Results From a Retrospective Data Analysis of a Patient Cohort in Turkey Treated With or Without Octagam®

Abstract

Background: There is some evidence from case reports and a few studies in China that critically ill COVID-19 patients may benefit from treatment with intravenous immunoglobulins (IVIG). We compared clinical outcomes and biomarkers in a Turkish cohort of patients with severe COVID-19 who were treated with the institution's standard of care (SOC), either alone or in combination with IVIG.Methods: Data from COVID-19 patients treated in two intensive care units at the University hospital of Istanbul was analyzed retrospectively. Patients received preliminary SOC according to the institution's treatment algorithm, to which Octagam 5% at 30 g/day for 5 days was added in one of the two wards. Both groups were compared regarding baseline characteristics, survival, and changes in inflammation markers (C-reactive protein=CRP, ferritin, procalcitonin, interleukin-6, D‑dimer, leukocytes). Imbalance in baseline APACHE II scores was addressed by propensity-score-matching; otherwise Kaplan-Meier and multiple logistic regression models were used.Results: Data from 93 patients was analyzed, 51 had received IVIG and 42 had not. About 75% of patients were male and both groups had comparable body mass index (BMI) and blood group distribution. IVIG-treated patients were younger (means 65 vs. 71 years) and had slightly lower baseline disease scores (APACHE II: 20.6 vs. 22.4; SOFA: 5.0 vs. 7.0). Overall survival (OS) was 61% in the IVIG and 38% in the control group. After controlling for imbalances at baseline, there was still a trend for better OS (OR: 2.2, 95%CI: 0.9-5.4, p=0.091) and a significantly longer median survival time with IVIG (68 vs. 18 days, p=0.014). IVIG significantly reduced CRP levels, but had no relevant effect on other inflammation markers.Conclusion: Adjunct treatment with IVIG might add to the COVID-19 armamentarium, but results need to be confirmed in a randomized, controlled trial.

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial

“…**Only in survivors at day 90. consistent with the main result and did not show any beneficial effect of IVIG (figure 3; appendix 1 p 18). A posthoc analysis of mortality showed no statistically significant interaction between the IVIG and corti costeroid administration or body-mass index for the unadjusted mortality odds ratios at day 28 and day 90 (appendix 1 pp 18,[31][32]. The sensitivity analysis done on the per-protocol population for both the primary outcome and competing events confirmed the non-significant treatment effect shown by the intention-to-treat analysis (appendix 1 p 19).…”

“…14 Retrospective observational studies have suggested that IVIG decrease mortality and duration of invasive mechanical ventilation in COVID-19-associated ARDS. [15][16][17][18][19] Further more, it has been reported in China that about a third of patients with COVID-19 and ARDS have been treated with IVIG, without the specific effect of IVIG being evaluated. [20][21][22] However, because of the cost and scarcity of IVIGs, which is currently indicated in various autoimmune and inflammatory diseases, showing the efficacy and safety of IVIG in patients who are critically ill with COVID-19 is needed to explore IVIG therapy as a viable treatment option.…”