High-Dose Intravenous Immunoglobulin in Severe Coronavirus Disease 2019: A Multicenter Retrospective Study in China

Front Immunol. 2021 Feb 19:12:627844. doi: 10.3389/fimmu.2021.627844. eCollection 2021.

Abstract

Background: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking.

Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis.

Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg.

Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.

Keywords: 28-day mortality; COVID-19; high-dose intravenous immunoglobulin; immunomodulation; inflammatory markers.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • COVID-19 / blood
  • COVID-19 / mortality*
  • COVID-19 Drug Treatment*
  • China / epidemiology
  • Disease-Free Survival
  • Female
  • Ferritins / blood
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage*
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Retrospective Studies
  • SARS-CoV-2 / metabolism*
  • Survival Rate

Substances

  • IL10 protein, human
  • IL6 protein, human
  • Immunoglobulins, Intravenous
  • Interleukin-6
  • Interleukin-10
  • Ferritins