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Clinical Trial
. 2021 Feb 19:12:627844.
doi: 10.3389/fimmu.2021.627844. eCollection 2021.

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

Wei Cao  1 , Xiaosheng Liu  1   2   3 , Ke Hong  4 , Zhiyong Ma  5 , Yuelun Zhang  6 , Ling Lin  1 , Yang Han  1 , Yong Xiong  5 , Zhengyin Liu  1 , Lianguo Ruan  4 , Taisheng Li  1   2   3
Affiliations
Clinical Trial

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

Wei Cao et al. Front Immunol. .

Erratum in

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Selection and analysis process of the high-dose intravenous immunoglobulin (IVIg) and control groups.
Figure 2
Figure 2
Dynamic of cytokines and inflammatory markers in severe hospitalized coronavirus disease 2019 (COVID-19) patients with high-dose intravenous immunoglobulin (IVIg) therapy and/or standard care.
Figure 3
Figure 3
Subgroup and multivariable analyses of the impact of intravenous immunoglobulin (IVIg) therapy on 28-day mortality after inverse probability of treatment weighting (IPTW) adjusted. Demographic-adjusted: controlled for age and sex as covariates; fully adjusted: controlled for age, sex, comorbidity, disease onset days, baseline seven scale category, the use of arbidol, LPV/r, IFN, RBV, OSV, antibiotics, antifungals, TCM, glucocorticoids, LMWH as covariates.
Figure 4
Figure 4
Kaplan-Meier curves for overall survival in severe hospitalized coronavirus disease 2019 (COVID-19) patients with high-dose intravenous immunoglobulin (IVIg) therapy and/or standard care.
See this image and copyright information in PMC

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