Intravenous Immunoglobulin Therapy for Critically Ill COVID-19 Patients With Different Inflammatory Phenotypes: A Multicenter, Retrospective Study

Abstract

BackgroundThe benefits of intravenous immunoglobulin administration are controversial for critically ill COVID-19 patients.MethodsWe analyzed retrospectively the effects of immunoglobulin administration for critically ill COVID-19 patients. The primary outcome was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. Cluster analysis was used to perform phenotype analysis.ResultsBetween January 1 and February 29, 2020, 754 patients with complete data from 19 hospitals were enrolled. Death at 28 days occurred for 408 (54.1%) patients. There were 392 (52.0%) patients who received intravenous immunoglobulin, at 11 (interquartile range (IQR) 8, 16) days after illness onset; 30% of these patients received intravenous immunoglobulin prior to intensive care unit (ICU) admission. By unadjusted analysis, no difference was observed for 28-day mortality between the immunoglobulin and non-immunoglobulin groups. Similar results were found by propensity score matching (n = 506) and by IPTW analysis (n = 731). Also, IPTW analysis did not reveal any significant difference between hyperinflammation and hypoinflammation phenotypes.ConclusionNo significant association was observed for use of intravenous immunoglobulin and decreased mortality of severe COVID-19 patients. Phenotype analysis did not show any survival benefit for patients who received immunoglobulin therapy.

Benefits of high-dose intravenous immunoglobulin on mortality in patients with severe COVID-19: An updated systematic review and meta-analysis

“…Results showed that IVIg did not reduce the mortality in different groups (Critically ill type: RR= 1.16 [0.71, 1.91], P = 0.56, I 2 = 80%; Severe type: RR= 0.65 [0.33, 1.26], P = 0.20, I 2 = 71%; Non-severe type: RR= 1.52 [0.10, 24.35], P = 0.77, I 2 = 30%; P for interaction= 0.363) ( Figure 2B ). We also conducted subgroup analysis based on the differentially reported adjusted RR from four cohort studies ( 44 , 45 , 47 , 49 ), with similar results ( Figure S1B ).…”

“…2B). We also conducted subgroup analysis based on the differentially reported adjusted RR from four cohort studies (44,45,47,49), with similar results (Figure S1B). Effects of IVIg on the length of hospital stay were reported in 11 studies, including five RCT studies (18,19,22,41,42) 2).…”

“…Overall, the application of IVIg did not reduce the mortality in RCT studies (RR= 0.57 [0.19, 1.68], P = 0.30; I 2 = 72%), or cohort studies (RR= 0.93, [0.63, 1.36], P = 0.71; I 2 = 78%) ( Figure 2A ). As there were five cohort studies that reported more than one adjusted effect estimated with different statistical methods ( 20 , 44 , 45 , 47 , 49 ), we additionally calculated the pooled RR of cohort studies as sensitive analysis (adjusted RR= 0.91, [0.67, 1.26], P = 0.58; I 2 = 81%) ( Figure S1A ). These data suggested no significant improvement of IVIg on mortality of overall COVID-19 patients, and the certainty level was low due to the inconsistency in design bias and outcome measurement of studies.…”

“…Four studies were considered with a low risk of bias (43)(44)(45)47), and the others were considered with the high risk of bias. The further ROBINS-I analysis showed that three studies were judged to be at moderate risk of overall bias (44,48,49), while the rest were considered with a serious risk of bias (Tables S5, S6). The funnel plots and results from Egger's regression test showed that no significant publication bias was observed (intercept= 0.90 [-2.68, 0.88], P= 0.30) (Figure S9).…”

IgG response to spike protein of SARS-CoV-2 in healthy individuals and potential of intravenous IgG as treatment for COVID-19

“…Another study found that COVID-19 patients who received IVIg had reduced mortality relative to controls (20% vs. 48.5%) [9]. However, there still several new studies reporting that IVIg didn't increase the benefits of severe COVID-19 patients or moderate-to-severe acute respiratory distress syndrome (ARDS) patients [26,27]. Hence, whether the IVIg is effective for treating COVID-19 patients or not needs more clinical data.…”