The outcome of using intravenous immunoglobulin (IVIG) in critically ill COVID-19 patients’: a retrospective, multi-centric cohort study

Abstract

Background During the COVID-19 pandemic, different treatments have been used in critically ill patients. Using intravenous immunoglobulin (IVIG) has been suggested in various studies as an effective option. Our study aims to access the efficacy of IVIG in critically ill COVID-19 patients. Methods In this retrospective matched cohort study, records of three tertiary centers with a large number of COVID-19 admissions were evaluated and used. Based on treatment options, patients were divided into two groups, standard COVID-19 treatment (109 patients) and IVIG treatment (74 patients) patients. Also, the effect of IVIG in different dosages was evaluated. Patients with IVIG treatment were divided into three groups of low (0.25 gr/kg), medium (0.5 gr/kg), and high (1 gr/kg) dose. Data analysis was performed using an independent t test and one-way analysis of variance (ANOVA) to compare the outcomes between two groups, including duration of hospitalization, intensive care unit (ICU) length of stay, and mortality rate. Results The duration of hospitalization in the IVIG group was significantly longer than standard treatment (13.74 days vs. 11.10 days, p < 0.05). There was no significant difference between the two groups in ICU length of stay, the number of intubated patients, and duration of mechanical ventilation (p > 0.05). Also, initial outcomes in IVIG subgroups were compared separately with the standard treatment group. The results indicated that only the duration of hospitalization in the IVIG subgroup with medium dose is significantly longer than the standard treatment group (p < 0.01). Conclusion Our data indicate that the use of IVIG in critically ill COVID-19 patients could not be beneficial, based on no remarkable differences in duration of hospitalization, ICU length of stay, duration of mechanical ventilation, and even mortality rate.

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

“…After screening, 17 studies (including five RCT ( 18 , 19 , 22 , 41 , 42 ) and 12 cohort studies ( 20 , 21 , 43 – 52 ) that were considered to meet the selection criteria and included in the meta-analysis. Different form the latest study ( 28 ), four studies were newly identified and included in this meta-analysis ( 48 – 50 , 52 ).…”

“…Effects of IVIg on the need for mechanical ventilation were reported in eight studies, including three RCT studies ( 19 , 41 , 42 ) (RR= 0.77 [0.49, 1.21], P = 0.26; I 2 = 39%) and five cohort studies ( 21 , 44 , 46 , 48 , 50 ) (RR= 1.02 [0.76, 1.37], P = 0.89; I 2 = 66%) ( Figure S3 ). One RCT study was excluded in this analysis because all patients had applied mechanical ventilation before allocating to receive IVIg treatment ( 22 ).…”

“…Results from other studies also suggested the early administration of IVIg in treating patients with COVID-19 ( 44 , 50 , 53 , 54 ) or patients with septic shock ( 55 ). For COVID-19 patients who already progressed to critically ill status, the high-dose IVIg was ineffective, indicating its short therapeutic window ( 48 ). The major challenge in the application of high-dose IVIg or other immunomodulators is to grasp the proper therapeutic window of the hyper-inflammatory stage of SARS-CoV-2 infection ( 5 , 56 – 58 ).…”

“…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).…”

Evaluation of the Efficacy and Safety of Intravenous Immunoglobulin (IVIG) in Moderate-to-Severe Hospitalized COVID-19 Patients: A Randomized, Open-Label Parallel-Group Study

“…On the other hand, a retrospective, multicenter cohort study assessing the outcome of IVIG in critically ill COVID-19 patients found no remarkable differences in hospitalization, ICU length of stay, duration of mechanical ventilation, and even mortality rate [ 40 ]. A multicenter, double-blinded, placebo-controlled, and phase 3 trial involving moderate-to-severe COVID-19 ARDS showed that IVIG did not improve clinical outcomes at Day 28 and showed an insignificant increase in adverse events [ 41 ].…”