Efficacy of intravenous immunoglobulin for Critically Ill Patients With COVID-19: A meta and trial sequential analysis (preprint)

ABSTRACT

Background: A substantial portion of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can progress to critical illness which is associated with high mortality, and prolonged length of hospital stay. Currently, intravenous immunoglobulin (IVIG) therapy is reported widely in these specific population globally. However, the impact of IVIG treatment on clinically relevant outcomes in the critically ill patients with COVID-19 still remained controversial.Methods: The major databases including PubMed, Embase and Cochrane Central Register were searched from January 1, 2019 through January 12, 2022. Studies were limited to severely ill patients with confirmed SARS-CoV-2 infection who receiving IVIG with a comparative group. The primary outcome was the overall mortality. Length of stay (LOS) in the intensive care unit (ICU) and hospital, utilization rate of invasive mechanical ventilation (IMV) and ventilators free days were secondary outcomes. Meanwhile, sensitivity and subgroup analyses, as well as a trial sequential analysis (TSA), were performed.Results: 4 prospective randomized controlled trials (RCT) and 6 retrospective cohort studies (involving 2,054 participants) met the inclusion criteria and were included in our meta-analysis. Compare to standard of care (SOC), the use of IVIG was not associated with decreased odds of death significantly (OR 1.03; 95% CI 0.63–1.67; P = 0.92). No significant difference was detected in either hospital (MD 1.56; 95% CI -1.43–4.55; P = 0.31) or ICU LOS (MD 0.75; 95% CI -0.36–1.86; P = 0.18) between the two groups. A sensitivity analysis revealed that administering IVIG may harmful to patients with moderate to severe ARDS induced by SARS-CoV-2 (OR 2.24; 95% CI 1.09–4.63; P = 0.03). The high level of heterogeneity remained substantial after multiple sensitivity and subgroup analyses were performed. The TSA indicated a lack of sufficient evidence to draw decisive conclusions from the current results since the required information size (RIS) of 8,373 still not reached yet.Conclusions: Current evidence do not support the use of IVIG in treatment for critically ill patients with COVID-19. Further prospective study with well design urgently needed for conclusive findings.