Immune-Based Therapy for Hospitalized Patients with COVID-19 and Risk of Secondary Infections: A Systematic Review and Meta-Analysis

Abstract

Background: Some immune-based therapies are efficacious in the treatment of patients with COVID-19 requiring hospitalization. However, safety concerns related to the potential risk of secondary infections may limit their use. We reviewed studies that assessed the risk of secondary infections with immune-based therapies in adult patients hospitalized with COVID-19.Methods: In this systematic review and meta-analysis we run a search in OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library, clinicaltrials.gov, PROSPERO in October 2020 and updated in January 2021. We included randomized controlled trial (RCT) and non-randomized studies (NRS), addressing the primary objective. We extracted data in duplicate an independent manner. We used RevMan to conduct a meta-analysis for RCTs and NRS using the random effects models to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) for the incidence of infection. Statistical heterogeneity was determined using the I 2 statistic. We assessed the risk of bias for all included studies and rated the certainty of evidence for each outcome using the GRADE approach. We conducted a meta-regression using the R package to meta-explore whether age, sex, and invasive mechanical ventilation modified the risk of infection with immune-based therapies. The protocol is registered with PROSPERO, CRD42021229406.Findings: We identified 74 eligible publications (16 RCT and 58 NRS). Due to high heterogeneity in NRS, we performed meta-analysis only for RCTs, which included 3403 participants (mean age 60 years and 63% male). Infection risk was lower with immune-based therapy (173/1906, 9.1% versus 210/1496, 14%; RR= 0.74 (95% CI, 0.58-0.96; p=0.02 and (I 2 =26 %). Subgroup analysis did not identify any subgroup effect by type of immune-based therapies (p=0.41). Meta-regression revealed no impact of age, sex or mechanical ventilation on the effect of immune-based therapies on the risk of infection. Pneumonia occurred in 65/1131 on immune-based therapy versus 99/998 with placebo; RR= 0.67 (95%CI 0.41-1.09; p=0.11) and (I 2 = 44%).Interpretation: We identified moderate certainty evidence that the use of immune-based therapies in COVID-19 reduces the risk of secondary infections as compared to standard of care in hospitalized patients with COVID-19.Funding Statement: None.Declaration of Interests: We declare no competing interests.