Immune-based therapy for hospitalized patients with COVID-19 and risk of secondary infections: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.

Objectives: The objective of this study is to systematically review the evidence for the effect of immune-based therapy in patients hospitalized with COVID-19 on the risk of secondary infections.

Search Methods: A search was executed by an expert searcher/librarian on the following databases in October 2020, and updated in January 2021: OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library including Clinical trial.gov, PROSPERO, and using controlled vocabulary (eg: MeSH, Emtree, etc) and key words representing the concepts "Covid 19” and “immunotherapies” and “outcomes including secondary infections.”

Registration: The protocol is registered with PROSPERO CRD4202122940

Eligibility criteria: We included randomized controlled trial (RCT) and non-randomized studies (NRS), in which adults, hospitalized with COVID-19 were treated with immunotherapy versus standard of care or placebo and had infectious complications as an outcome. We extracted data in duplicate an independent manner. We used RevMan 5.3 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 I2 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.

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 (I2=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 (I2= 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.