Efficacy and safety of three passive immunotherapies for Corona Virus Disease 2019：a system review and network meta-analysis
Authors: Xu Yonghao , Chen Yubiao , Ling Zhaoyi , Zhang Jie , Zhang Yu , Zeng Yuan , Pan Yaru , Li Yuchong , Xi Yin , Li Yimin , Huang Yongbo , Liu Xiaoqing 
Published: October 2022

Background
Passive immunotherapies to augment the humoral immunity against virus have been associated with prevention of severe illnesses and reduction of mortality of patients with coronavirus disease 2019 (COVID-19). However, less is known about the comparative effectiveness of different types of passive immunotherapies. The aim of this study is to compare efficacy and safety of passive immunotherapy in patients with COVID-19.
Methods
This is a two-part network meta-analysis which evaluate the efficacy of passive immunotherapy in outpatients and hospitalized patients separately. Electronic databases, including PubMed, EMBASE, and Cochrane CENTRAL were systematically searched for articles published before 26th April 2022. Randomized clinical trials that compared COVID-19 specific antiviral antibodies, convalescence plasma and hyperimmune anti-COVID-19 Intravenous Immunoglobulin with placebo, or control plasma, or standard of care in patients with COVID-19 were included. Two authors screened the studies independently. We extracted data and assessed the risk of bias of studies using the revised Cochrane risk of bias tool (RoB 2 tool) at study level. The primary outcome for outpatients is hospitalization within 30 days from randomization and are mortality, need of invasive mechanical ventilation, and severe advent events for hospitalized patients.
Results
In this systematic review and network meta-analysis, data were pooled from 41 eligible randomized control trials involving 42298 participants. In the first part of network meta-analysis which is consist of 9 eligible trials with 10093 participants, compared with control, specific antiviral antibodies (odds ratio [OR]: 0.22, 95% CI: 0.16, 0.28) rather than CP (OR: 0.75, 95%CI: 0.56, 1.01) reduced the risk of hospitalization; treatment with antibody reduced a greater risk of hospitalization (OR: 0.29, 95%CI: 0.19, 0.43) when compared with CP. For the analysis of secondary outcome in outpatients, antibody (OR: 0.10, 95%CI: 0.01, 0.37) rather than CP (OR: 0.81, 95%CI: 0.23, 2.78) reduced the risk of mortality. In the second party of meta-analysis, none of the passive immunotherapy was associated with the reduction of mortality, need of invasive mechanical ventilation and severe adverse events. Furthermore, none of passive immunotherapy was associated with improvement in 6 secondary outcomes. However, in subgroup analysis, the administration of antibody was associated with improvement of mortality, need of invasive mechanical ventilation, rate of discharge, duration of hospital stay, time to death and with less adverse events.
Conclusions
In this network meta-analysis of clinical trials of patients with COVID-19, we found that treatment with antiviral antibodies reduced the risk of hospitalization in outpatients. Among hospitalized adult patients, all three passive immunotherapies compared with control did not result in a statistically significant improvement of the primary outcomes, but use of neutralizing antibodies may lead to improvement of primary outcomes and key secondary outcomes in seronegative patients. Further development of broader-spectrum antibodies targeting to highly conserved domain of spike protein which avoids immune escape of new variants are needed.