Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis
Authors: Siemieniuk Reed AC , Bartoszko Jessica J , Díaz Martinez Juan Pablo , Kum Elena , Qasim Anila , Zeraatkar Dena , Izcovich Ariel , Mangala Sophia , Ge Long , Han Mi Ah , Agoritsas Thomas , Arnold Donald , Ávila Camila , Chu Derek K , Couban Rachel , Cusano Ellen , Darzi Andrea J , Devji Tahira , Foroutan Farid , Ghadimi Maryam , Khamis Assem , Lamontagne Francois , Loeb Mark , Miroshnychenko Anna , Motaghi Sharhzad , Murthy Srinivas , Mustafa Reem A , Rada Gabriel , Rochwerg Bram , Switzer Charlotte , Vandvik Per O , Vernooij Robin WM , Wang Ying , Yao Liang , Guyatt Gordon H , Brignardello-Petersen Romina 
Published: September 2021

Abstract

Objective
To evaluate the efficacy and safety of antiviral antibody therapies and blood products for the treatment of novel coronavirus disease 2019 (covid-19).

Design
Living systematic review and network meta-analysis, with pairwise meta-analysis for outcomes with insufficient data.

Data sources
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, and six Chinese databases (up to 21 July 2021).

Study selection
Trials randomising people with suspected, probable, or confirmed covid-19 to antiviral antibody therapies, blood products, or standard care or placebo. Paired reviewers determined eligibility of trials independently and in duplicate.

Methods
After duplicate data abstraction, we performed random effects bayesian meta-analysis, including network meta-analysis for outcomes with sufficient data. We assessed risk of bias using a modification of the Cochrane risk of bias 2.0 tool. The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We meta-analysed interventions with ≥100 patients randomised or ≥20 events per treatment arm.

Results
As of 21 July 2021, we identified 47 trials evaluating convalescent plasma (21 trials), intravenous immunoglobulin (IVIg) (5 trials), umbilical cord mesenchymal stem cells (5 trials), bamlanivimab (4 trials), casirivimab-imdevimab (4 trials), bamlanivimab-etesevimab (2 trials), control plasma (2 trials), peripheral blood non-haematopoietic enriched stem cells (2 trials), sotrovimab (1 trial), anti-SARS-CoV-2 IVIg (1 trial), therapeutic plasma exchange (1 trial), XAV-19 polyclonal antibody (1 trial), CT-P59 monoclonal antibody (1 trial) and INM005 polyclonal antibody (1 trial) for the treatment of covid-19. Patients with non-severe disease randomised to antiviral monoclonal antibodies had lower risk of hospitalisation than those who received placebo: casirivimab-imdevimab (odds ratio (OR) 0.29 (95% CI 0.17 to 0.47); risk difference (RD) −4.2%; moderate certainty), bamlanivimab (OR 0.24 (0.06 to 0.86); RD −4.1%; low certainty), bamlanivimab-etesevimab (OR 0.31 (0.11 to 0.81); RD −3.8%; low certainty), and sotrovimab (OR 0.17 (0.04 to 0.57); RD −4.8%; low certainty). They did not have an important impact on any other outcome. There was no notable difference between monoclonal antibodies. No other intervention had any meaningful effect on any outcome in patients with non-severe covid-19. No intervention, including antiviral antibodies, had an important impact on any outcome in patients with severe or critical covid-19, except casirivimab-imdevimab, which may reduce mortality in patients who are seronegative.

Conclusion
In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescent plasma, IVIg, and other antibody and cellular interventions may not confer any meaningful benefit.

Systematic review registration
This review was not registered. The protocol established a priori is included as a data supplement.

Funding
This study was supported by the Canadian Institutes of Health Research (grant CIHR- IRSC:0579001321).

Readers’ note

This article is a living systematic review that will be updated to reflect emerging evidence. Interim updates and additional study data will be posted on our website (
www.covid19lnma.com
).