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Meta-Analysis
. 2021 Sep 23:374:n2231.
doi: 10.1136/bmj.n2231.

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis

Affiliations
Meta-Analysis

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis

Reed Ac Siemieniuk et al. BMJ. .

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).

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Canadian Institutes of Health Research for the submitted work; ML reports personal fees and non-financial support from Sanofi, grants and personal fees from Seqirus, personal fees from Pfizer, and personal fees from Medicago outside the submitted work, and is a co-investigator on ACT randomised trial of covid-19 therapy; LG reports grants from Ministry of Science and Technology of China outside the submitted work.

Figures

Fig 1
Fig 1
Study selection for inclusion in review of antibody and cellular therapies for treatment of covid-19
Fig 2
Fig 2
Summary of effects compared with standard care of antibody and cellular therapies for treatment of covid-19

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References

    1. Johns Hopkins University. Coronavirus resource center. 2020. https://coronavirus.jhu.edu/map.html.
    1. Cytel. Global coronavirus COVID-19 clinical trial tracker. 2020. https://www.covid19-trials.com/.
    1. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. Convalescent Plasma Study Group . The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis 2015;211:80-90. . 10.1093/infdis/jiu396 - DOI - PMC - PubMed
    1. Devasenapathy N, Ye Z, Loeb M, et al. . Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis. CMAJ 2020;192:E745-55. . 10.1503/cmaj.200642 - DOI - PMC - PubMed
    1. Bozzo J, Jorquera JI. Use of human immunoglobulins as an anti-infective treatment: the experience so far and their possible re-emerging role. Expert Rev Anti Infect Ther 2017;15:585-604. . 10.1080/14787210.2017.1328278 - DOI - PubMed

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