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

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 ).

Efficacy of High-Dose Polyclonal Intravenous Immunoglobulin in COVID-19: A Systematic Review

“…Regarding the main outcome "mortality", the use of IVIG was not associated with a significantly reduced risk of death, independently of COVID-19 severity or type of study (RCT or non-RCT). Such results are in accordance with a recently published living systematic review and network meta-analysis [35].…”

A Hybrid Soluble gp130/Spike-Nanobody Fusion Protein Simultaneously Blocks Interleukin-6 trans -Signaling and Cellular Infection with SARS-CoV-2

“…Antiviral antibodies are effective only very early in COVID-19 disease progression ( 67 ). In later stages of severe COVID-19, patients develop a hyperinflammatory state, which is associated with multiorgan damage and respiratory failure ( 4 ).…”

Ocular and Systemic Complications of COVID-19: Impact on Patients and Healthcare

“…In those at risk for progression, clinical trials have found that monoclonal antibodies including ritonavir, casirivimab, imdevimab, bamlanivimab, etesevimab, CT-P59, and sotrovimab were associated with decreased rates of hospitalization compared to placebos; however, only casirivimab-imdevimab was found in a meta-analysis to have moderate certainty evidence for reducing hospitalizations. 20 The combination of nirmatrelvir (SARS-CoV-2 main protease inhibitor) and ritonavir (HIV-1 protease inhibitor and CYP3A inhibitor) has gained emergency use approval by the Federal Drug Administration (Paxlovid, PF-07321332, Pfizer, New York, USA) for use in non-hospitalized patients with COVID-19 at high risk for progressing to severe illness to decrease the risk of hospitalization and death; in the phase 2/3 randomized double blind study, there was an 89% reduction in hospitalization and deaths compared to placebo. 21 In patients with severe or critical COVID-19, metaanalyses have found that glucocorticoids likely reduced the risk of death and mechanical ventilation and duration of hospitalization in admitted patients requiring oxygen support.…”

“… 26 In meta-analyses, antiviral antibodies and blood products like convalescent plasma and intravenous immunoglobulins were not associated with a reduction in mortality in those with severe disease. 20 , 27 , 28 The benefits of other treatments like favipiravir, azithromycin, lopinavir-ritonavir, umifenovir are under investigation. 22 …”