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Antibody and cellular therapies for treatment of covid-19 : a living systematic review and network meta-analysis Siemieniuk, Reed A. C.; Bartoszko, Jessica J.; Martinez, Juan Pablo Díaz; Kum, Elena; Qasim, Anila; Zeraatkar, Dena; Izcovich, Ariel; Mangala, Sophia; Ge, Long; Han, Mi Ah; et al.
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).
Item Metadata
| Title |
Antibody and cellular therapies for treatment of covid-19 : a living systematic review and network meta-analysis
|
| Creator |
Siemieniuk, Reed A. C.; Bartoszko, Jessica J.; Martinez, Juan Pablo Díaz; 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 W. M.; Wang, Ying; Yao, Liang; Guyatt, Gordon H.; Brignardello-Petersen, Romina
|
| Publisher |
BMJ Publishing Group
|
| Date Issued |
2021-09-10
|
| Description |
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).
|
| Genre | |
| Type | |
| Language |
eng
|
| Date Available |
2021-10-29
|
| Provider |
Vancouver : University of British Columbia Library
|
| Rights |
Attribution-NonCommercial 4.0 International
|
| DOI |
10.14288/1.0402762
|
| URI | |
| Affiliation | |
| Citation |
Siemieniuk, Reed AC et al. Antibody and cellular therapies for treatment of covid-19: A living systematic review and network meta-analysis. (2021). BMJ (Online), 374, n2231-n2231.
|
| Publisher DOI |
10.1136/bmj.n2231
|
| Peer Review Status |
Reviewed
|
| Scholarly Level |
Faculty; Researcher; Postdoctoral; Graduate; Other
|
| Copyright Holder |
Authors
|
| Rights URI | |
| Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial 4.0 International