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Vaccines to Prevent COVID-19: A Living Systematic Review With Trial Sequential Analysis and Network Meta-Analysis of Randomised Controlled Trials

49 Pages Posted: 27 May 2021

See all articles by Steven Kwasi Korang

Steven Kwasi Korang

University of Copenhagen - Copenhagen Trial Unit

Elena von Rohden

University of Copenhagen - Copenhagen Trial Unit

Areti Angeliki Veroniki

University of Ioannina

Giok Ong

University of Oxford - John Radcliffe Hospital

Owen Ngalamika

University of Copenhagen - Copenhagen Trial Unit

Faiza Siddiqui

University of Copenhagen - Copenhagen Trial Unit

Sophie Juul

University of Copenhagen - Copenhagen Trial Unit

Emil Eik Nielsen

University of Copenhagen - Copenhagen Trial Unit

Joshua Buron Feinberg

University of Copenhagen - Copenhagen Trial Unit

Johanne Juul Petersen

University of Copenhagen - Copenhagen Trial Unit

Christian Legart

University of Copenhagen - Copenhagen Trial Unit

Afoke Kokogho

Walter Reed Army Institute of Research

Mathias Maagaard

University of Copenhagen - Copenhagen Trial Unit

Sarah Klingenberg

University of Copenhagen - Copenhagen Trial Unit

Lehana Thabane

McMaster University - Department of Health Research Methods, Evidence, and Impact (HEI)

Ariel Bardach

Instituto de Efectividad Clínica y Sanitaria - Centro de Investigación en Epidemiología y Salud Pública (IECS-CIESP)

Agustin Ciapponi

University of Copenhagen - Department of Immunology and Microbiology; Instituto de Efectividad Clínica y Sanitaria - Centro de Investigación en Epidemiología y Salud Pública (IECS-CIESP)

Allan Randrup Thomsen

University of Copenhagen - Department of Immunology and Microbiology

Janus C. Jakobsen

University of Copenhagen - Copenhagen Trial Unit

Christian Gluud

University of Copenhagen - Copenhagen Trial Unit

More...

Abstract

Background: COVID-19 is a rapidly spreading disease that is causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed. Several vaccines have been accepted by regulatory authorities, but their individual and relative efficacy and adverse effects remain unclear.

Methods: We conducted a systematic review of randomised clinical trials with network meta-analysis and Trial Sequential Analysis (TSA). Searches were made in CENTRAL, MEDLINE, Embase, and other sources from inception to May 12, 2021 for randomised clinical trials, assessing vaccines for COVID-19 . At least two independent reviewers screened studies, extracted data, and assessed the risk of bias. Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events.

Findings We identified 22 trials; 19 trials randomising 144 434 participants were included in our analyses. mRNA vaccines (efficacy 95%, 95% confidence interval (CI) 92% to 97%; 69 285 participants; 2 trials; GRADE: moderate certainty) and viral vector vaccines (efficacy 68%, 95% CI 61% to 74%; 71 401 participants; 5 trials; GRADE: low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio (RR) 0·25, 95% CI 0·09 to 0·67; 67 563 participants; 3 trials, GRADE: low certainty), but data on mRNA vaccines are still imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence indicated rare serious adverse events. mRNA and viral vector vaccines increased the risk of non-serious adverse events. 

Interpretation The evidence suggests that mRNA vaccines and viral vector vaccines are effective in preventing COVID-19. mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. mRNA vaccines and viral vector vaccines increase the risks of rare serious adverse events according to observational evidence. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines. 

Registration Information: PROSPERO CRD42020196492.

Funding Information: The Copenhagen Trial Unit funded the wages for the authors affiliated with the Copenhagen Trial Unit. None of the authors received any specific funding related to the review.

Declaration of Interests: The authors declare that they have no known competing interests.

Keywords: COVID-19, vaccine, SARS-CoV2, prevention, pandemic, systematic review, meta-analysis, network meta-analysis, Trial Sequential Analysis, GRADE

Suggested Citation

Korang, Steven Kwasi and von Rohden, Elena and Veroniki, Areti Angeliki and Ong, Giok and Ngalamika, Owen and Siddiqui, Faiza and Juul, Sophie and Nielsen, Emil Eik and Feinberg, Joshua Buron and Petersen, Johanne Juul and Legart, Christian and Kokogho, Afoke and Maagaard, Mathias and Klingenberg, Sarah and Thabane, Lehana and Bardach, Ariel and Ciapponi, Agustin and Thomsen, Allan Randrup and Jakobsen, Janus C. and Gluud, Christian, Vaccines to Prevent COVID-19: A Living Systematic Review With Trial Sequential Analysis and Network Meta-Analysis of Randomised Controlled Trials. Available at SSRN: https://ssrn.com/abstract=3854588 or http://dx.doi.org/10.2139/ssrn.3854588

Steven Kwasi Korang (Contact Author)

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark
+ 45 25 38 87 93 (Phone)

Elena Von Rohden

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Areti Angeliki Veroniki

University of Ioannina ( email )

Campus Psathaki
Ioannina, Epirus 48100
Greece

Giok Ong

University of Oxford - John Radcliffe Hospital ( email )

Oxford, Oxfordshire
United Kingdom

Owen Ngalamika

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Faiza Siddiqui

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Sophie Juul

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Emil Eik Nielsen

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Joshua Buron Feinberg

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Johanne Juul Petersen

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Christian Legart

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Afoke Kokogho

Walter Reed Army Institute of Research ( email )

Silver Spring, MD 20910
United States

Mathias Maagaard

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Sarah Klingenberg

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Lehana Thabane

McMaster University - Department of Health Research Methods, Evidence, and Impact (HEI) ( email )

Hamilton, Ontario L8N 3Z5
Canada

Ariel Bardach

Instituto de Efectividad Clínica y Sanitaria - Centro de Investigación en Epidemiología y Salud Pública (IECS-CIESP) ( email )

Agustin Ciapponi

University of Copenhagen - Department of Immunology and Microbiology ( email )

Copenhagen
Denmark

Instituto de Efectividad Clínica y Sanitaria - Centro de Investigación en Epidemiología y Salud Pública (IECS-CIESP) ( email )

Allan Randrup Thomsen

University of Copenhagen - Department of Immunology and Microbiology ( email )

Copenhagen
Denmark

Janus C. Jakobsen

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark

Christian Gluud

University of Copenhagen - Copenhagen Trial Unit ( email )

Blegdamsvej 9
Copenhagen Ø, 2100
Denmark