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Randomised Clinical Trials of COVID-19 Vaccines: Do Adenovirus-Vector Vaccines Have Beneficial Non-Specific Effects?

21 Pages Posted: 5 Apr 2022

See all articles by Christine Stabell Benn

Christine Stabell Benn

University of Southern Denmark - Odense Patient Data Explorative Network (OPEN); Bandim Health Project, INDEPTH Network

Frederik Schaltz-Buchholzer

Statens Serums Institut - Bandim Health Project

Sebastian Nielsen

University of Southern Denmark - Odense Patient Data Explorative Network (OPEN)

Mihai G. Netea

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI); Radboud University Nijmegen - Department of Internal Medicine

Peter Aaby

Bandim Health Project, INDEPTH Network; Bandim Health Institute - OPEN, Institute of Clinical Research

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Abstract

To examine the possible non-specific effects (NSEs) of the novel COVID-19 vaccines, we reviewed the randomised control trials (RCTs) of mRNA and adenovirus-vector COVID-19 vaccines reporting overall mortality, including COVID-19 deaths, accident deaths, cardiovascular deaths and other non-COVID-19 deaths. For overall mortality, with 74,193 participants and 61 deaths (mRNA:31; placebo:30), the relative risk (RR) for the two mRNA vaccines compared with placebo was 1.03 (95% CI=0.63-1.71). In the adenovirus-vector vaccines there were 122,164 participants and 46 deaths (vaccine:16; controls:30). The RR for adenovirus-vector vaccines versus placebo/control vaccine was 0.37 (0.19-0.70). The adenovirus-vector vaccines were associated with protection against COVID-19 deaths (RR=0.11 (0.02-0.87)) and non-accident, non-COVID-19 deaths (RR=0.38 (0.17-0.88)). The two types of vaccines differed significantly with respect to impact on overall mortality (p=0.030) as well as non-accident, non-COVID-19 deaths (p=0.046). The placebo controlled RCTs of COVID-19 vaccines were halted rapidly due to clear effects on COVID-19 infections. However, the data presented here argue for performing RCTs of mRNA and adeno-vectored vaccines head-to-head comparing long-term effects on overall mortality.

Funding: The work on the non-specific effects of vaccines was supported by private donations from Dr. Allan Schapira. The work on non-specific effects of vaccines has previously been supported by the Danish Council for Development Research, Ministry of Foreign Affairs, Denmark [grant number 104.Dan.8.f.], Novo Nordisk Foundation and European Union FP7 support for OPTIMUNISE (grant: Health-F3-2011-261375). CSB held a starting grant from the ERC (ERC-2009- StG-243149). CVIVA was supported by a grant from the Danish National Research Foundation (DNRF108). PA held a research professorship grant from the Novo Nordisk Foundation.

Declaration of Interest: Nothing to declare

Keywords: Adenovirus-vector vaccines, COVID-19 vaccines, mRNA vaccines, non-specific effects of vaccines

Suggested Citation

Benn, Christine Stabell and Schaltz-Buchholzer, Frederik and Nielsen, Sebastian and Netea, Mihai G. and Netea, Mihai G. and Aaby, Peter, Randomised Clinical Trials of COVID-19 Vaccines: Do Adenovirus-Vector Vaccines Have Beneficial Non-Specific Effects?. Available at SSRN: https://ssrn.com/abstract=4072489 or http://dx.doi.org/10.2139/ssrn.4072489

Christine Stabell Benn

University of Southern Denmark - Odense Patient Data Explorative Network (OPEN) ( email )

J. B. Winsløws Vej 4
Odense
Denmark

Bandim Health Project, INDEPTH Network ( email )

Bissau
Guinea-Bissau

Frederik Schaltz-Buchholzer

Statens Serums Institut - Bandim Health Project ( email )

Denmark

Sebastian Nielsen

University of Southern Denmark - Odense Patient Data Explorative Network (OPEN) ( email )

Denmark

Mihai G. Netea

Radboud University Nijmegen - Department of Internal Medicine ( email )

Nijmegen
Netherlands

Radboud University Nijmegen - Radboud Center for Infectious Diseases (RCI)

Nijmegen
Netherlands

Peter Aaby (Contact Author)

Bandim Health Project, INDEPTH Network ( email )

Bissau
Guinea-Bissau

Bandim Health Institute - OPEN, Institute of Clinical Research ( email )

Odense
Denmark

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