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The Safety and Immunogenicity of Concomitant Administration of COVID-19 Vaccines (ChAdOx1 or BNT162b2) with Seasonal Influenza Vaccines in Adults: A Phase IV, Multicentre Randomised Controlled Trial with Blinding (ComFluCOV)

36 Pages Posted: 30 Sep 2021

See all articles by Rajeka Lazarus

Rajeka Lazarus

University Hospitals Bristol - University Hospitals Bristol and Weston NHS Foundation Trust

Sarah Baos

University of Bristol

Heike Cappel-Porter

University Hospitals Bristol

Andrew Carson-Stevens

Cardiff University

Madeleine Clout Clout

University of Bristol

Lucy Culliford

University Hospitals Bristol

Stevan R Emmett

Government of the United Kingdom - Royal United Hospitals Bath NHS Foundation Trust

Jonathan Garstang

Government of the United Kingdom - National Health Service (NHS)

Lukuman Gbadamoshi

Government of the United Kingdom - Royal United Hospitals Bath NHS Foundation Trust

Bassam Hallis

Public Health England - National Infection Service

Rosie A Harris

University of Bristol

David Hutton

University of Bristol

Nick Jacobsen

University of Bristol

Katherine Joyce

University of Bristol

Rachel Kaminski

National Health Service, United Kingdom

Vincenzo Libri

NIHR UCLH Clinical Research Facility

Alexander Middleditch

University Hospitals Bristol - University Hospitals Bristol and Weston NHS Foundation Trust

Liz McCullagh

University Hospitals Bristol - University Hospitals Bristol NHS Foundation Trust

Ed Moran

Government of the United Kingdom - National Health Service (NHS)

Adrian Phillipson

Government of the United Kingdom - National Health Service (NHS)

Elizabeth Price

Government of the United Kingdom - Great Western Hospitals

John Ryan

The Alverton Practice

Russell Thirard

University of Bristol

Rachel Todd

University of Bristol

Matthew D. Snape

University of Oxford - Oxford Vaccine Group

David Tucker

Government of the United Kingdom - National Health Service (NHS)

Rachel Williams

Government of the United Kingdom - National Health Service (NHS)

Jonathan S. Nguyen-Van-Tam

University of Nottingham - Division of Epidemiology and Public Health

Adam Finn

University Hospitals Bristol and Weston NHS Foundation Trust; University of Bristol - Cellular and Molecular Medicine

Chris Rogers

University of Bristol

ComfluCOV Trial Group

Independent

More...

Abstract

Background: Concomitant administration of COVID-19 and influenza vaccines would reduce burden on healthcare systems. We assess the safety of concomitant administration. 

Methods: Adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomised 1:1 to receive concomitant administration of either age-appropriate influenza or placebo alongside second COVID-19 vaccine. Three weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed to six weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted (aTIV) or a cellular or recombinant quadrivalent vaccine (QIVc/QIVr)). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reaction in the seven days after first trial vaccination(s), with a difference of <25% considered non-inferior. Local and unsolicited systemic reactions and humoral responses were also assessed (ISRCTN14391248). 

Findings: Between 1st April and 26th June 2021, 679 participants were recruited to one of six cohorts: (129 ChAdOx1/QIVc; 139 BNT162b2/QIVc; 146 ChAdOx1/aTIV; 79 BNT162b2/aTIV; 128 ChAdOx1/QIVr; 58 BNT162b2/QIVr). Overall, 340 participants were randomised to concomitant administration of influenza and COVID-19 vaccine and 339 were randomised to placebo and COVID-19 vaccine. Non-inferiority was indicated in four cohorts; ChAdOx1/QIVc: risk difference (influenza vaccine minus placebo) -1·29% (95% confidence interval (CI) ‑14·7%, 12·1%); BNT162b2/QIVc: 6·17% (‑6·27%, 18·6%); BNT162b2/aTIV: -12·9% (‑34·2%, 8·37%); ChAdOx1/QIVr: 2·53% (‑13·3%, 18·3%). In two cohorts the upper limit of the 95%CI exceeded 25%; ChAdOx1/aTIV: 10·3% (‑5·44%, 26·0%) and BNT162b2/QIVr: 6·75% (‑11·8%, 25·3%). Most reactions were mild or moderate. Rates of local and unsolicited systemic reactions were similar between randomised groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected. 

Interpretation: Concomitant vaccination raises no safety concerns and preserves the immune response to both vaccines.

Clinical Trial Registration Details: The trial is registered (ISRCTN14391248)

Funding Information: The trial is commissioned and funded by the Department of Health and Social Care (DHSC) through the National Institute for Health Research (NIHR). This research was supported by the Vaccine Task Force (VTF) and NIHR Policy Research Programme (PR-R17-0916-22001, NIHR203243).

Declaration of Interest: RL reports grants from National Institute for Health Research during the conduct of the trial, and grants from Elizabeth Blackwell Institute, AstraZeneca, Janssen and Valneva outside the submitted work. CR reports grants from National Institute for Health Research, during the conduct of the trial. JSN-V-T reports he is seconded to the Department of Health and Social Care, England. AF reports grants from Pfizer during the conduct of the trial, and grants from Elizabeth Blackwell Institute, Gates Foundation, Sanofi Pasteur, VBI Vaccines, Pfizer, Janssen, GSK, MedImmune, Novavax and Valneva outside the submitted work. Between May 2015 and May 2019 AF was President of the European Society for Paediatric Infectious Diseases which, during this period, received sponsorship from GSK for its annual congress. He currently serves as chief investigator on the Valneva (Covid-19) vaccine phase 1/2 and 2/3 studies .He also serves as co-investigator on the Janssen (Covid-19) vaccine 2 dose phase 3 study. He does advisory work related to vaccines for the UK government, the World Health Organisation and several companies developing vaccines. He also leads clinical trials of vaccines funded by the UK government, charities and vaccine manufacturers. He receives no personal remuneration or benefits in kind for any of this work apart from his salary via the University of Bristol from the Higher Education Funding Council and the NHS. He is a member of the UK Department of Health’s Joint Committee on Vaccination, Chair of the WHO European Technical Advisory Group of Experts in which capacity he attends SAGE. AM reports grants from National Institute for Health Research during the conduct of the trial, and grants from AstraZeneca, Janssen and Valneva outside the submitted work. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers, including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax, Pfizer, Janssen, Medimmune and MCM. The views in this paper are those of its authors and not necessarily those of the DHSC.

Ethical Approval Statement: Approvals were received from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number 2021-001124-18) and the South-Central Berkshire Research Ethics Committee (21/SC/0100).

Keywords: Concomitant vaccination, COVID-19 vaccine, Influenza vaccine, Clinical Trial

Suggested Citation

Lazarus, Rajeka and Baos, Sarah and Cappel-Porter, Heike and Carson-Stevens, Andrew and Clout, Madeleine Clout and Culliford, Lucy and Emmett, Stevan R and Garstang, Jonathan and Gbadamoshi, Lukuman and Hallis, Bassam and Harris, Rosie A and Hutton, David and Jacobsen, Nick and Joyce, Katherine and Kaminski, Rachel and Libri, Vincenzo and Middleditch, Alexander and McCullagh, Liz and Moran, Ed and Phillipson, Adrian and Price, Elizabeth and Ryan, John and Thirard, Russell and Todd, Rachel and Snape, Matthew D. and Tucker, David and Williams, Rachel and Nguyen-Van-Tam, Jonathan S. and Finn, Adam and Rogers, Chris and Group, ComfluCOV Trial, The Safety and Immunogenicity of Concomitant Administration of COVID-19 Vaccines (ChAdOx1 or BNT162b2) with Seasonal Influenza Vaccines in Adults: A Phase IV, Multicentre Randomised Controlled Trial with Blinding (ComFluCOV). Available at SSRN: https://ssrn.com/abstract=3931758 or http://dx.doi.org/10.2139/ssrn.3931758

Rajeka Lazarus (Contact Author)

University Hospitals Bristol - University Hospitals Bristol and Weston NHS Foundation Trust ( email )

Bristol
United Kingdom

Sarah Baos

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Heike Cappel-Porter

University Hospitals Bristol ( email )

Bristol, NHS Trust
United Kingdom

Andrew Carson-Stevens

Cardiff University ( email )

Aberconway Building
Colum Drive
Cardiff, Wales CF10 3EU
United Kingdom

Madeleine Clout Clout

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Lucy Culliford

University Hospitals Bristol ( email )

Bristol, NHS Trust
United Kingdom

Stevan R Emmett

Government of the United Kingdom - Royal United Hospitals Bath NHS Foundation Trust ( email )

United Kingdom

Jonathan Garstang

Government of the United Kingdom - National Health Service (NHS) ( email )

London, SW1A 2NS
United Kingdom

Lukuman Gbadamoshi

Government of the United Kingdom - Royal United Hospitals Bath NHS Foundation Trust ( email )

United Kingdom

Bassam Hallis

Public Health England - National Infection Service ( email )

United Kingdom

Rosie A Harris

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

David Hutton

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Nick Jacobsen

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Katherine Joyce

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Rachel Kaminski

National Health Service, United Kingdom ( email )

Vincenzo Libri

NIHR UCLH Clinical Research Facility

London
United Kingdom

Alexander Middleditch

University Hospitals Bristol - University Hospitals Bristol and Weston NHS Foundation Trust ( email )

Bristol
United Kingdom

Liz McCullagh

University Hospitals Bristol - University Hospitals Bristol NHS Foundation Trust ( email )

Bristol
United Kingdom

Ed Moran

Government of the United Kingdom - National Health Service (NHS) ( email )

London, SW1A 2NS
United Kingdom

Adrian Phillipson

Government of the United Kingdom - National Health Service (NHS) ( email )

London, SW1A 2NS
United Kingdom

Elizabeth Price

Government of the United Kingdom - Great Western Hospitals

Swindon
United Kingdom

John Ryan

The Alverton Practice

Penzance
United Kingdom

Russell Thirard

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Rachel Todd

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

Matthew D. Snape

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

David Tucker

Government of the United Kingdom - National Health Service (NHS) ( email )

London, SW1A 2NS
United Kingdom

Rachel Williams

Government of the United Kingdom - National Health Service (NHS) ( email )

London, SW1A 2NS
United Kingdom

Jonathan S. Nguyen-Van-Tam

University of Nottingham - Division of Epidemiology and Public Health

University Park
Nottingham, NG8 1BB
United Kingdom

Adam Finn

University Hospitals Bristol and Weston NHS Foundation Trust

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

University of Bristol - Cellular and Molecular Medicine ( email )

United Kingdom

Chris Rogers

University of Bristol ( email )

University of Bristol,
Senate House, Tyndall Avenue
Bristol, BS8 ITH
United Kingdom

ComfluCOV Trial Group

Independent

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