Immunogenicity and safety of coadministration of COVID-19 and influenza vaccination

Abstract

Seasonal influenza vaccination is established as important infection prevention measure, especially among highly exposed healthcare workers (HCWs) [1]. Coadministration with the third dose of COVID-19 vaccine could be an efficient strategy protecting HCWs from two major viral respiratory infections [2][3][4]. To date, the humoral immunogenicity and side-effects of a coadministered third COVID-19 and a seasonal quadrivalent influenza vaccine are still unclear, and the available data is limited in transferability to the general public [5][6][7]. This preference-based non-randomised controlled study examines the antibody-mediated immunogenicity and vaccine-related side-effects of mRNA-based COVID-19 and seasonal influenza vaccine coadministration in HCWs.1231 participants of the CoVacSer study with two doses of BNT162b2mRNA (30 µg mRNA each) as basic COVID-19 immunisation received a third dose of mRNA-based COVID-19 vaccine administering BNT162b2mRNA (30 µg mRNA) or mRNA-1273 (50 µg mRNA) depending on age and vaccine availability. HCWs could opt for a simultaneous influenza vaccine coadministration (Influvac Tetra vaccine 2021/2022) injected intramuscularly into the opposite arm. HCWs without coadministration received either no seasonal influenza vaccination or at least 14 days apart from the COVID-19 booster. Convalescent HCWs having passed a PCR-confirmed SARS-CoV-2 infection were excluded.Pseudonymised serum blood samples combined with a questionnaire were collected from 1 October 2021 to 31 January 2022 between 14 and 90 days after the COVID-19 vaccination. Anti-SARS-CoV-2-spike IgG levels were obtained using the SERION ELISA agile SARS-CoV-2 IgG (SERION diagnostics, Wuerzburg, Germany) [8].The statistical analyses were performed with R (version 3.1.2) on logarithmised anti-SARS-CoV-2-spike IgG concentrations based on a multiple linear regression analysis. The parameters including potential influencing factors were estimated using a generalised least squares fit (R package nlme) [9,10]. Statistical subgroup differences of the independent categorical variables were calculated with the estimated marginal means. Using the Tukey test statistics, pairwise post hoc tests were performed to expose statistically significant differences. The emmeans package was used to estimate marginal means and to calculate pairwise differences [11]. Investigating the role of side-effects, pairwise Fisher exact tests were performed. To correct against multiple testing, p-values were adjusted using the Benjamini-Yekutielie procedure [12]. Only adjusted p-values below a significance level of 0.05 were considered statistically significant.The study protocol was approved by the ethics committee of the University of Wuerzburg in accordance with the Declaration of Helsinki (file number 79/21). 20.2% (249/1231) of all participants opted for coadministration, whereas 90.4% (225/249) received BNT162b2mRNA and 9.6% (24/249) mRNA-1273 as COVID-19 booster vaccine. 79.8% (982/1231) of all participants were vaccinated with a mRNA-based COVID-19 vacci...

Immunogenicity and Reactogenicity of Coadministration of COVID-19 and Influenza Vaccines

“…Of the 3 study groups, those who received SIV alone experienced the least reactogenicity, while COVID-19 vaccination alone elicited similar reactogenicity to that of the coadministration of COVID-19 vaccine with SIV. These findings are similar to those of trials that investigated the coadministration of SIV and COVID-19 vaccines and found that coadministration of both vaccine groups was similar to COVID-19 vaccination alone in terms of adverse reactions …”

“…These findings are similar to those of trials that investigated the coadministration of SIV and COVID-19 vaccines and found that coadministration of both vaccine groups was similar to COVID-19 vaccination alone in terms of adverse reactions. 4,5,[7][8][9] When assessing immunogenicity, we estimated a mild decrease in anti-spike IgG titers, with a point estimate of 16%, and a confidence interval not greater than 31%. Findings from previous immunogenicity and correlates of protection studies suggest that changes in IgG titers to such an extent did not greatly impact vaccine effectiveness, 13 vaccine effectiveness against substantially symptomatic disease, 14 or a SARS-CoV-2 diagnosis risk.…”

“…Current literature has conflicting reports regarding immunogenicity of COVID-19 vaccines when administered together with SIV. Some studies reported a significant decrease in postvaccination titers 9,16 or reduced neutralization, 8 while others found that the humoral response was similar between coadministration and COVID-19 vaccination alone. 4,5 When looking into the current literature on the coadministration of these 2 vaccines, trials investigated the coadministration of several different types of COVID-19 vaccines.…”

Comparative effectiveness of the monovalent XBB.1.5-containing covid-19 mRNA vaccine across three Nordic countries

“…In addition, this also means that our main estimates primarily reflect the co-administration with the seasonal influenza vaccine. This is reassuring, since coadministration has been speculated to blunt the immune response, [14][15][16][17][18][19] and if that is the case, our estimates are likely conservative.…”

Bivalent BNT162b2 mRNA original/omicron BA.4-5 booster vaccination: adverse reactions and inability to work compared with the monovalent COVID-19 booster

“…Study participants administered with a different COVID-19 vaccine as second booster were excluded. As coadministration of COVID-19 and influenza vaccination might influence immunogenicity and side effects,( 4 ) individuals receiving a simultaneous influenza vaccination were also excluded.…”