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

Key Points

Question

Is the coadministration of a COVID-19 vaccine with a seasonal influenza vaccine safe and efficacious?

Findings

This prospective cohort study included health care workers vaccinated against COVID-19 and/or influenza. Compared with COVID-19 vaccination alone, the risk of systemic symptoms was lower and statistically insignificant in the coadministration group. Lower, statistically insignificant anti-spike IgG titers were found in the coadministration group.

Meaning

In this study, both reactogenicity and immunogenicity were mostly unchanged with coadministration of the COVID-19 and season influenza vaccines compared with the administration of COVID-19 vaccination alone.

Abstract

This cohort study compares the reactogenicity and immunogenicity of COVID-19 and influenza vaccinations administered together with those of COVID-19 vaccination alone.

Abstract

Importance

COVID-19 and seasonal influenza vaccines were previously given separately, although their coadministration is warranted for vaccination adherence. Limited data on their coadministration have been published.

Objective

To compare the reactogenicity and immunogenicity of COVID-19 and influenza vaccinations administered together with those of COVID-19 vaccination alone.

Design, Setting, and Participants

This prospective cohort study included health care workers at a large tertiary medical center in Israel who received the Influvac Tetra (Abbott) influenza vaccine (2022/2023), the Omicron BA.4/BA.5–adapted bivalent (Pfizer/BioNTech) vaccine, or both. Vaccination began in September 2022, and data were collected until January 2023. Vaccines were offered to all employees and were coadministered or given separately. Adverse reaction questionnaires were sent, and serologic samples were also collected.

Exposures

Receiving COVID-19 vaccine, influenza vaccine, or both.

Main Outcomes and Measures

The main outcomes for the reactogenicity analysis were symptoms following vaccine receipt, assessed by a digital questionnaire: any local symptoms; fever; weakness or fatigue; any systemic symptoms; and their duration. The immunogenicity analysis’ outcome was postvaccination anti-spike IgG titer.

Results

This study included 2 cohorts for 2 separate analyses. The reactogenicity analysis included 588 participants (of 649 questionnaire responders): 85 in the COVID-19 vaccine–alone group (median [IQR] age, 71 [58-74] years; 56 [66%] female); 357 in the influenza vaccine–alone group (median [IQR] age, 55 [40-65] years; 282 [79%] female); and 146 in the coadministration group (median [IQR] age, 61 [50-71] years; 81 [55%] female). The immunogenicity analysis included 151 participants: 74 participants in the COVID-19 vaccine group (median [IQR] age, 67 [56-73] years; 45 [61%] female) and 77 participants in the coadministration group (median [IQR] age, 60 [49-73] years; 42 [55%] female). Compared with COVID-19 vaccination alone, the risk of systemic symptoms was similar in the coadministration group (odds ratio, 0.82; 95% CI, 0.43-1.56). Geometric mean titers in the coadministration group were estimated to be 0.84 (95% CI, 0.69-1.04) times lower than in the COVID-19 vaccine–alone group.

Conclusions and Relevance

In this cohort study of health care workers who received a COVID-19 vaccine, an influenza vaccine, or both, coadministration was not associated with substantially inferior immune response or to more frequent adverse events compared with COVID-19 vaccine administration alone, supporting the coadministration of these vaccines.