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

Abstract

ImportanceCOVID-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.ObjectiveTo compare the reactogenicity and immunogenicity of COVID-19 and influenza vaccinations administered together with those of COVID-19 vaccination alone.Design, Setting, and ParticipantsThis 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.ExposuresReceiving COVID-19 vaccine, influenza vaccine, or both.Main Outcomes and MeasuresThe 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.ResultsThis 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 RelevanceIn 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.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women

“…Additionally, previous research also suggested that the combined administration of the COVID-19 vaccine and the influenza vaccine is safe [ 34 , 35 ]. Therefore, as per the WHO recommendation, combined vaccination was a feasible option to increase coverage rates [ 36 ].…”

No immunological interference or concerns about safety when seasonal quadrivalent influenza vaccine is co-administered with a COVID-19 mRNA-1273 booster vaccine in adults: A randomized trial

“… 32–34 On the other hand, three non-randomized studies conducted in healthcare workers showed between 16% and 25% reductions in anti-S antibodies when mRNA-1273 or BNT162b2mRNA was co-administered with QIVs. 37 , 38 , 40 Two of the studies used a preference-based study design that allowed individuals to choose if they received co-administered QIV. An observational study of vaccine efficacy that also used a preference-based design showed that co-administration had no effect on the risk of breakthrough SARS-CoV-2 infections.…”

“… The results support co-administration recommendations Radner et al 37 Open label, non-randomized Co-administration vs administration alone Healthcare workers mRNA (Pfizer- BioNtech) Inactivated quadrivalent Descriptive 24% decrease in anti-S titers Reactogenicity was similar in the COVID-19 alone and co-administration groups and lower in the influenza vaccine alone group. Concomitant administration raised no safety concerns but provides evidence of reduced immunogenicity Gonen et al 38 Prospective cohort Self-selected for co-administration Healthcare workers mRNA (Pfizer- BioNtech) Inactivated quadrivalent Descriptive 16% decrease in anti-S titers Reactogenicity was similar in the COVID-19 alone and co-administration groups and lower in the influenza vaccine alone group. Reactogenicity and immunogenicity were mostly unchanged with co-administration Moscara et al 39 Prospective observational Self-selected for co-administration Healthcare workers mRNA (Pfizer-BioNtech) Cellular inactivated quadrivalent Effectiveness against symptomatic SARS-CoV-2 infection Not assessed Reactogenicity was similar in the COVID-19 alone and co-administration cohorts and lower in those who received influenza vaccine alone.…”

Ipsilateral and contralateral coadministration of influenza and COVID-19 vaccines produce similar antibody responses

“…A 2022 systematic review of the safety and immunogenicity of coadministered influenza and COVID-19 vaccines did not identify evidence of immune interference, 3 but this conclusion was based on data from only three studies. 4 , 5 , 6 Subsequent coadministration studies have yielded inconsistent results, but differences between groups were minimal, 7 , 8 , 9 , 10 and most studies compared vaccine coadministration with single vaccine administration rather than sequential vaccination (i.e., with an interval of 1–2 weeks between doses). 5 , 8 , 9 …”

“… 4 , 5 , 6 Subsequent coadministration studies have yielded inconsistent results, but differences between groups were minimal, 7 , 8 , 9 , 10 and most studies compared vaccine coadministration with single vaccine administration rather than sequential vaccination (i.e., with an interval of 1–2 weeks between doses). 5 , 8 , 9 …”