In a recent study published in JAMA Network Open, researchers investigated the comparative efficacy and safety of the simultaneous coronavirus disease 2019 (COVID-19) and seasonal influenza vaccination regimen compared to SARS-CoV-2 vaccination alone among healthcare workers (HCWs) who had received one or two COVID-19 booster doses.
Booster vaccinations are essential for HCWs who come into contact with people vulnerable to COVID-19 severity outcomes. In the initial days of the pandemic, several health groups advised that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza vaccines be administered individually.
In the influenza season between 2022 and 2023, however, health organizations such as the United States Centers for Disease Control and Prevention (US CDC) advised simultaneous administration of vaccinations to boost vaccination adherence and reduce the healthcare burden. However, data on SARS-CoV-2 and influenza co-vaccination are limited.
About the study
In the present prospective cohort study, researchers evaluated the immunogenicity and reactogenicity of SARS-CoV-2 and influenza co-vaccination compared to SARS-CoV-2 vaccination alone.
The study included HCWs working at the Sheba Medical Center (SMC) of Israel who had been administered the Influvac Tetra influenza vaccine (between 2022 and 2023), the SARS-CoV-2 Omicron BA.4/5 variant of concern (VOC)-encoding bivalent SARS-CoV-2 vaccine, individually or in combination. Vaccines were administered from September 2022 onwards, and information was obtained through January 2023.
The study participants filled out adverse drug reaction questionnaires and provided serum samples for the analysis. The outcome measures to analyze reactogenicity included symptoms developing post-vaccine administration, assessed based on digital questionnaires: fever, local symptoms, fatigue, weakness, systemic symptoms, and symptom duration. Post-vaccination anti-SARS-CoV-2 spike (S) immunoglobulin (Ig) geometric mean titers (GMTs) and geometric mean ratios (GMRs) were determined using the restricted cubic spline method to assess immunogenicity.
Multivariate logistic regression modeling was performed, and the odds ratios (ORs) were calculated. SARS-CoV-2 vaccines were administered from 28 September 2022 onwards, whereas seasonal influenza vaccines (SIVs) were administered from 12 October 2022 onwards at the SMC. For the reactogenicity and immunogenicity assessments, HCWs who received vaccines till 29 November and 29 December 2022, respectively, were included.
Reactogenicity was evaluated using electronic questionnaires distributed 62 days post-vaccination, addressing systemic and local symptoms. Individuals who received SARS-CoV-2 and/or SIV vaccinations during the period of the study and participated in the Sheba Medical Centre cohort were included in the analysis.
The team excluded immunosuppressed individuals, those who received SIV and SARS-CoV-2 vaccines on different days but less than a week apart, those who filled out the digital questionnaires within five days of vaccination, and those with incoherent or incomplete responses.
For the immunogenicity analysis, the team included individuals who had received SARS-CoV-2 vaccines and/or SIVs during the period of the study, those who participated in the Sheba Medical Centre serological study, and those who underwent serology tests within 40 days of or till 70 days after SARS-CoV-2 vaccination.
The team excluded individuals with immunosuppression, SARS-CoV-2 infection in the duration between receipt of the SARS-CoV-2 vaccine and post-vaccination serological testing, and the receipt of SIV and SARS-CoV-2 on different days but less than a week apart.
Compared to SARS-CoV-2 vaccinations alone, systemic symptom risk was lower but non-significant among co-vaccinated individuals with lower but non-significant anti-S IgG titers. The reactogenicity evaluation included 588 individuals (out of 649 respondents): 146 SARS-CoV-2 and influenza co-vaccinees [median age, 61 years; 55% (n=81) females]; 85 SARS-CoV-2 vaccinees [median age, 71 years; 66% (n=56) females]; and 357 influenza vaccinees [median age, 55 years; 79% (n=282) females].
The immunogenicity evaluation included 151 HCWs: 74 individuals in the SARS-CoV-2 vaccine cohort [median age, 67 years; 61% (n=45) females] and 77 individuals in the co-vaccination group [median age, 60 years; 55% (n=42) females]. Compared to SARS-CoV-2-only vaccinees, systemic symptom risk was comparable among co-vaccinated individuals (OR, 0.8). The estimated GMTs for the co-vaccination group were 0.8-fold lower than for the SARS-CoV-2 vaccine-only group.
During the 60 follow-up days for the immunogenicity group, none of the participants contracted SARS-CoV-2. The sensitivity analysis conducted included two healthcare workers who were removed from the primary analysis due to being diagnosed with COVID-19 during the period between receipt of the vaccine and post-vaccination serum testing, which showed that GMTs for the co-vaccinated group were 0.9 times lower compared to the SARS-CoV-2 vaccine-only group.
The incidence rates of systemic reactions in the SARS-CoV-2 vaccination-only, SIV vaccination-only, and co-vaccination groups were 27%, 13%, and 28%, respectively. Compared to the SARS-CoV-2 vaccination-only group, the risk of systemic symptoms was lower among SIV recipients (OR, 0.2) but comparable among co-vaccinated individuals (OR, 0.8).
Overall, the study findings indicated that influenza co-vaccination, a combination of COVID-19 and influenza vaccines, is an acceptable policy to increase adherence to both vaccines. The findings are in line with previous studies, which found no significant difference in immunogenicity or adverse events compared to SARS-CoV-2 vaccination alone. The study indicates that a single clinic visit can be more effective than two separate visits, especially for vulnerable populations like older people.