Study reveals coadministered COVID-19 and flu vaccines effective, especially in seniors

By Vijay Kumar MalesuReviewed by Benedette Cuffari, M.Sc.Nov 13 2023

In a recent study published in JAMA Network Open, researchers evaluate the effectiveness of coadministering the Pfizer-BioNTech BNT162b2 BA.4/5 bivalent coronavirus disease 2019 (COVID-19) vaccine and seasonal influenza vaccines (SIVs) as compared to administering each vaccine separately in a community setting.

Study: Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine. Image Credit: New Africa / Shutterstock.com

Background 

Due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seasonal surge and declining effectiveness of COVID-19 vaccines over time against new variants, the United States Food and Drug Administration (FDA) recently approved an Omicron-specific booster for the 2023-2024 winter season. Initially, the CDC recommended a 14-day gap between COVID-19 and flu vaccination; however, updated guidelines support simultaneous administration following safety and efficacy studies.

Nevertheless, further research is needed to evaluate the combined effectiveness of coadministered COVID-19 and flu vaccines at the community level.

About the study 

The current study utilized the Optum deidentified Clinformatics Data Mart Database, which comprises a diverse population from U.S. commercial and Medicare Advantage health plans, to assess the effectiveness of coadministering BNT162b2-biv and SIVs. The study included adults over the age of 18 who were enrolled in insurance plans by August 2022 and received either of the vaccines or both between August 2022 and January 2023.

Exclusions applied to individuals with prior COVID-19 or influenza diagnosis, those who received a different COVID-19 vaccine, or those who received a second vaccine dose too soon after the first.

The researchers compared the same-day coadministration of BNT162b2-biv and SIV with their separate administration, specifically considering only enhanced SIVs for participants over 65 years of age. Vaccination statuses were identified through diverse coding systems across various healthcare settings.

Key outcomes of the study included hospitalizations, emergency department visits, and outpatient appointments, in which specific International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes were used.

The study evaluated relative risks for COVID-19 and influenza outcomes by comparing groups who were coadministered vaccines with those who received these vaccines individually. Negative control outcomes included urinary tract infections and unintentional injuries to detect biases.

The researchers thoroughly examined variables, including demographics, clinical profiles, vaccination records, and health-seeking behaviors. Using logistic regression models, propensity scores and stabilized inverse probability of treatment weights (IPTWs) were generated to balance baseline characteristics. Hazard ratios for different outcomes were determined through Cox proportional hazards regression models.

A sensitivity analysis was conducted to address the effects of specific COVID-19 and influenza treatments. The research, categorized by age groups, refrained from formal statistical significance testing, relying instead on SAS and R for data analysis. The follow-up phase of the study began 15 days after vaccination and continued until predefined endpoints were reached.

Study results 

In a study using the Optum deidentified Clinformatics Data Mart Database, 3,442,996 individuals met the criteria for analysis, with a mean age of 65 years. Among those aged 65 and older, 17.3% received both vaccines, with a higher percentage of women and many having a Charlson Comorbidity Index score of two or higher. The BNT162b2-biv vaccine was predominantly administered in retail pharmacies, whereas SIV administration was more evenly divided between offices and pharmacies.

In those between 18 and 64 years of age, the prevalent SIVs were egg- and cell-based standard-dose types. The application of IPTWs achieved a balance in covariates, although discrepancies remained in the geographic region and the month of the index date. The median follow-up duration varied among the groups, with the longest being 109 days for older participants receiving coadministered vaccines.

Upon examining COVID-19-related outcomes, all groups exhibited generally low incidence rates. Notably, those in the coadministration group experienced similar or marginally increased rates of COVID-19 outcomes as compared to those receiving only a single vaccine at once.

The assessment of negative control outcomes revealed minimal bias. By calibrating the results with these outcomes, the risk estimates were adjusted closer to neutral, thus enhancing the reliability of the findings.

Regarding influenza-related outcomes, the coadministration group, particularly those 65 years of age and older, was associated with a lower incidence of all influenza-related outcomes as compared to the SIV-only group. This pattern was consistent in the younger age group, with most confidence intervals crossing 1.00 after calibration with negative control outcomes.

Sensitivity analyses, which included censoring for COVID-19 or influenza treatment and requiring a primary position diagnosis code for hospitalization, showed similar results across all outcomes and age groups.