Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine
Authors: McGrath Leah J. , Malhotra Deepa , Miles Amanda C. , Welch Verna L. , Di Fusco Manuela , Surinach Andy , Barthel Andrea , Alfred Tamuno , Jodar Luis , McLaughlin John M. 
Published: November 2023

ImportanceNo data comparing the estimated effectiveness of coadministering COVID-19 vaccines with seasonal influenza vaccine (SIV) in the community setting exist.ObjectiveTo examine the comparative effectiveness associated with coadministering the BNT162b2 BA.4/5 bivalent mRNA COVID-19 vaccine (BNT162b2-biv [Pfizer BioNTech]) and SIV vs giving each vaccine alone.Design, Setting, and ParticipantsA retrospective comparative effectiveness study evaluated US adults aged 18 years or older enrolled in commercial health insurance or Medicare Advantage plans and vaccinated with BNT162b2-biv only, SIV only, or both on the same day between August 31, 2022, and January 30, 2023. Individuals with monovalent or another brand of mRNA bivalent COVID-19 vaccine were excluded.ExposureSame-day coadministration of BNT162b2-biv and SIV; receipt of BNT162b2-biv only (for COVID-19–related outcomes) or SIV only (for influenza-related outcomes) were the comparator groups. For adults aged 65 years or older, only enhanced SIVs were included.Main Outcomes and MeasuresCOVID-19–related and influenza-related hospitalization, emergency department (ED) or urgent care (UC) encounters, and outpatient visits.ResultsOverall, 3 442 996 individuals (57.0% female; mean [SD] age, 65 [16.7] years) were included. A total of 627 735 individuals had BNT162b2-biv and SIV vaccine coadministered, 369 423 had BNT162b2-biv alone, and 2 445 838 had SIV alone. Among those aged 65 years or older (n = 2 210 493; mean [SD] age, 75 [6.7] years; 57.9% female), the coadministration group had a similar incidence of COVID-19–related hospitalization (adjusted hazard ratio [AHR], 1.04; 95% CI, 0.87-1.24) and slightly higher incidence of emergency department or urgent care encounters (AHR, 1.12; 95% CI, 1.02-1.23) and outpatient visits (AHR, 1.06; 95% CI, 1.01-1.11) compared with the BNT162b2-biv–only group. Among individuals aged 18 to 64 years (n = 1 232 503; mean [SD] age, 47 [13.1] years; 55.4% female), the incidence of COVID-19–related outcomes was slightly higher among those who received both vaccines vs BNT162b2-biv alone (AHR point estimate range, 1.14-1.57); however, fewer events overall in this age group resulted in wider CIs. Overall, compared with those who received SIV alone, the coadministration group had a slightly lower incidence of most influenza-related end points (AHR point estimates 0.83-0.93 for those aged ≥65 years vs 0.76-1.08 for those aged 18-64 years). Negative control outcomes suggested residual bias and calibration of COVID-19–related and influenza-related outcomes with negative controls moved all estimates closer to the null, with most CIs crossing 1.00.Conclusions and RelevanceIn this study, coadministration of BNT162b2-biv and SIV was associated with generally similar effectiveness in the community setting against COVID-19–related and SIV-related outcomes compared with giving each vaccine alone and may help improve uptake of both vaccines.