Impact of accounting for correlation between COVID-19 and influenza vaccination in a COVID-19 vaccine effectiveness evaluation using a test-negative design

Vaccine. 2023 Dec 12;41(51):7581-7586. doi: 10.1016/j.vaccine.2023.11.025. Epub 2023 Nov 23.


Test-negative-design COVID-19 vaccine effectiveness (VE) studies use symptomatic SARS-CoV-2-positive individuals as cases and symptomatic SARS-CoV-2-negative individuals as controls to evaluate COVID-19 VE. To evaluate the potential bias introduced by the correlation of COVID-19 and influenza vaccination behaviors, we assessed changes in estimates of VE of bivalent vaccines against COVID-19-associated hospitalizations and emergency department/urgent care (ED/UC) encounters when considering influenza vaccination status or including or excluding influenza-positive controls using data from the multi-state VISION vaccine effectiveness network. Analyses included encounters during October 2022 - February 2023, a period of SARS-CoV-2 and influenza cocirculation. When considering influenza vaccination status or including or excluding influenza-positive controls, COVID-19 VE estimates were robust, with most VE estimates against COVID-19-associated hospitalization and ED/UC encounters changing less than 5 percentage points. Higher proportions of influenza-positive patients among controls, influenza vaccination coverage, or VE could impact these findings; the potential bias should continue to be assessed.

Keywords: COVID-19; Influenza; Negative; SARS-CoV-2; Test; Vaccine effectiveness.

MeSH terms

  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • SARS-CoV-2
  • Vaccination
  • Vaccine Efficacy


  • COVID-19 Vaccines
  • Influenza Vaccines