Non-specific effects of the inactivated influenza vaccine. A test-negative study: The inactivated influenza vaccine and SARS-CoV-2 infections

Anne Jasmijn Sellies; Mirjam J Knol; Hester E de Melker; Patricia C J L Bruijning-Verhagen; Annemarijn R de Boer

doi:10.1016/j.vaccine.2024.04.044

Non-specific effects of the inactivated influenza vaccine. A test-negative study: The inactivated influenza vaccine and SARS-CoV-2 infections

Vaccine. 2024 Apr 23:S0264-410X(24)00468-7. doi: 10.1016/j.vaccine.2024.04.044. Online ahead of print.

Authors

Anne Jasmijn Sellies¹, Mirjam J Knol², Hester E de Melker², Patricia C J L Bruijning-Verhagen³, Annemarijn R de Boer⁴

Affiliations

¹ Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: a.j.sellies@umcutrecht.nl.
² Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
³ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁴ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: a.r.deboer-9@umcutrecht.nl.

PMID: 38658205
DOI: 10.1016/j.vaccine.2024.04.044

Abstract

Background: Previous research suggested that the inactivated influenza vaccine (IIV) may protect against SARS-CoV-2 infection or a severe course of COVID-19. These findings were however based on cohort studies, that are prone to confounding by indication. We examined the association between IIV and SARS-Cov-2 infection in a Dutch population using a test-negative design.

Methods: This test-negative case-control study was conducted in adults (≥60) who tested because of COVID-19 like symptoms at community SARS-CoV-2 testing locations in the Netherlands during the period of November 8th 2021-March 11th 2022. Information on receipt of IIV in October-November 2021 was routinely collected at each visit. Logistic regression was used to calculate unadjusted, partially (sex, age, education level) and fully adjusted (COVID-19 vaccination, IIV 2020) odds ratios (ORs) for receipt of IIV in SARS-CoV-2 positive versus negative subjects. Differential effects on SARS-CoV-2 risk by time since IIV were investigated by including an interaction term for calendar time: November 2021-January 2022 vs February-March 2022.

Results: In total, 1,832 participants were included in the main analysis, of whom 336 (18.3 %) had a positive SARS-CoV-2 test. No significant association between IIV and SARS-CoV-2 infection was found; fully adjusted OR of 1.07 (95 % CI: 0.78-1.49). The interaction term for time periods was not significant (1.04 [95 % CI: 0.51-2.15], p = 0.91). Results were robust in sensitivity analyses.

Conclusions: While earlier observational studies suggested a protective non-specific effect of IIV and SARS-CoV-2 infections, this smaller, but well controlled test-negative design study does not suggest an effect, either positive or negative. Larger test-negative design studies, or alternative designs such as the self-controlled case series design are needed to confirm these findings and provide more definite answers on the topic.

Keywords: Influenza vaccination; Non-specific effects; Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection; Test-negative design.