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Vaccine . A systematic meta-analytic comparative evaluation of seasonal influenza vaccine effectiveness from test-negative design studies in the No

tetano

Editor, Senior Moderator
Vaccine


. 2026 Jul 22:88:128956.
doi: 10.1016/j.vaccine.2026.128956. Online ahead of print.
A systematic meta-analytic comparative evaluation of seasonal influenza vaccine effectiveness from test-negative design studies in the Northern Hemisphere pre/post COVID-19 pandemic

George N Okoli[SUP] 1 [/SUP], Sheena G Sullivan[SUP] 2 [/SUP], Diane M Harper[SUP] 3 [/SUP], Tim K Tsang[SUP] 4 [/SUP], Benjamin J Cowling[SUP] 5 [/SUP]


Affiliations
Abstract

Background: Influenza circulation was substantially reduced during the COVID-19 pandemic. The consequent reduction in population immunity may have resulted in increased influenza vaccine effectiveness (VE) after the pandemic via reduced immunity in unvaccinated individuals compared to the pre-pandemic period.
Methods: We systematically reviewed published peer-reviewed test-negative design (TND) studies of seasonal influenza VE against medically-attended, laboratory-confirmed influenza in the Northern Hemisphere. We compared pooled VE estimates before (2010/11-2019/20) and after (2022/23-2024/25) the COVID-19 pandemic (defined as 2020/21-2021/22). Pooled VE against A(H1N1)pdm09, A(H3N2), influenza B, and B/Victoria was calculated for three age groups (6 months-17 years, 18-64 years, ≥65 years) using inverse-variance random-effects meta-analysis. Heterogeneity was quantified with the I[SUP]2[/SUP] statistic, and differences between pooled VE estimates pre- and post-pandemic periods were tested with the χ[SUP]2[/SUP] statistic.
Results: Eighty-five publications were included. Post-pandemic VE against A(H3N2) was significantly higher than pre-pandemic VE in 6-month-17-year-olds (53% [42-64%] vs 37% [30-45%]) and 18-64-year-olds (35% [25-45%] vs 21% [13-29%]). Similarly, VE against influenza B was higher post-pandemic in both age groups (85% [78-93%] vs 52% [45-60%] and 73% [59-87%] vs 49% [41-57%], respectively). Conversely, VE against A(H1N1)pdm09 was lower post-pandemic in 18-64-year-olds (37% [27-46%] vs 55% [47-62%]). No significant differences were observed for ≥65-year-olds, and data for B/Victoria were limited.
Conclusions: The evidence suggests slightly higher VE against seasonal influenza after the COVID-19 pandemic although there may be factors other than population immunity that may explain our observations.

Keywords: Influenza; Meta-analysis; Population immunity; Vaccination effectiveness.

 
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