BACKGROUND: The epidemiology of respiratory viruses and vaccine effectiveness (VE) in the community is not well described. This study assessed VE against a positive test of influenza (VEf) and SARS-CoV-2 (VECov). METHODS: Data from two large networks of community-based laboratories in France were collected during standard of care in the 2023-2024 epidemic season (n = 511,083 RT-PCR tests). Multiplex PCR diagnostic tests were used. Patients' demographics and symptoms were reported in addition to viral sequencing results. Test-negative design was used to separately estimate VEf and VECov, overall and stratified, by time since vaccination and calendar week. RESULTS: Adjusted VEf by age-group, sex, presence of symptoms, PCR technique, and week of testing, was 47.6% (95% CI: 44.3%-50.7%). VEf was lower in patients ≥65 years (42.0%
95% CI: 36.6%-46.9%) than 18-64 years (52.9%
95% CI: 48.6%-56.8%). The adjusted VEf against type A influenza, that represented 98% of typed viruses, was 51% (95% CI: 45%-56.6%) for patients vaccinated 15 days to 3 months before testing, and 35.5% (95% CI: 24.2%-45.3%) for those vaccinated 3 to 6 months before testing. For VECov, the adjusted estimate in patients vaccinated 15 days to 3 months prior to testing were 40.6% (95% CI: 7.2%-58.6%) at week 39, 24.8% (95% CI: 4.0%-38.8%) at week 45, and dropped systematically through the epidemic season as the JN.1 variant became dominant. CONCLUSION: This study showed moderate VEf and VECov against infection in the community and highlighted the impact of time since vaccination and age for both estimates, and the new variant emergence on VECov. These findings should be considered in future vaccination campaigns.