Case Fatality Risk of Norovirus in England During a Period of Strain Replacement, 2022/23 - 2024/25 Seasons

Abstract Background Norovirus causes substantial burden to healthcare systems. England experienced high activity in recent seasons alongside a shift in the dominant genotype from GII.4 to GII.17. It remains unclear whether this increased burden reflects changes in severity or other transmission mechanisms associated with the strain replacement. Methods Individual-level testing and mortality data in England from 2022/23-2024/25 seasons were linked from national surveillance systems. Piece-wise exponential additive mixed models estimated all-cause case-fatality risk (CFR) for death within 28 days of a positive test, adjusting for age, location, primary or secondary care case identification and temporal effects. Additional analysis tested the effect of the death linkage threshold. Results CFR did not differ significantly between GII.4 and GII.17, but increased markedly with age and was substantially higher for cases detected in secondary versus primary care. At the 2024/25 season peak, the CFR for the average cohort case (age 75) was 8.01% (95% CI: 6.88–9.33%) for cases identified in secondary care compared with 1.18% (95% CI: 0.61–2.25%) for primary care, likely driven by different case mixes and unmeasured confounding between patients managed in these settings. Interpretation We found no evidence that the newly dominant GII.17 genotype had higher CFR than GII.4 among test-positive cases. The increased burden is therefore more consistent with changes in transmissibility, population immunity, or testing dynamics than increased genotype-specific severity. Norovirus remains a major public health threat, and understanding genotype switching supports enhanced surveillance, expanded genotyping, routine clinical data linkage and advanced modelling to inform control strategies.