Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, 18 October 2023-9 March 2024

Background Assessing variant-specific coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. Methods We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 US states admitted 18 October 2023-9 March 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results A total of 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4580 control patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% confidence interval [CI], 36.1-67.1%) against XBB lineage hospitalization and 32.7% (95% CI, 1.9-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR],. 80; 95% CI,. 46-1.38) and IMV or death (aOR,. 69; 95% CI,. 34-1.40) were not significantly different among JN compared with XBB lineage hospitalizations. Conclusions Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.