XBB.1.5 mRNA COVID-19 Vaccination and Inpatient or Emergency Department Visits Among Adults Infected with SARS-CoV-2 JN.1 and XBB-Lineage Variants

Within a multi-state viral genomic surveillance program, we conducted a case-control analysis comparing prior receipt of XBB.1.5-adapted mRNA vaccination between SARS-CoV-2-infected adults with inpatient/ED visits (proxy for severe illness) vs outpatient visits. Among 6,551 patients from September 2023-January 2024, 6.1% with inpatient/ED visits vs 12.0% with outpatient visits had received XBB.1.5 vaccination (aOR=0.41; 95%CI:0.32-0.53). This protective association was weaker among JN.1 (aOR=0.62; 95%CI:0.40-0.96) vs XBB-lineage (aOR=0.28; 95%CI:0.18-0.43) variant infections (interaction, p=0.003). XBB.1.5 vaccination was also protective specifically compared to BA.4/BA.5-adapted mRNA vaccination (aOR=0.60; 95%CI:0.45-0.79). XBB.1.5 vaccines protect against severe illness, but protection may be weaker against JN.1 vs XBB-lineage variants. ### Competing Interest Statement MEL, VC, LMM, ETC, DW, ADR, HD, MI, NLW, TB, KT, JN, JR, ES, WL, JL, and SL are employees of Helix, Inc. MEL, MI, and SL report contracted research from Pfizer. MEL, MI, WL, and SL report contracted research from the Centers for Disease Control and Prevention (CDC). MEL reports contracted research and travel support from Novavax. PRH reports contracted research from Seegene USA and Helix, Inc. JDG reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron; grants from Merck (BARDA) and Gilead; speaking honoraria and personal fees from Gilead Sciences, Inc, and Eli Lilly & Co; and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and LabCorp; and serving as a speaker or advisory board member for Gilead and Eli Lilly. CAS reports giving educational lectures sponsored by Eli Lilly. DM, RED, and WBG report no potential conflicts. ### Funding Statement This study was funded by Helix. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Protocols were reviewed and approved by the WIRB CG IRB (Western Institutional Review Board, WIRB-Copernicus Group; approval number 20224919) and the Medical University of South Carolina (MUSC) Institutional Review Board for Human Research (approval number Pro00129083). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data collected for this study are not available. Data sharing agreements between Helix and partner institutions prohibit Helix from making this dataset publicly available.