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

ABSTRACT 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.