SARS-CoV-2 Genetic Variants and Patient Factors Associated with Hospitalization Risk

Abstract

ABSTRACTVariants of SARS-CoV-2 have been associated with different transmissibilities and disease severities. The present study examines SARS-CoV-2 genetic variants and their relationship to risk for hospitalization, using data from 12,538 patients from a large, multisite observational cohort study. The association of viral genomic variants and hospitalization is examined with clinical covariates, including COVID-19 vaccination status, outpatient monoclonal antibody treatment status, and underlying risk for poor clinical outcome. Modeling approaches include XGBoost with SHapley Additive exPlanations (SHAP) analysis and generalized linear mixed models. The results indicate that several SARS-CoV-2 lineages are associated with increased hospitalization risk, including B.1.1.7, AY.44, and AY.54. As found in prior studies, Omicron is associated with lower hospitalization risk compared to prior WHO variants. In addition, the results suggest that variants at specific amino acid locations, including locations within Spike protein N-terminal domain and in non-structural protein 14, are associated with hospitalization risk.