Obesity Alters the Metabolic and Immunologic Response of Pulmonary T Cells to SARS-CoV-2 Infection 2143

Abstract Description Obesity is a significant risk factor for worse clinical outcomes in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Although obesity is known to alter immune function, the mechanisms by which it affects local and systemic SARS-CoV-2 immunity and worsens disease severity remain unclear. Here, we compared virus–host dynamics in genetically obese Lepob (ob/ob) mice and lean control mice after intranasal infection with SARS-CoV-2 Beta (B.1.351). Obese mice exhibited delayed viral clearance from the lungs, worse histopathologic pulmonary injury, and worse clinical outcomes compared with infected lean mice. Pulmonary CD8+ T cells in obese mice displayed an exaggerated SARS-CoV-2-specific cytokine response and a marked shift in energy metabolism towards preferential fatty acid utilization. SARS-CoV-2 clearance from the lungs of obese mice was normalized by adoptive transfer of CD8+ T cells from SARS-CoV-2-immune lean mice. Collectively, these data suggest that obesity is associated with cell-autonomous metabolic and immunologic abnormalities in pulmonary SARS-CoV-2-specific CD8+ T cells that contribute to delayed viral clearance and worse clinical outcomes in infected obese mice. Funding Sources This study was funded by National Institutes of Health grants U19 AI142790-02S1 (to SS and EOS), the GHR Foundation (to SS and EOS), the Arvin Gottleib Foundation (to SS), and the Overton family (to SS and EOS). This research was also supported by a La Jolla Institute for Immunology (LJI) /Kyowa Kirin Inc. (KKNA) Interactive Fund. Topic Categories Viral Immunology (VIR)