Diabetes exacerbates SARS-CoV-2 replication through ineffective pulmonary interferon responses, delayed cell-mediated immunity, and disruption of leptin signaling.

ABSTRACT: Comorbidities, including obesity and type 2 diabetes mellitus (T2DM), are associated with increased disease severity and mortality following SARS-CoV-2 infection. Here, we investigated virus-host interactions under the effects of these comorbidities in diet-induced obesity (DIO) and leptin receptor-deficient (T2DM) mice following infection with SARS-CoV-2. DIO mice, as well as their lean counterparts, showed limited susceptibility to SARS-CoV-2 infection. In contrast, T2DM mice showed exacerbated pulmonary SARS-CoV-2 replication and delayed viral clearance associated with down-regulation of innate and adaptative immune gene signatures, ineffective type I interferon response, and delayed SARS-CoV-2-specific cell-mediated immune responses. While T2DM mice showed higher and prolonged SARS-CoV

SUBMITTER: Thieulent CJ 

PROVIDER: S-EPMC11925909 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature