Impaired inflammatory resolution with severe SARS-CoV-2 infection in leptin knock out obese hamster.

ABSTRACT: Comorbidities, such as obesity, increase the risk of severe COVID-19. However, the mechanisms underlying severe illnesses in individuals with obesity are poorly understood. Here, we used gene-edited leptin knock out (Leptin ^-/-) obese hamsters to establish a severe infection model. This model exhibits robust viral replication, severe lung lesions, pronounced clinical symptoms, and fatal infection, mirroring severe COVID-19 in patients with obesity. Using single-cell transcriptomics on lung tissues pre- and post-infection, we found that monocyte-derived alveolar macrophages (MD-AM) play a key role in lung hyper-inflammation, including two unique MD-AM cell fate branches specific to Leptin ^-/- hamsters. Notably, reduced Trem2-dependent efferocytosis pathwa

SUBMITTER: Jiang RD 

PROVIDER: S-EPMC11841202 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature