Diet-induced obesity and diabetes enhance mortality and reduce vaccine efficacy for SARS-CoV-2

作者：Robert M. Johnson, Jeremy Ardanuy, Holly Hammond, James Logue, Lian Jackson, Lauren Baracco, Marisa E. McGrath, Carly Dillen, Nita Patel, Gale Smith, Matthew B. Frieman · 发表于：Journal of Virology · 年份：2023 · DOI：10.1128/jvi.01336-23 · 被引用次数：18 · 研究领域：COVID-19 Clinical Research Studies、SARS-CoV-2 and COVID-19 Research、Adipokines, Inflammation, and Metabolic Diseases

ABSTRACT Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. As of September 2023, there have been over 770 million confirmed cases of COVID-19, including over 6.9 million deaths. Epidemiologic studies have indicated that comorbidities of obesity and diabetes mellitus are associated with increased morbidity and mortality following SARS-CoV-2 infection. We determined how the comorbidities of obesity and diabetes affect morbidity and mortality following SARS-CoV-2 infection in unvaccinated and adjuvanted spike nanoparticle (NVX-CoV2373) vaccinated mice. We find that obese/diabetic mice infected with SARS-CoV-2 have increased morbidity and mortality compared to age-matched normal mice. Mice that were fed a high-fat diet (HFD) and then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers compared to those fed a normal diet (ND). However, the HFD mice have reduced viral clearance early in infection. Analysis of the inflammatory immune response in HFD mice demonstrates a recruitment of neutrophils that was correlated with increased mortality and reduced clearance of the virus. Depletion of neutrophils in diabetic/obese vaccinated mice reduced disease severity and protected mice from lethality. This model recapitulates the increased disease severity associated with obesity and diabetes in humans with COVID-19 and is an important comorbidity to study...