饮食诱导的肥胖和糖尿病会增加死亡率并降低针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的疫苗效力。

Diet Induced Obesity and Diabetes Enhance Mortality and Reduces Vaccine Efficacy for SARS-CoV-2.

作者信息

Johnson Robert, Ardunay Jeremy, Hammond Holly, Logue James, Jackson Lian, Baracco Lauren, McGrath Marisa, Dillen Carly, Patel Nita, Smith Gale, Frieman Matthew

出版信息

bioRxiv. 2023 May 5:2022.10.15.512291. doi: 10.1101/2022.10.15.512291.

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 October 2022, there have been over 625 million confirmed cases of COVID-19, including over 6.5 million deaths. Epidemiological 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 fed a high-fat diet (HFD) then vaccinated with NVX-CoV2373 produce equivalent neutralizing antibody titers 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 with increasing obesity and diabetes across the world.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是2019冠状病毒病(COVID-19)的病原体,于2019年12月在中国武汉出现。截至2022年10月,COVID-19确诊病例已超过6.25亿例,其中死亡病例超过650万例。流行病学研究表明,肥胖和糖尿病合并症与SARS-CoV-2感染后的发病率和死亡率增加有关。我们确定了肥胖和糖尿病合并症如何影响未接种疫苗和接种了佐剂刺突纳米颗粒(NVX-CoV2373)的小鼠在感染SARS-CoV-2后的发病率和死亡率。我们发现,与年龄匹配的正常小鼠相比,感染SARS-CoV-2的肥胖/糖尿病小鼠发病率和死亡率更高。喂食高脂饮食(HFD)然后接种NVX-CoV2373的小鼠产生的中和抗体滴度与喂食正常饮食(ND)的小鼠相当。然而,HFD小鼠在感染早期的病毒清除率降低。对HFD小鼠炎症免疫反应的分析表明,中性粒细胞的募集与死亡率增加和病毒清除率降低相关。在糖尿病/肥胖接种疫苗的小鼠中消耗中性粒细胞可降低疾病严重程度并保护小鼠免于死亡。该模型概括了COVID-19患者中与肥胖和糖尿病相关的疾病严重程度增加,并且是随着全球肥胖和糖尿病发病率增加而需要研究的重要合并症。

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