细胞激素风暴
瘦素
医学
细胞因子
肥胖
脂肪组织
炎症
免疫学
免疫系统
内科学
细胞因子释放综合征
小鼠苗条素受体
2019年冠状病毒病(COVID-19)
内分泌学
免疫疗法
疾病
嵌合抗原受体
传染病(医学专业)
作者
Tadashi Hosoya,Seiya Oba,Yoji Komiya,Daisuke Kawata,Mamoru Kamiya,Hideyuki Iwai,Shô Miyamoto,Michiyo Kataoka,Minoru Tobiume,Takayuki Kuriyama,Akira Ainai,Hiroyuki Sato,Akihiro Hirakawa,Yuichi Mitsui,Takashi Satoh,Kenji Wakabayashi,Tetsuya Yamada,Yasuhiro Otomo,Yasunari Miyazaki,Hideki Hasegawa,Tadaki Suzuki,Shinsuke Yasuda
标识
DOI:10.1073/pnas.2300155120
摘要
Obesity has been recognized as one of the most significant risk factors for the deterioration and mortality associated with COVID-19, but the significance of obesity itself differs among ethnicity. Multifactored analysis of our single institute-based retrospective cohort revealed that high visceral adipose tissue (VAT) burden, but not other obesity-associated markers, was related to accelerated inflammatory responses and the mortality of Japanese COVID-19 patients. To elucidate the mechanisms how VAT-dominant obesity induces severe inflammation after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, we infected two different strains of obese mice, C57BL/6JHamSlc-ob/ob (ob/ob), C57BLKS/J-db/db (db/db), genetically impaired in the leptin ligand and receptor, respectively, and control C57BL/6 mice with mouse-adapted SARS-CoV-2. Here, we revealed that VAT-dominant ob/ob mice were extremely more vulnerable to SARS-CoV-2 due to excessive inflammatory responses when compared to SAT-dominant db/db mice. In fact, SARS-CoV-2 genome and proteins were more abundant in the lungs of ob/ob mice, engulfed in macrophages, resulting in increased cytokine production including interleukin (IL)-6. Both an anti-IL-6 receptor antibody treatment and the prevention of obesity by leptin replenishment improved the survival of SARS-CoV-2-infected ob/ob mice by reducing the viral protein burden and excessive immune responses. Our results have proposed unique insights and clues on how obesity increases the risk of cytokine storm and death in patients with COVID-19. Moreover, earlier administration of antiinflammatory therapeutics including anti-IL-6R antibody to VAT-dominant patients might improve clinical outcome and stratification of the treatment for COVID-19, at least in Japanese patients.
科研通智能强力驱动
Strongly Powered by AbleSci AI