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Apple-shaped obesity: A risky soil for cytokine-accelerated severity in COVID-19.
Hosoya, Tadashi; Oba, Seiya; Komiya, Yoji; Kawata, Daisuke; Kamiya, Mari; Iwai, Hideyuki; Miyamoto, Sho; Kataoka, Michiyo; Tobiume, Minoru; Kanno, Takayuki; Ainai, Akira; Sato, Hiroyuki; Hirakawa, Akihiro; Mitsui, Yuichi; Satoh, Takashi; Wakabayashi, Kenji; Yamada, Tetsuya; Otomo, Yasuhiro; Miyazaki, Yasunari; Hasegawa, Hideki; Suzuki, Tadaki; Yasuda, Shinsuke.
  • Hosoya T; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Oba S; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Komiya Y; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Kawata D; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Kamiya M; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Iwai H; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Miyamoto S; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Kataoka M; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Tobiume M; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Kanno T; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Ainai A; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Sato H; Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Hirakawa A; Department of Clinical Biostatistics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Mitsui Y; Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Satoh T; Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Wakabayashi K; Department of Intensive Care Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Yamada T; Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Otomo Y; Trauma and Acute Critical Care Medical Center, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Miyazaki Y; Department of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
  • Hasegawa H; Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Suzuki T; Department of Pathology, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
  • Yasuda S; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Proc Natl Acad Sci U S A ; 120(22): e2300155120, 2023 05 30.
Article in English | MEDLINE | ID: covidwho-2323651
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Malus / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Long Covid Limits: Animals Language: English Journal: Proc Natl Acad Sci U S A Year: 2023 Document Type: Article Affiliation country: Pnas.2300155120

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Malus / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Long Covid Limits: Animals Language: English Journal: Proc Natl Acad Sci U S A Year: 2023 Document Type: Article Affiliation country: Pnas.2300155120