Namkoong, Ho

写真a

Affiliation

School of Medicine, Department of Infectious Diseases （Shinanomachi）

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

E-mail Address

E-mail address

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Papers 【 Display / hide 】

  • Impact of respiratory bacterial infections on mortality in Japanese patients with COVID-19: a retrospective cohort study.

    Kensuke Nakagawara, Hirofumi Kamata, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Shiro Otake, Takahiro Fukushima, Tatsuya Kusumoto, Atsuho Morita, Shuhei Azekawa, Mayuko Watase, Takanori Asakura, Katsunori Masaki, Makoto Ishii, Akifumi Endo, Ryuji Koike, Hiroyasu Ishikura, Tohru Takata, Yasushi Matsushita, Norihiro Harada, Hiroyuki Kokutou, Takashi Yoshiyama, Kensuke Kataoka, Yoshikazu Mutoh, Masayoshi Miyawaki, Soichiro Ueda, Hiroshi Ono, Takuya Ono, Tomohisa Shoko, Hiroyuki Muranaka, Kodai Kawamura, Nobuaki Mori, Takao Mochimaru, Mototaka Fukui, Yusuke Chihara, Yoji Nagasaki, Masaki Okamoto, Masaru Amishima, Toshio Odani, Mayuko Tani, Koichi Nishi, Yuya Shirai, Ryuya Edahiro, Akira Ando, Naozumi Hashimoto, Shinji Ogura, Yuichiro Kitagawa, Toshiyuki Kita, Takashi Kagaya, Yasuhiro Kimura, Naoki Miyazawa, Tomoya Tsuchida, Shigeki Fujitani, Koji Murakami, Hirohito Sano, Yuki Sato, Yoshinori Tanino, Ryo Otsuki, Shuko Mashimo, Mizuki Kuramochi, Yasuo Hosoda, Yoshinori Hasegawa, Tetsuya Ueda, Yotaro Takaku, Takashi Ishiguro, Akiko Fujiwara, Naota Kuwahara, Hideya Kitamura, Eri Hagiwara, Yasushi Nakamori, Fukuki Saito, Yuta Kono, Shinji Abe, Tomoo Ishii, Takehiko Ohba, Yu Kusaka, Hiroko Watanabe, Makoto Masuda, Hiroki Watanabe, Yoshifumi Kimizuka, Akihiko Kawana, Yu Kasamatsu, Satoru Hashimoto, Yukinori Okada, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Katsushi Tokunaga, Seiya Imoto, Yuko Kitagawa, Akinori Kimura, Satoru Miyano, Naoki Hasegawa, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

    BMC pulmonary medicine 23 （ 1 ） 146 - 146 2023.04

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    BACKGROUND: Although cases of respiratory bacterial infections associated with coronavirus disease 2019 (COVID-19) have often been reported, their impact on the clinical course remains unclear. Herein, we evaluated and analyzed the complication rates of bacterial infections, causative organisms, patient backgrounds, and clinical outcome in Japanese patients with COVID-19. METHODS: We performed a retrospective cohort study that included inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021) and obtained demographic, epidemiological, and microbiological results and the clinical course and analyzed the cases of COVID-19 complicated by respiratory bacterial infections. RESULTS: Of the 1,863 patients with COVID-19 included in the analysis, 140 (7.5%) had respiratory bacterial infections. Community-acquired co-infection at COVID-19 diagnosis was uncommon (55/1,863, 3.0%) and was mainly caused by Staphylococcus aureus, Klebsiella pneumoniae and Streptococcus pneumoniae. Hospital-acquired bacterial secondary infections, mostly caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were diagnosed in 86 patients (4.6%). Severity-associated comorbidities were frequently observed in hospital-acquired secondary infection cases, including hypertension, diabetes, and chronic kidney disease. The study results suggest that the neutrophil-lymphocyte ratio (> 5.28) may be useful in diagnosing complications of respiratory bacterial infections. COVID-19 patients with community-acquired or hospital-acquired secondary infections had significantly increased mortality. CONCLUSIONS: Respiratory bacterial co-infections and secondary infections are uncommon in patients with COVID-19 but may worsen outcomes. Assessment of bacterial complications is important in hospitalized patients with COVID-19, and the study findings are meaningful for the appropriate use of antimicrobial agents and management strategies.

  • Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity.

    Ryuya Edahiro, Yuya Shirai, Yusuke Takeshima, Shuhei Sakakibara, Yuta Yamaguchi, Teruaki Murakami, Takayoshi Morita, Yasuhiro Kato, Yu-Chen Liu, Daisuke Motooka, Yoko Naito, Ayako Takuwa, Fuminori Sugihara, Kentaro Tanaka, James B Wing, Kyuto Sonehara, Yoshihiko Tomofuji, Ho Namkoong, Hiromu Tanaka, Ho Lee, Koichi Fukunaga, Haruhiko Hirata, Yoshito Takeda, Daisuke Okuzaki, Atsushi Kumanogoh, Yukinori Okada

    Nature genetics  2023.04

    ISSN  1061-4036

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    Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell-cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

  • Characteristics and Clinical Effectiveness of COVID-19 Vaccination in Hospitalized Patients in Omicron-dominated Epidemic Wave - A Nationwide Study in Japan.

    Hiromu Tanaka, Shotaro Chubachi, Takanori Asakura, Ho Namkoong, Shuhei Azekawa, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Ho Lee, Mayuko Watase, Kaori Sakurai, Tatsuya Kusumoto, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 132   84 - 88 2023.04

    ISSN  1201-9712

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    OBJECTIVES: Coronavirus disease (COVID-19) was severe in the Delta variant-dominated epidemic wave (fifth wave) in Japan. The clinical characteristics and effectiveness of COVID-19 vaccination are not fully understood in the Omicron variant-dominated wave (sixth and seventh waves), especially in hospitalized patients. We investigated the relationship between vaccination and disease severity in the Omicron-dominated wave and compared these variant-dominated waves. METHODS: The nationwide COVID-19 database (Japan COVID-19 Task Force) was used to compare clinical characteristics and critical outcome in patients hospitalized from Delta (5th, N=735) vs Omicron-dominated waves (6th, N=495; 7th, N=128). RESULTS: Patients in the sixth and seventh waves had a lower incidence of critical outcomes and respiratory outcomes, and a higher incidence of bacterial infection, although the mortality rate did not differ significantly between waves. In the sixth and seventh waves, 138 (27.9%) and 29 (22.7%) COVID-19 patients were unvaccinated, respectively. Multivariable analysis adjusted with previously reported factors revealed that the proportion of 1) critical outcomes and 2) respiratory outcomes decreased in a frequency-dependent manner; 1) (the number of vaccinations): 1-2 times, aOR 0.37 (95% CI; 0.20-0.69); 3-4 times: aOR 0.25 (95% CI; 0.11-0.58), 2) 1-2 times, aOR 0.43 (95% CI; 0.27-0.66); 3-4 times: aOR 0.36 (95% CI; 0.21-0.60). CONCLUSIONS: COVID-19 hospitalized patients with Omicron infections showed a lower incidence of critical outcomes than those with Delta infections, and COVID-19 vaccination may contribute to preventing respiratory failure.

  • Use of the neutrophil-to-lymphocyte ratio and an oxygen requirement to predict disease severity in patients with COVID-19.

    Takuya Ozawa, Takanori Asakura, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ko Lee, Takahiro Fukushima, Shiro Otake, Kensuke Nakagawara, Mayuko Watase, Katsunori Masaki, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Koji Murakami, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

    Respiratory investigation 61 （ 4 ） 454 - 459 2023.04

    ISSN  2212-5345

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    We investigated the association between complete blood count, including neutrophil-to-lymphocyte ratio (NLR) in combination with patient characteristics, and coronavirus disease (COVID-19) outcomes to identify the best prognostic indicator. We analyzed data of patients with confirmed COVID-19 from the nationwide database of the Japan COVID-19 Task Force between February 2020 and November 2021. A composite outcome was defined as the most severe condition, including noninvasive positive-pressure ventilation, high-flow nasal cannula, invasive mechanical ventilation, extracorporeal membrane oxygenation, or death. Of 2425 patients in the analysis, 472 (19.5%) experienced a composite outcome. NLR was the best predictor of composite outcomes, with an area under the curve (AUC) of 0.81, and a sensitivity and specificity of 72.3% and 75.7%, respectively, using a cut-off value of 5.04. The combination of NLR and an oxygen requirement on admission had the highest AUC (0.88). This simple combination may help identify patients at risk of progression to severe disease.

  • 特集 ポストコロナ時代の感染症診療 第II章　感染症診療各論 [4]呼吸器感染症 6　肺非結核性抗酸菌症

    加治 正憲, 南宮 湖, 長谷川 直樹

    診断と治療 （診断と治療社)  111 （ 13 ） 121 - 125 2023.03

    ISSN  0370999X

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明

    南宮 湖, 福永 興壱

    臨床免疫・アレルギー科 ((有)科学評論社)  79 ( 3 ) 332 - 338 2023.03

    ISSN  1881-1930

  • 【COVID-19重症化・後遺症のメカニズム　免疫応答の個人差がみえてきた】COVID-19重症化の遺伝的背景

    南宮 湖, 福永 興壱

    実験医学 ((株)羊土社)  41 ( 4 ) 509 - 514 2023.03

    ISSN  0288-5514

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    新型コロナウイルス感染症(COVID-19)は無症候性感染から重症例・死亡例に至るまでさまざまな臨床経過をたどる.この要因として,病原体側の因子以外に宿主因子が注目され,世界中で研究が進められている.I型IFNに対する中和自己抗体やCOVID-19 Host Genetics InitiativeによるメタGWASによる疾患感受性遺伝子の同定が報告されてきた.日本においても100以上の病院が参加したコロナ制圧タスクフォースによりGWASが実施され,DOCK2を同定した.さらに,DOCK2はCOVID-19の重症化のマーカーとなるだけでなく,COVID-19の治療標的となることが見出された.(著者抄録)

  • 肺MAC症の病型に関連する細菌側因子のGWASによる探索

    矢野 大和, 有川 健太郎, 西内 由紀子, 三澤 可奈, 西村 知泰, 大田 篤, 丸山 史人, 三木 真理, 阿戸 学, 長谷川 直樹, 木田 博, 南宮 湖, 北田 清悟, 岩本 朋忠

    日本細菌学雑誌 (日本細菌学会)  78 ( 1 ) 82 - 82 2023.02

    ISSN  0021-4930

  • 【Priority Pathogen List(PPL)に取り上げられる耐性菌】非結核性抗酸菌

    森田 篤帆, 南宮 湖, 長谷川 直樹

    臨床と微生物 ((株)近代出版)  50 ( 1 ) 067 - 073 2023.01

    ISSN  0910-7029

    　View Summary

    非結核性抗酸菌は日本版PPL(第1版)のPriority1に位置付けられた.これは罹患者数が増加傾向で死亡例も多いこと,薬剤耐性や副作用により治療に難渋することが背景にある.克服に向けてさらなる治療選択肢の拡大が望まれる.(著者抄録)

  • 尿酸とCOVID-19　コロナ制圧タスクフォースによる日本人COVID-19重症化宿主因子の同定の試み　日本人COVID-19集団における尿酸の役割

    南宮 湖

    日本痛風・尿酸核酸学会総会プログラム・抄録集 ((一社)日本痛風・尿酸核酸学会)  56回   66 - 66 2023.01

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 肺非結核性抗酸菌症患者の宿主疾患感受遺伝子の機能解析による新規治療基盤の創出

    2023.04
    -
    2026.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), No Setting

  • Elucidation of pathogenesis of pulmonary diseases due to nontuberculous mycobacteria using the human lungs

    2022.04
    -
    2025.03

    Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), No Setting

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    非結核性抗酸菌(NTM; nontuberculous mycobacteria)は環境に存在する弱毒菌で、主に中高年以降の女性や既に肺疾患を有する患者に好発する難治性の慢性進行性呼吸器感染症である。抗菌薬治療における効果は限られ治癒が困難であること、新規抗菌薬開発が危機的状態にあることから新たな治療戦略が求められる。本研究では肺NTM症の末梢気道病変に着目し、肺組織検体を用いて詳細な分子生物学的解析を施行し、他の実験系（細胞培養、マウス）・患者由来の臨床検体、情報と共に解析することで、新たな治療標的を創出することを目的とする。

  • ムチン異常集積に着目した肺非結核性抗酸菌症の病態解明

    2021.10
    -
    2024.03

    Grants-in-Aid for Scientific Research, Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)), No Setting

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    肺非結核性抗酸菌(NTM)症は慢性進行性呼吸器感染症で、日本における罹患率は近年増加し世界の中でも最も高い国のうちの一つである。抗菌薬治療における効果は限られ、新たな治療戦略が求められる。申請者は肺NTM症に特徴的な気管支拡張病変において、気道における粘液線毛クリアランス(MCC)の粘液層を構成するムチン蛋白が末梢気道で異常集積していることに着目した。本研究では本邦で集積した肺NTM症の喀痰検体を使用し、ノースカロライナ大学との国際共同研究により、肺NTM症におけるムチンの異常を明らかにすることを目的とする。
    肺非結核性抗酸菌(NTM)症は難治性の慢性進行性呼吸器感染症であり、抗菌薬治療における効果は限られ、新たな治療戦略が求められる。申請者のグループは、肺NTM症の患者情報・臨床検体を含むデータベースを構築し、解析・報告する中で、同疾患に特徴的な気管支拡張病変に着目した。本研究では、申請者らが集積した喀痰などの臨床検体を用いて、 国際共同研究先あるノースカロライナ大学(UNC)が独自に有する系により、ムチンおよび生物物理学的特徴を解析する。申請者は肺NTM症・気管支拡張症の病理検体を用いて、主座が末梢気道病変にあり、ムチン異常集積が重要であることを明らかにした(In preparation)。慶應義塾大学病院で倫理委員会で承認を得て集積した検体は200例以上となり、その一部をノースカロライナ大学に搬送し、解析のための検体準備を進めた。また同時に、患者における臨床情報を集積し、さらなる分子生物学的解析を施行するための病理組織および気道上皮細胞を集積している。
    臨床検体・情報に関しては順調に集められているものの、新型コロナウイルスの影響もあり、共同研究先の装置の故障・修理に時間を要したため、サンプルの解析が限られた。
    新型コロナウイルスの影響があり、渡航は中々困難な状況ではあるが連絡を密に取ることで対応している。今後も研究実施計画に沿って研究を進めていく予定である。研究物品の調達が困難な場合にはその都度計画を変更し、米国・日本のそれぞれに合わせた最適な実験環境で薦めていく。

  • Elucidation of host susceptibility to pulmonary NTM disease and bronchiectasis

    2021.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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    公衆衛生上重要な感染症であることが近年判明してきた肺NTM症は疾患感受性遺伝子の存在が指摘されていた。研究代表者は肺MAC症の発症に関連する遺伝的変異を探索するために、1066名の肺MAC症患者コホートと対照群について世界ではじめて本疾患のゲノムワイド関連解析を実施し、CHP2領域に存在するrs109592が強く発症リスクと関連することを示しました。さらに、国際共同研究により日本人集団のみならず、韓国人集団・ヨーロッパ人集団においても関連していることを示した。本研究では、コホートを更に拡大させ、肺NTM症の疾患感受性遺伝子を探索すると共に、CHP2の機能解析を目指す。

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Courses Taught 【 Display / hide 】

  • PRINCIPLES OF HEALTH MANAGEMENT

    2024

  • INFECTIOUS DISEASES

    2024

  • ADVANCED HUMAN BODY AND PHYSIOLOGY

    2024

  • INTEGRATION OF BASIC SCIENCE AND CLINICAL MEDICINE

    2023

  • INFECTIOUS DISEASES

    2023

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