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Papers - Namkoong, Ho

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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

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.

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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

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.

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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

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.

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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

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.

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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

Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination

Yoshifumi Uwamino, Kengo Nagashima, Ayumi Yoshifuji, Shigeru Suga, Mizuho Nagao, Takao Fujisawa, Munekazu Ryuzaki, Yoshiaki Takemoto, Ho Namkoong, Masatoshi Wakui, Hiromichi Matsushita, Naoki Hasegawa, Yasunori Sato, Mitsuru Murata

npj Vaccines (Springer Science and Business Media LLC) 8 ( 1 ) 2023.03

Abstract

Tools that can be used to estimate antibody waning following COVID-19 vaccinations can facilitate an understanding of the current immune status of the population. In this study, a two-compartment-based mathematical model is formulated to describe the dynamics of the anti-SARS-CoV-2 antibody in healthy adults using serially measured waning antibody concentration data obtained in a prospective cohort study of 673 healthcare providers vaccinated with two doses of BNT162b2 vaccine. The datasets of 165 healthcare providers and 292 elderly patients with or without hemodialysis were used for external validation. Internal validation of the model demonstrated 97.0% accuracy, and external validation of the datasets of healthcare workers, hemodialysis patients, and nondialysis patients demonstrated 98.2%, 83.3%, and 83.8% accuracy, respectively. The internal and external validations demonstrated that this model also fits the data of various populations with or without underlying illnesses. Furthermore, using this model, we developed a smart device application that can rapidly calculate the timing of negative seroconversion.

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Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination.

Uwamino Y, Nagashima K, Yoshifuji A, Suga S, Nagao M, Fujisawa T, Ryuzaki M, Takemoto Y, Namkoong H, Wakui M, Matsushita H, Hasegawa N, Sato Y, Murata M

NPJ vaccines 8 ( 1 ) 33 2023.03

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Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination

Uwamino Yoshifumi, Nagashima Kengo, Yoshifuji Ayumi, Suga Shigeru, Nagao Mizuho, Fujisawa Takao, Ryuzaki Munekazu, Takemoto Yoshiaki, Namkoong Ho, Wakui Masatoshi, Matsushita Hiromichi, Hasegawa Naoki, Sato Yasunori, Murata Mitsuru

NPJ VACCINES 8 ( 1 ) 2023.03

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Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine.

Yoshifumi Uwamino, Takashi Yokoyama, Yasunori Sato, Ayako Shibata, Toshinobu Kurafuji, Akiko Tanabe, Masayo Noguchi, Tomoko Arai, Akemi Ohno, Hiromitsu Yokota, Ho Namkoong, Tomoyasu Nishimura, Kenjiro Kosaki, Naoki Hasegawa, Masatoshi Wakui, Mitsuru Murata, Hiromichi Matsushita

Vaccine 41 ( 9 ) 1545 - 1549 2023.02

ISSN 0264-410X

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose. UMIN Clinical Trials Registry ID: UMIN000043340.

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Diagnostic significance of secondary bacteremia in patients with COVID-19.

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 29 ( 4 ) 422 - 426 2023.01

ISSN 1341-321X

OBJECTIVES: We investigated the occurrence of non-respiratory bacterial and fungal secondary infections, causative organisms, impact on clinical outcomes, and association between the secondary pathogens and mortality in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: This was a retrospective cohort study that included data from inpatients with COVID-19 from multiple centers participating in the Japan COVID-19 Taskforce (April 2020 to May 2021). We obtained demographic, epidemiological, and microbiological data throughout the course of hospitalization and analyzed the cases of COVID-19 complicated by non-respiratory bacterial infections. RESULTS: Of the 1914 patients included, non-respiratory bacterial infections with COVID-19 were diagnosed in 81 patients (4.2%). Of these, 59 (3.1%) were secondary infections. Bacteremia was the most frequent bacterial infection, occurring in 33 cases (55.9%), followed by urinary tract infections in 16 cases (27.1%). Staphylococcus epidermidis was the most common causative organism of bacteremia. Patients with COVID-19 with non-respiratory secondary bacterial infections had significantly higher mortality, and a multivariate logistic regression analysis demonstrated that those with bacteremia (aOdds Ratio = 15.3 [5.97-39.1]) were at higher risk of death. Multivariate logistic regression analysis showed that age, male sex, use of steroids to treat COVID-19, and intensive care unit admission increased the risk for nosocomial bacteremia. CONCLUSIONS: Secondary bacteremia is an important complication that may lead to poor prognosis in cases with COVID-19. An appropriate medical management strategy must be established, especially for patients with concomitant predisposing factors.

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Benefits and risks of haematopoietic stem cell transplantation for systemic sclerosis: A systematic review and meta-analysis

K Higashitani, K Takase-Minegishi, R Yoshimi, Y Kirino, N Hamada, ...

Modern Rheumatology 33 (2), 330-337 2023

Characteristics of patients with COVID-19 who have deteriorating chest X-ray findings within 48 hours: a retrospective cohort study

T Kusumoto, S Chubachi, H Namkoong, H Tanaka, H Lee, S Otake, ...

2023

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

H Tanaka, S Chubachi, T Asakura, H Namkoong, S Azekawa, S Otake, ...

International Journal of Infectious Diseases 2023

Clinical significance of prediabetes, undiagnosed diabetes and diagnosed diabetes on critical outcomes in COVID‐19: Integrative analysis from the Japan COVID‐19 task force

T Fukushima, S Chubachi, H Namkoong, T Asakura, H Tanaka, H Lee, ...

Diabetes, Obesity and Metabolism 25 (1), 144-155 2023

Immune checkpoint inhibitor–induced arthralgia is tightly associated with improved overall survival in cancer patients

A Maeda, K Takase-Minegishi, Y Kirino, N Hamada, Y Kunishita, ...

Rheumatology 62 (4), 1451-1459 2023

Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination

Y Uwamino, K Nagashima, A Yoshifuji, S Suga, M Nagao, T Fujisawa, ...

npj Vaccines 8 (1), 33 2023

Incidence and Risk of Hematological Adverse Events Associated With Immune Checkpoint Inhibitors: A Systematic Literature Review and Meta-Analysis

T Ohashi, K Takase-Minegishi, A Maeda, N Hamada, R Yoshimi, Y Kirino, ...

Journal of Hematology 12 (2), 66-74 2023

Radiological Pleuroparenchymal Fibroelastosis Pattern in Nontuberculous Mycobacterial Pulmonary Disease: A Multicenter Retrospective Study

H Tanaka, T Asakura, S Okamori, K Furuuchi, M Yagi, K Yagi, I Hase, ...

B28. SOLVING THE PUZZLE OF BRONCHIECTASIS AND NONTUBERCULOUS MYCOBACTERIA … 2023

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: Report based on findings from the Japan COVID-19 Task Force.

Mayuko Watase, Katsunori Masaki, Shotaro Chubachi, Ho Namkoong, Hiromu Tanaka, Ho Lee, Takahiro Fukushima, Shiro Otake, Kensuke Nakagawara, Tatsuya Kusumoto, Takanori Asakura, Hirofumi Kamata, Makoto Ishii, Naoki Hasegawa, Yoshitaka Oyamada, Norihiro Harada, Tetsuya Ueda, Soichiro Ueda, Takashi Ishiguro, Ken Arimura, Fukuki Saito, Takashi Yoshiyama, Yasushi Nakano, Yoshikazu Mutoh, Yusuke Suzuki, Ryuya Edahiro, Hirohito Sano, Yasunori Sato, Yukinori Okada, Ryuji Koike, Yuko Kitagawa, Katsushi Tokunaga, 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 128 121 - 127 2022.12

ISSN 1201-9712

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors of severe coronavirus disease 2019 (COVID-19). However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 Task Force between February 2020 and December 2021. PY and COPD status were self-reported by patients. Patients were classified into the non-COPD (n=1151) and COPD (n=115) groups; the non-COPD group was further classified into <10 PY (n=293), 10-30 PY (n=497), and >30 PY (n=361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY=7.8%, 10-30 PY=12.3%, >30 PY=15.2%, COPD=26.1%; p<0.001). Significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY=2.11, COPD=4.14) and multivariate (OR: >30 PY=2.38; COPD=7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 y. CONCLUSIONS: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

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Incidence of hepatotoxicity associated with addition of immune checkpoint blockade to systemic solid tumor therapy: a meta-analysis of phase 3 randomized controlled trials

Fujiwara Yu, Horita Nobuyuki, Harrington Matthew, Namkoong Ho, Miyashita Hirotaka, Galsky Matthew D.

CANCER IMMUNOLOGY IMMUNOTHERAPY 71 ( 12 ) 2837 - 2848 2022.12

ISSN 0340-7004

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