Details of a Researcher - KURONUMA Kouji

Papers - KURONUMA Kouji

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The Soluble Lectin Families as Novel Biomarkers for COVID-19 Pneumonia.

Haruka Takenaka, Atsushi Saito, Koji Kuronuma, Keigo Moniwa, Hirotaka Nishikiori, Satoshi Takahashi, Hirofumi Chiba

In vivo (Athens, Greece) 37 ( 4 ) 1721 - 1728 2023 [International journal]

BACKGROUND/AIM: The lung-specific soluble lectins, SP-A and SP-D have been clinically used to diagnose interstitial lung disease, but their clinical significance in COVID-19 remains controversial. This study was undertaken to determine their association with other lectins (MBL and FCN1), disease severity, and radiographs in COVID-19 patients. PATIENTS AND METHODS: A total of 131 patients with COVID-19 admitted in the Sapporo Medical University Hospital between May 22 and September 19, 2021, were enrolled in the study. Data including demographics, medical history, symptoms, signs, laboratory findings, and radiological images were collected from the patients' medical records. Chest computed tomography (CT) scanning was performed at admission. Serum levels of surfactant protein A and D (SP-A and SP-D), mannose-binding lectin (MBL) and ficolin1 (FCN1) were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Compared to the control group, the COVID-19 group had significantly higher serum SP-A and FCN1 levels on admission (SP-A: 59.60±38.89 vs. 35.61±11.22 ng/ml; p<0.01, FCN1: 542.45±506.04 vs. 250.6±161.1 ng/ml; p<0.01). The severe group in COVID-19 had significantly higher serum SP-D and lower MBL levels than the non-severe group (SP-D: 141.7±155.7 vs. 61.41±54.54 ng/ml; p<0.01, MBL: 1,670±1,240 vs. 2,170±1,140 ng/ml; p<0.05). SP-D strongly reflected the degree of imaging findings, whereas SP-A showed a significant correlation, albeit slightly weaker than SP-D. Conversely, MBL and FNC1 were not significantly correlated with imaging findings. CONCLUSION: Among soluble serum lectins, SP-A and SP-D may be more sensitive to CT findings than reported disease biomarkers such as IL-6, LDH, and CRP due to their lung-specific characteristics.

DOI PubMed

COVID-19における血清レクチン値の臨床バイオマーカーとしての有用性についての検討

齋藤充史, 黒沼幸治, 富樫篤生, 藤谷好弘, 高橋聡

日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集 ( 日本感染症学会東日本地方会・日本化学療法学会東日本支部 ) 71回・69回 125 - 125 2022.10

当院における10年間のvanC保有腸球菌菌血症の特徴から見る治療において重要なこと

藤谷好弘, 佐藤勇樹, 富樫篤生, 齋藤充史, 黒沼幸治, 高橋聡

日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集 ( 日本感染症学会東日本地方会・日本化学療法学会東日本支部 ) 71回・69回 118 - 118 2022.10

男性COVID-19患者の血清テストステロン値は重症度と関連する

黒沼幸治, 鈴木瑛真, 村井良精, 中江舞美, 藤谷好弘, 齋藤充史, 高橋聡

Pneumocystis jirovecii Pneumonia Associated with COVID-19 in Patients with Interstitial Pneumonia.

Tomoyuki Takahashi, Atsushi Saito, Koji Kuronuma, Hirotaka Nishikiori, Hirofumi Chiba

Medicina (Kaunas, Lithuania) 58 ( 9 ) 2022.08 [International journal]

Here, we report two cases of patients with interstitial pneumonia (IP) on steroids who developed Pneumocystis jirovecii pneumonia (PJP) following coronavirus disease 2019 (COVID-19) infection. Case 1: A 69-year-old man on 10 mg of prednisolone (PSL) daily for IP developed new pneumonia shortly after his COVID-19 infection improved and was diagnosed with PJP based on chest computed tomography (CT) findings and elevated serum β-D-glucan levels. Trimethoprim-sulfamethoxazole (TMP-SMZ) was administered, and the pneumonia resolved. Case 2: A 70-year-old woman taking 4 mg/day of PSL for IP and rheumatoid arthritis developed COVID-19 pneumonia, which resolved mildly, but her pneumonia flared up and was diagnosed as PJP based on CT findings, elevated β-D-glucan levels, and positive polymerase chain reaction for P. jirovecii DNA in the sputum. The autopsy revealed diffuse alveolar damage, increased collagen fiver and fibrotic foci, mucinous component accumulation, and the presence of a P. jirovecii cyst. In conclusion, steroids and immunosuppressive medications are well-known risk factors for PJP. Patients with IP who have been taking these drugs for a long time are frequently treated with additional steroids for COVID-19; thus, PJP complications should be avoided in such cases.

DOI PubMed

Viral load may impact the diagnostic performance of nasal swabs in nucleic acid amplification test and quantitative antigen test for SARS-CoV-2 detection.

Yoshihiro Fujiya, Yuki Sato, Yuki Katayama, Shinya Nirasawa, Mikako Moriai, Masachika Saeki, Yuki Yakuwa, Ikumi Kitayama, Koichi Asanuma, Koji Kuronuma, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 ( 11 ) 1590 - 1593 2022.08 [International journal]

INTRODUCTION: Compared to nasopharyngeal swabs (NPS), there has been insufficient evaluation of the diagnostic performance of nasal swabs (NS) for the detection of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the nucleic acid amplification test (NAAT) and quantitative SARS-CoV-2 antigen test (QAT). METHODS: We prospectively compared healthcare worker-collected and flocked NS within nine days after symptom onset to paired NPS to detect SARS-CoV-2 in NAAT and QAT on the fully automated Lumipulse system. The agreement between sample types was evaluated, and cycle threshold (Ct) values and antigen levels were used as surrogate viral load measures. RESULTS: Sixty sets of NPS and NS samples were collected from 40 patients with COVID-19. The overall agreements between NAAT and QAT samples were 76.7% and 65.0%, respectively. In NAAT, the Ct value of NS was significantly higher, 5.9, than that of NPS. Thirty-nine (95.1%) NS tested positive in 41 positive-paired NPS with Ct ≤ 30. The negative correlation was observed between antigen levels of NS in QAT and Ct values of NS in NAAT (r = -0.88). In QAT, the antigen level of NS was significantly lower than that of NPS. Thirty-six (90.0%) NS tested positive in 40 positive-paired NPS with antigen levels >100 pg/mL, which were collected significantly earlier than those with antigen levels ≤100 pg/mL. CONCLUSIONS: In NAAT and QAT, NS had limited performance in detecting SARS-CoV-2 compared to NPS. However, NS may be helpful for patients with COVID-19 with high viral loads or those in the early stages of the illness.

DOI PubMed

Genotypes and transmission routes of noroviruses causing sporadic acute gastroenteritis among adults and children, Japan, 2015-2019.

Saho Honjo, Koji Kuronuma, Yoshihiro Fujiya, Mami Nakae, Susumu Ukae, Hiroshi Nihira, Masaki Yamamoto, Yusuke Akane, Kenji Kondo, Satoshi Takahashi, Hirokazu Kimura, Hiroyuki Tsutsumi, Yukihiko Kawasaki, Takeshi Tsugawa

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 104 105348 - 105348 2022.08 [International journal]

Noroviruses (NoVs) are major causes of acute viral gastroenteritis at all ages worldwide. The molecular epidemiology of sporadic cases remains poorly understood, especially in adults. Additionally, no studies have analyzed the transmission route in sporadic acute gastroenteritis. In this study, we investigated cases of very mild sporadic NoV acute gastroenteritis in adults (medical staff) who do not visit the outpatient clinic and child outpatients. We also evaluated genotype differences between adults and children and possible transmission routes in adults during 5 years. The number of NoV positives were 58 in adults and 124 in children. In adults, the NoV positivity rate in this study was higher (64.4%) than that in previous reports of outpatients (10%) and inpatients (5%) in the United State. This finding suggested that the NoV positivity rate might be high in adults with very mild acute gastroenteritis. In adults, human-to-human transmission rates from children and food-borne transmission (raw oysters) were 21.6% (11/51) and 19.6% (10/51), respectively. Among adults, GII.2, GII.4, and GII.17 were the predominant genotypes, with rates of 32.7%, 30.9%, and 21.8%, respectively. Among children, GII.4 and GII.2 were the predominant genotypes, with rates of 45.5% and 40.6%, respectively. GII.17 was only detected in 0.8% (1/123) of children. Trends in NoV genotypes are expected to differ depending on the patient's age. Investigating sporadic cases including the patient's background (age and transmission route) may be helpful to monitor the trend of NoV strains, forecast prevalent NoV GII genotypes, and develop NoV vaccines.

DOI PubMed

Does the timing of saliva collection affect the diagnosis of SARS-CoV-2 infection?

Yuki Katayama, Ryosei Murai, Mikako Moriai, Shinya Nirasawa, Masachika Saeki, Yuki Yakuwa, Yuki Sato, Koichi Asanuma, Yoshihiro Fujiya, Koji Kuronuma, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 ( 7 ) 1012 - 1014 2022.07 [International journal]

We evaluated the optimal timing of saliva sample collection to diagnose the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We obtained 150 saliva samples at four specific time points from 13 patients with confirmed SARS-CoV-2 infection. The time points were (1) early morning (immediately after waking), (2) immediately after breakfast before tooth brushing, (3) 2 h after breakfast, and (4) before lunch. On the 2nd hospital day, patients collected saliva at the four time points by themselves. We collected samples at two time points, (1) and (3), from the 3rd hospital day to day 9 following symptom onset. In 52 samples collected at the four time points, there was no significant difference. Meanwhile, there was no significant difference in the positive proportion or the viral load between the two time points in both analyses by the day from symptom onset and by all samples. In this study, there was no difference in the positive proportions in saliva collected at various time points within 9 days after symptom onset. The timing of saliva collection was not affected by the diagnosis of SARS-CoV-2 infection.

DOI PubMed

Comparative study of rapid antigen testing and two nucleic acid amplification tests for influenza virus detection.

Yuki Sato, Shinya Nirasawa, Masachika Saeki, Yuki Yakuwa, Mayumi Ono, Ryo Kobayashi, Hirotaka Nakafuri, Ryosei Murai, Yoshihiro Fujiya, Koji Kuronuma, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 ( 7 ) 1033 - 1036 2022.07 [International journal]

INTRODUCTION: This study aimed to evaluate rapid antigen detection (RAD) and rapid nucleic acid amplification tests (NAATs) to detect influenza virus (IV). METHODS: The conventional RAD test (Quick Chaser Flu A, B: QC), using silver amplified immunochromatography (Quick Chaser Auto Flu A, B: QCA), as well as two NAATs (Xpert Xpress Flu/RSV: Xpert, cobas Influenza A/B & RSV: cobas) were evaluated using nasopharyngeal swabs from suspected cases of influenza. A reference method was performed using real-time reverse transcription polymerase chain reaction according to the manual of the Japanese National Institute of Infectious Disease (NIID). RESULTS: From a total of 177 samples, 51 were positive according to the NIID assay. The kappa (κ) coefficient in Xpert and cobas for influenza A virus (IAV)/influenza B virus (IBV) was 1.00, which was the highest among the four detection assays. However, the κ coefficients in QC and QCA for IAV/IBV were 0.71-0.77 and 0.87-0.89, respectively. The sensitivities of the RAD tests were 41.7% in QC and 50.0% in QCA at < 6 h after onset, and 100.0% in both QC and QCA at 24-48 h after onset. The cycle threshold (Ct) values were significantly lower in the group in which all detection assays were positive for IAV. CONCLUSIONS: Xpert and cobas have comparable analytical performances and are highly useful as influenza virus detection assays. QC and QCA could show false negatives frequently in the early stage of infection and when viral load is low.

DOI PubMed

COVID-19肺炎重症度予測マーカーとしてのIL-6、INF-λ3、NGALの検討

黒沼幸治, 中江舞美, 藤谷好弘, 高橋聡, 齋藤充史, 安田健人, 千葉弘文

日本化学療法学会雑誌 ( (公社)日本化学療法学会 ) 70 ( Suppl.A ) 299 - 299 2022.05

COVID-19 臨床経過予測因子 COVID-19肺炎重症度予測マーカーとしてのIL-6、INF-λ3、NGALの検討

齋藤充史, 安田健人, 黒沼幸治, 中江舞美, 藤谷好弘, 高橋聡, 千葉弘文

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 11 ( 増刊 ) 153 - 153 2022.04

胸部X線写真から線維化性間質性肺疾患を検出するAIソフトウェアの性能検証研究

錦織博貴, 黒沼幸治, 廣田健一, 鈴木朋浩, 池田貴美之, 森勇樹, 浅井悠一郎, 本田聖和, 千葉弘文

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 11 ( 増刊 ) 301 - 301 2022.04

COVID-19 臨床経過予測因子 COVID-19肺炎重症度予測マーカーとしてのIL-6、INF-λ3、NGALの検討

齋藤充史, 安田健人, 黒沼幸治, 中江舞美, 藤谷好弘, 高橋聡, 千葉弘文

日本呼吸器学会誌 ( (一社)日本呼吸器学会 ) 11 ( 増刊 ) 153 - 153 2022.04

N-glycosylation regulates MET processing and signaling.

Atsushi Saitou, Yoshihiro Hasegawa, Naoki Fujitani, Shigeru Ariki, Yasuaki Uehara, Ukichiro Hashimoto, Atsushi Saito, Koji Kuronuma, Kunio Matsumoto, Hirofumi Chiba, Motoko Takahashi

Cancer science 113 ( 4 ) 1292 - 1304 2022.01 [International journal]

MET, the receptor for the hepatocyte growth factor (HGF), is strongly associated with resistance to tyrosine kinase inhibitors, key drugs that are used in the therapy of non-small cell lung cancer. MET contains 11 potential N-glycosylation sites, but the site-specific roles of these N-glycans have not been elucidated. We report herein that these N-glycans regulate the proteolytic processing of MET and HGF induced MET signaling, and that this regulation is site specific. Inhibitors of N-glycosylation were found to suppress the processing and trafficking of endogenous MET in H1975 and EBC-1 lung cancer cells and exogenous MET in CHO-K1 cells. We purified the recombinant extracellular domain of human MET and determined the site-specific N-glycan structures and occupancy using mass spectrometry. The results indicated that most sites were fully glycosylated and that the dominant population was the complex-type. To examine the effects of the deletion of N-glycans of MET, we prepared endogenous-MET-knockout Flp-In CHO cells and transfected them with a series of N-glycan deletion mutants of MET. The results showed that several N-glycans are implicated in the processing of MET. The findings also suggested that the N-glycans of the SEMA domain of MET positively regulate HGF signaling, and the N-glycans of the region other than the SEMA domain negatively regulate HGF signaling. Processing, cell surface expression, and signaling were significantly suppressed in the case of the all-N-glycan deletion mutant. The overall findings suggest that N-glycans of MET affect the status and the function of the receptor in a site-specific manner.

DOI PubMed

ファビピラビルおよびデキサメタゾン投与開始時期とCOVID-19臨床転帰の関連性

伊部裕太, 石郷友之, 藤居賢, 藤谷好弘, 黒沼幸治, 高橋聡

日本化学療法学会雑誌 ( (公社)日本化学療法学会 ) 70 ( 1 ) 164 - 165 2022.01

Self-reported Smell and Taste Disorders in Patients With COVID-19: A Japanese Single-center Study.

Keisuke Yamamoto, Yoshihiro Fujiya, Koji Kuronuma, Noriko Ogasawara, Tsuyoshi Ohkuni, Shin-Ichi Yokota, Satoshi Takahashi, Kenichi Takano

In vivo (Athens, Greece) 36 ( 2 ) 918 - 924 2022 [International journal]

BACKGROUND/AIM: Smell and taste disorders are among the most common symptoms of COVID-19. However, the relationship between smell and taste disorders and systemic symptoms is not fully understood in Japan. PATIENTS AND METHODS: Questionnaires were mailed to 105 of 111 COVID-19 patients who were hospitalized at our hospital between March and July 2020 in Japan. RESULTS: A total of 74 patients (response rate: 70.5%) completed the survey. Of these, six patients (8.1%) presented with smell disorders only, 16 (21.6%) presented with taste disorders only, and 17 (23.0%) presented with both smell and taste disorders. The mean Visual Analog Scale for smell and taste was 0.5 and 20, respectively, at the time of the most severe symptoms. CONCLUSION: Among COVID-19 patients in Japan, smell and taste disorders are often followed by fever and may not be the first symptoms. Sense of smell is particularly impaired. These symptoms often improve, although they sometimes persist for a long time as sequelae.

DOI PubMed

【肺免疫から肺疾患を考える】肺疾患とマイクロバイオーム

齋藤充史, 黒沼幸治, 千葉弘文

呼吸器内科 ( (有)科学評論社 ) 40 ( 6 ) 551 - 556 2021.12

COVID-19肺炎におけるバイオマーカーとしての血清SP-AおよびSP-Dの有用性

千葉弘文, 齋藤充史, 黒沼幸治, 茂庭慶悟, 高橋弘毅

日本肺サーファクタント・界面医学会雑誌 ( 日本肺サーファクタント・界面医学会 ) 52 31 - 31 2021.10

新型コロナウイルスN501Y変異株感染入院患者が従来の退院基準を満たした日におけるCt値および抗原量に関する検討

藤谷好弘, 佐藤勇樹, 韮澤慎也, 中村広士, 中江舞美, 津川毅, 黒沼幸治, 高橋聡, 片山雄貴, 米澤仁, 村井良精, 盛合美加子, 四十坊典晴

病原微生物検出情報月報 ( 国立感染症研究所 ) 42 ( 10 ) 233 - 234 2021.10

Early favipiravir treatment was associated with early defervescence in non-severe COVID-19 patients.

Satoshi Fujii, Yuta Ibe, Tomoyuki Ishigo, Hirotoshi Inamura, Yusuke Kunimoto, Yoshihiro Fujiya, Koji Kuronuma, Hiromasa Nakata, Masahide Fukudo, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 7 ) 1051 - 1057 2021.04 [International journal]

INTRODUCTION: The antiviral drug favipiravir has been shown to have in vitro antiviral activity against severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2). In this study, we investigated the clinical benefits and initiation of favipiravir treatment in patients with non-severe coronavirus-disease-2019 (COVID-19). METHODS: This study was a single-center retrospective cohort study. Receiver operating characteristic curves were drawn to calculate the area under the curve, and the optimal cut-off values for the time to initiate favipiravir treatment were calculated to predict defervescence within seven days. Univariate and multivariate Cox regression analyses were performed to identify potential influencing factors of defervescence. This was defined as a body temperature of less than 37 °C for at least 2 days. RESULTS: Data from 41 patients were used for the efficacy assessment. The days from the onset of fever to defervescence showed a positive correlation with the duration from the onset of fever to initiation of favipiravir treatment (r = 0.548, P < 0.001). The optimal cut-off value was the administration of favipiravir on day 4. Patients were assigned to two groups based on the optimal cut-off value from onset to initiation of favipiravir treatment: early treatment group (within 4-days) and late treatment group (more than 4-days). In the multivariate analysis, when adjusted for age, sex, and days from onset to initiation of favipiravir treatment, the significant factors were male sex and days of initiation of the favipiravir treatment. CONCLUSIONS: We recommend that if favipiravir is to be used for treatment, it should be initiated as early as possible.

DOI PubMed

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Papers - KURONUMA Kouji