Details of a Researcher - Asakura, Takanori

Papers - Asakura, Takanori

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CT-derived vertebral bone mineral density is a useful biomarker to predict COVID-19 outcome.

Shuhei Azekawa, Tomoki Maetani, Shotaro Chubachi, Takanori Asakura, Naoya Tanabe, Yusuke Shiraishi, Ho Namkoong, Hiromu Tanaka, Takashi Shimada, Takahiro Fukushima, Shiro Otake, Kensuke Nakagawara, Mayuko Watase, Hideki Terai, Mamoru Sasaki, Soichiro Ueda, Yukari Kato, Norihiro Harada, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Yoshitake Yamada, Masahiro Jinzaki, Toyohiro Hirai, Yukinori Okada, Ryuji Koike, Makoto Ishii, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Bone 184 117095 - 117095 2024.07

ISSN 87563282

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death. We examined the effects of COVID-19 severity on the change of BMD over time. This multicenter retrospective cohort study enrolled 1132 inpatients with COVID-19 from the Japan COVID-19 Task Force database between February 2020 and September 2022. The bone CT values of the 4th, 7th, and 10th thoracic vertebrae were measured from chest CT images. The average of these values was defined as BMD. Furthermore, a comparative analysis was conducted between the BMD on admission and its value 3 months later. The low BMD group had a higher proportion of critical outcomes than did the high BMD group. In a subanalysis stratifying patients by epidemic wave according to onset time, critical outcomes were higher in the low BMD group in the 1st-4th waves. Multivariable logistic analysis of previously reported factors associated with COVID-19 severity revealed that low BMD, chronic kidney disease, and diabetes were independently associated with critical outcomes. At 3 months post-infection, patients with oxygen demand during hospitalization showed markedly decreased BMD than did those on admission. Low BMD in patients with COVID-19 may help predict severe disease after the disease onset. BMD may decrease over time in patients with severe COVID-19, and the impact on sequelae symptoms should be investigated in the future.

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Development of allergic bronchopulmonary aspergillosis in a patient with nontuberculous mycobacterial-pulmonary disease successfully treated with dupilumab: A case report and literature review.

Ryuta Onozato, Jun Miyata, Takanori Asakura, Ho Namkoong, Koichiro Asano, Naoki Hasegawa, Koichi Fukunaga

Respirology case reports 12 ( 7 ) e01432 2024.07

Pulmonary manifestations in patients with allergic bronchopulmonary aspergillosis (ABPA) and nontuberculous mycobacterial-pulmonary disease (NTM-PD) include bronchiectasis and mucus plugging. A 68-year-old woman, treated with antibiotics and inhaled corticosteroids for NTM-PD and asthma, presented with fever and wheezing. ABPA was diagnosed based on laboratory findings (elevated peripheral blood eosinophil counts and serum total IgE levels and positive Aspergillus-specific IgE and IgG) and imaging observation of a high-attenuation mucus plug. Systemic prednisolone was avoided to prevent NTM-PD progression. Dupilumab, a monoclonal antibody that blocks IL-4/13, was introduced to improve the clinical findings. Herein, we discuss the pathophysiological mechanisms underlying this rare comorbidity.

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Lung volume measurement using chest CT in COVID-19 patients: a cohort study in Japan.

Shiro Otake, Yusuke Shiraishi, Shotaro Chubachi, Naoya Tanabe, Tomoki Maetani, Takanori Asakura, Ho Namkoong, Takashi Shimada, Shuhei Azekawa, Kensuke Nakagawara, Hiromu Tanaka, Takahiro Fukushima, Mayuko Watase, Hideki Terai, Mamoru Sasaki, Soichiro Ueda, Yukari Kato, Norihiro Harada, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Yoshitake Yamada, Masahiro Jinzaki, Toyohiro Hirai, Yukinori Okada, Ryuji Koike, Makoto Ishii, Naoki Hasegawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

BMJ open respiratory research 11 ( 1 ) 2024.04

OBJECTIVE: This study aimed to investigate the utility of CT quantification of lung volume for predicting critical outcomes in COVID-19 patients. METHODS: This retrospective cohort study included 1200 hospitalised patients with COVID-19 from 4 hospitals. Lung fields were extracted using artificial intelligence-based segmentation, and the percentage of the predicted (%pred) total lung volume (TLC (%pred)) was calculated. The incidence of critical outcomes and posthospitalisation complications was compared between patients with low and high CT lung volumes classified based on the median percentage of predicted TLCct (n=600 for each). Prognostic factors for residual lung volume loss were investigated in 208 patients with COVID-19 via a follow-up CT after 3 months. RESULTS: The incidence of critical outcomes was higher in the low TLCct (%pred) group than in the high TLCct (%pred) group (14.2% vs 3.3%, p<0.0001). Multivariable analysis of previously reported factors (age, sex, body mass index and comorbidities) demonstrated that CT-derived lung volume was significantly associated with critical outcomes. The low TLCct (%pred) group exhibited a higher incidence of bacterial infection, heart failure, thromboembolism, liver dysfunction and renal dysfunction than the high TLCct (%pred) group. TLCct (%pred) at 3 months was similarly divided into two groups at the median (71.8%). Among patients with follow-up CT scans, lung volumes showed a recovery trend from the time of admission to 3 months but remained lower in critical cases at 3 months. CONCLUSION: Lower CT lung volume was associated with critical outcomes, posthospitalisation complications and slower improvement of clinical conditions in COVID-19 patients.

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Asthma is a risk factor for general fatigue of long COVID in Japanese nation-wide cohort study.

Keeya Sunata, Jun Miyata, Hideki Terai, Emiko Matsuyama, Mayuko Watase, Ho Namkoong, Takanori Asakura, Katsunori Masaki, Shotaro Chubachi, Keiko Ohgino, Ichiro Kawada, Norihiro Harada, Hitoshi Sasano, Ai Nakamura, Yu Kusaka, Takehiko Ohba, Yasushi Nakano, Kazumi Nishio, Yukiko Nakajima, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Makoto Ishii, Koichi Fukunaga

Allergology international : official journal of the Japanese Society of Allergology 73 ( 2 ) 206 - 213 2024.04

ISSN 13238930

BACKGROUND: Multiple prolonged symptoms are observed in patients who recover from an acute COVID-19 infection, which is defined as long COVID. General fatigue is frequently observed in patients with long COVID during acute and post-acute phases. This study aimed to identify the specific risk factors for general fatigue in long COVID. METHODS: Hospitalized patients with COVID-19 aged over 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps. RESULTS: Among prolonged symptoms through 1-year follow-ups, general fatigue was the most interfering symptom in daily life. Patients with protracted fatigue at all follow-up periods had lower quality of life scores at the 12-month follow-up. Univariate logistic regression analysis of the presence or absence of general fatigue at the 3-month, 6-month, and 12-month follow-ups identified asthma, younger age, and female sex as risk factors for prolonged fatigue. Multivariable logistic regression analysis revealed that asthma was an independent risk factor for persistent fatigue during the 12-month follow-up period. Longitudinal changes in the symptoms of patients with or without asthma demonstrated that general fatigue, not cough and dyspnea, was significantly prolonged in patients with asthma. CONCLUSIONS: In a Japanese population with long COVID, prolonged general fatigue was closely linked to asthma. A preventive approach against COVID-19 is necessary to avoid sustained fatigue and minimize social and economic losses in patients with asthma.

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Levels of environmental contamination with SARS-CoV-2 in hospital rooms and salivary viral loads of patients with coronavirus disease 2019.

Hidehito Matsui, Yusuke Suzuki, Sohei Nakayama, Takanori Asakura, Osamu Takeuchi, Kaori Kusatsugu, Chihiro Ueda, Eri Nakajima, Yumiko Suzuki, Harumi Endo, Miho Sugamata, Yukiko Takarabe, Yukie Yamaguchi, Kazuhito Horie, Yoshikazu Kobayashi, Satoshi Kuronuma, Yasuo Imoto, Hideaki Hanaki

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 4 ) 315 - 322 2024.04

ISSN 1341321X

BACKGROUND: Clarifying the presence of viable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rather than SARS-CoV-2 viral RNA in inpatient rooms is important for infection control of coronavirus disease 2019 (COVID-19). In this study, we investigated levels of viral RNA and viable virus on environmental surfaces and in patient saliva. METHODS: Environmental samples from 23 sites in hospital rooms were collected every other day until patient discharge. Saliva specimens and samples from the inner surface of patient masks were also collected. Additionally, environmental samples were collected from 46 sites in hospital rooms on discharge day. The samples were examined using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and plaque assays. RESULTS: The 10 enrolled cases were classified as mild COVID-19, and patients were discharged after 6-9 days. The viral RNA was detected in 12.4% (105/849) of serially collected environmental samples during hospitalization, whereas viable virus was detected only in 0.47% (4/849), which were from sinks and tap levers. Although all patients recovered, three cases retained viable virus in the last saliva specimen collected. In the 15 discharged rooms, viral RNA was detected in 6.6% (45/682) of the samples, and viable virus was detected in only one sample from the sink. CONCLUSIONS: Although environmental surfaces surrounding patients with COVID-19 were frequently contaminated with viral RNA, the presence of viable virus was rare and limited only to areas around sinks. These results suggest that contact infection risk via fomites in hospital rooms is extremely rare.

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Calcium channel blockers may reduce the development of long COVID in females.

Takuya Ozawa, Ryusei Kimura, Hideki Terai, Ryo Takemura, Ho Namkoong, Masahiro Kondo, Keitaro Fukuda, Kazuma Yagi, Takanori Asakura, Katsunori Masaki, Shotaro Chubachi, Jun Miyata, Keiko Ohgino, Ichiro Kawada, Junko Kagyo, Toshio Odani, Naota Kuwahara, Ichiro Nakachi, Makoto Ishii, Yasunori Sato, Koichi Fukunaga

Hypertension research : official journal of the Japanese Society of Hypertension 47 ( 4 ) 934 - 943 2024.04

ISSN 09169636

With the rising numbers of patients infected with severe acute respiratory syndrome coronavirus 2, long coronavirus disease 2019 (COVID-19)-a sequelae of COVID-19-has become a major problem. Different sexes and age groups develop different long COVID symptoms, and the risk factors for long COVID remain unclear. Therefore, we performed subgroup analyses of patients with COVID-19, classifying them into different groups. In this multicenter cohort study, using an original questionnaire, we examined patients (≥18 years old) diagnosed with COVID-19 from November 2020 to March 2022 and hospitalized at participating medical facilities. In total, 1066 patients were registered (361 female, 620 male). Hypertension was the most common comorbidity (n = 344; 32.5%). Females with hypertension were significantly less likely to develop long COVID symptoms than those without hypertension (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27-0.98; p = 0.043). In females, Ca channel blocker administration, rather than having hypertension, was significantly associated with reductions in the frequency of alopecia (OR 0.14, 95% CI 0.03-0.67, p = 0.015), memory impairment (OR 0.14, 95% CI 0.02-0.82, p = 0.029), sleeping disorders (OR 0.17, 95% CI 0.04-0.67, p = 0.012), tinnitus (OR 0.23, 95% CI 0.05-0.98, p = 0.047), sputum (OR 0.31, 95% CI 0.10-0.92, p = 0.035), and fever (OR 0.33, 95% CI 0.12-0.93, p = 0.036). Several long COVID symptoms, including alopecia, were significantly negatively associated with Ca channel-blocker administration in female patients with long COVID. Calcium channel blockers may reduce the development of long COVID in females.

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Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study

Matsubara Y., Kiyohara H., Mikami Y., Nanki K., Namkoong H., Chubachi S., Tanaka H., Azekawa S., Sugimoto S., Yoshimatsu Y., Sujino T., Takabayashi K., Hosoe N., Sato T., Ishii M., Hasegawa N., Okada Y., Koike R., Kitagawa Y., Kimura A., Imoto S., Miyano S., Ogawa S., Fukunaga K., Kanai T., Chubachi S., Fukushima T., Tanaka H., Lee H., Otake S., Nakagawara K., Morita A., Watase M., Sakurai K., Ogawa T., Kusumoto T., Masaki K., Kabata H., Ikemura S., Okamori S., Terai H., Kamata H., Uchida S., Uno S., Hasegawa N., Takahashi K., Sasano H., Kitagawa Y., Harada N., Takagi H., Nakamura A., Naito T., Hiki M., Matsushita Y., Aoki R., Harada S., Sasaki J., Morisaki H., Uwamino Y., Mikami Y., Ishihara R., Sugimoto S., Yoshimatsu Y., Nishimura T., Sato T., Ueda T., Azuma M., Saito R., Sado T., Miyazaki Y., Sato R., Haruta Y., Nagasaki T., Hasegawa Y., Yasui Y., Ueda S., Tada A., Miyawaki M., Yamamoto M., Yoshida E., Hayashi R., Nagasaka T., Arai S., Kaneko Y., Sasaki K., Ishiguro T., Isono T., Shibata S., Matsui Y., Hosoda C., Takano K., Nishida T., Kobayashi Y., Takaku Y., Takayanagi N., Tagaya E.

Journal of Gastroenterology 59 ( 3 ) 195 - 208 2024.03

ISSN 09441174

Background: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. Methods: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. Results: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53–0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42–0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53–0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42–0.92). Conclusions: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

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Prognostic significance of hypertension history and blood pressure on admission in Japanese patients with coronavirus disease 2019: integrative analysis from the Japan COVID-19 Task Force.

Kaori Sakurai, Shotaro Chubachi, Takanori Asakura, Ho Namkoong, Hiromu Tanaka, Shuhei Azekawa, Takashi Shimada, Shiro Otake, Kensuke Nakagawara, Takahiro Fukushima, Ho Lee, Mayuko Watase, 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

Hypertension research : official journal of the Japanese Society of Hypertension 47 ( 3 ) 639 - 648 2024.03

ISSN 09169636

The effect of preexisting hypertension on coronavirus disease 2019 (COVID-19) prognosis remains controversial. Additionally, no studies have compared the association between blood pressure (BP) indices on admission and COVID-19 outcomes using preexisting hypertension status. Therefore, this study aimed to investigate the association between preexisting hypertension and COVID-19 outcomes in Japanese patients with COVID-19 and assess the impact of BP indices on admission on clinical outcomes in patients with and without preexisting hypertension. Preexisting hypertension presence was confirmed based on the patient's clinical history. Critical outcomes were defined as high-flow oxygen use, non-invasive and invasive positive-pressure ventilation, extracorporeal membrane oxygenation, or death during hospitalization. Preexisting hypertension was observed in 64.6% of the patients. Multivariable logistic regression analysis of severe COVID-19 risk factors indicated that preexisting hypertension was independently associated with critical outcomes [adjusted odds ratio (OR): 1.35; 95% confidence interval (CI): 1.05-1.73]. Low or high BP and high pulse pressure on admission were associated with critical outcomes in patients without preexisting hypertension [OR for systolic BP < 100 mmHg: 2.13, 95% CI: 1.21-3.75; OR for high BP stage 2 (160-179 systolic and/or 100-109 mmHg diastolic BP): 2.13, 95% CI: 1.27-3.58; OR for pulse pressure ≥60 mmHg: 1.68, 95% CI: 1.14-2.48]. Preexisting hypertension is a risk factor for critical outcomes in Japanese patients with COVID-19. BP indices are useful biomarkers for predicting COVID-19 outcomes, particularly in patients without preexisting hypertension. Thus, hypertension history, systolic BP, and pulse pressure should be assessed to predict severe COVID-19 outcomes.

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Integrated assessment of computed tomography density in pectoralis and erector spinae muscles as a prognostic biomarker for coronavirus disease 2019.

Kensuke Nakagawara, Yusuke Shiraishi, Shotaro Chubachi, Naoya Tanabe, Tomoki Maetani, Takanori Asakura, Ho Namkoong, Hiromu Tanaka, Takashi Shimada, Shuhei Azekawa, Shiro Otake, Takahiro Fukushima, Mayuko Watase, Hideki Terai, Mamoru Sasaki, Soichiro Ueda, Yukari Kato, Norihiro Harada, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Yoshitake Yamada, Masahiro Jinzaki, Toyohiro Hirai, Yukinori Okada, Ryuji Koike, Makoto Ishii, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Clinical nutrition (Edinburgh, Scotland) 43 ( 3 ) 815 - 824 2024.03

ISSN 02615614

UNLABELLED: BACKGROUND ＆ AIMS: Muscle quantification using chest computed tomography (CT) is a useful prognostic biomarker for coronavirus disease 2019 (COVID-19). However, no studies have evaluated the clinical course through comprehensive assessment of the pectoralis and erector spinae muscles. Therefore, we compared the impact of the areas and densities of these muscles on COVID-19 infection outcome. METHODS: This multicenter retrospective cohort study was conducted by the COVID-19 Task Force. A total of 1410 patients with COVID-19 were included, and data on the area and density of the pectoralis and erector spinae muscles on chest CT were collected. The impact of each muscle parameter on the clinical outcome of COVID-19 was stratified according to sex. The primary outcome was the percentage of patients with severe disease, including those requiring oxygen supplementation and those who died. Additionally, 167 patients were followed up for changes in muscle parameters at three months and for the clinical characteristics in case of reduced CT density. RESULTS: For both muscles, low density rather than muscle area was associated with COVID-19 severity. Regardless of sex, lower erector spinae muscle density was associated with more severe disease than pectoralis muscle density. The muscles were divided into two groups using the receiver operating characteristic curve of CT density, and the population was classified into four (Group A: high CT density for both muscles, Group B: low CT density for pectoralis and high for erector spinae muscle. Group C: high CT density for pectoralis and low for erector spinae muscle, Group D: low CT density for both muscles). In univariate analysis, Group D patients exhibited worse outcomes than Group A (OR: 2.96, 95% CI: 2.03-4.34 in men; OR: 3.02, 95% CI: 2.66-10.4 in women). Multivariate analysis revealed that men in Group D had a significantly more severe prognosis than those in Group A (OR: 1.82, 95% CI: 1.16-2.87). Moreover, Group D patients tended to have the highest incidence of other complications due to secondary infections and acute kidney injury during the clinical course. Longitudinal analysis of both muscle densities over three months revealed that patients with decreased muscle density over time were more likely to have severe cases than those who did not. CONCLUSIONS: Muscle density, rather than muscle area, predicts the clinical outcomes of COVID-19. Integrated assessment of pectoralis and erector spinae muscle densities demonstrated higher accuracy in predicting the clinical course of COVID-19 than individual assessments.

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Pneumocystis Pneumonia in Locally Advanced Breast Cancer Despite Prophylactic Use of Trimethoprim-Sulfamethoxazole During Prednisolone Treatment for a Pembrolizumab-Induced Immune-Related Adverse Event: A Case Report.

Yudai Kaneda, Kenji Gonda, Takanori Asakura, Masahiro Wada, Toyoaki Sawano, Tomohiro Kurokawa, Kazunoshin Tachibana, Akihiko Ozaki

Cureus 16 ( 3 ) e56868 2024.03

Pneumocystis pneumonia (PCP) primarily affects immunosuppressed patients, with trimethoprim-sulfamethoxazole (TMP-SMX) commonly used for prophylaxis. However, there is insufficient information on PCP occurrence despite TMP-SMX prophylaxis. We encountered a 57-year-old woman with locally advanced breast cancer developing PCP despite prophylactic intake of TMP-SMX, during treatment with prednisolone for Stevens-Johnson syndrome (SJS) induced by pembrolizumab. This case underscores the need to pay attention to the possibility of PCP development even during TMP-SMX prophylaxis. Dosage and duration adjustments according to the patient's condition and weight may be required.

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Cluster analysis of long COVID in Japan and association of its trajectory of symptoms and quality of life.

Fumimaro Ito, Hideki Terai, Masahiro Kondo, Ryo Takemura, Ho Namkoong, Takanori Asakura, Shotaro Chubachi, Keita Masuzawa, Sohei Nakayama, Yusuke Suzuki, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Naoto Minematsu, Tadashi Manabe, Takahiro Fukui, Yohei Funatsu, Hidefumi Koh, Katsunori Masaki, Keiko Ohgino, Jun Miyata, Ichiro Kawada, Makoto Ishii, Yasunori Sato, Koichi Fukunaga

BMJ open respiratory research 11 ( 1 ) 2024.02

BACKGROUND: Multiple prolonged symptoms observed in patients who recovered from COVID-19 are defined as long COVID. Although diverse phenotypic combinations are possible, they remain unclear. This study aimed to perform a cluster analysis of long COVID in Japan and clarify the association between its characteristics and background factors and quality of life (QOL). METHODS: This multicentre prospective cohort study collected various symptoms and QOL after COVID-19 from January 2020 to February 2021. This study included 935 patients aged ≥18 years with COVID-19 at 26 participating medical facilities. Hierarchical cluster analysis was performed using 24 long COVID symptom at 3 months after diagnosis. RESULTS: Participants were divided into the following five clusters: numerous symptoms across multiple organs (cluster 1, n=54); no or minor symptoms (cluster 2, n=546); taste and olfactory disorders (cluster 3, n=76); fatigue, psychoneurotic symptoms and dyspnoea (low prevalence of cough and sputum) (cluster 4, n=207) and fatigue and dyspnoea (high prevalence of cough and sputum) (cluster 5, n=52). Cluster 1 included elderly patients with severe symptoms, while cluster 3 included young female with mild symptoms. No significant differences were observed in the comorbidities. Cluster 1 showed the most impaired QOL, followed by clusters 4 and 5; these changes as well as the composition of symptoms were observed over 1 year. CONCLUSIONS: We identified patients with long COVID with diverse characteristics into five clusters. Future analysis of these different pathologies could result in individualised treatment of long COVID. TRIAL REGISTRATION NUMBER: The study protocol is registered at UMIN clinical trials registry (UMIN000042299).

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Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis (NCFB).

Takanori Asakura, Kenichi Okuda, Gang Chen, Hong Dang, Takafumi Kato, Yu Mikami, Stephen A Schworer, Rodney C Gilmore, Giorgia Radicioni, Padraig Hawkins, Selene Margarita Barbosa Cardenas, Minako Saito, Anne Marie Cawley, Gabriela De la Cruz, Michael Chua, Neil E Alexis, Yohei Masugi, Peadar G Noone, Carla M P Ribeiro, Mehmet Kesimer, Kenneth N Olivier, Naoki Hasegawa, Scott H Randell, Wanda K O'Neal, Richard C Boucher

American journal of respiratory and critical care medicine 209 ( 4 ) 374 - 389 2024.02

ISSN 1073449X

Rationale: Non-cystic fibrosis bronchiectasis (NCFB) may originate in bronchiolar regions of the lung. Accordingly, there is a need to characterize the morphology and molecular characteristics of NCFB bronchioles. Objective: Test the hypothesis that NCFB exhibits a major component of bronchiolar disease manifest by mucus plugging and ectasia. Methods: Morphologic criteria and region-specific epithelial gene expression, measured histologically and by RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC), identified proximal and distal bronchioles in excised NCFB lungs. RNA-ISH and IHC assessed bronchiolar mucus accumulation and mucin gene expression. CRISPR-Cas9-mediated IL-1R1 knockout in human bronchial epithelial (HBE) cultures tested IL-1α/β contributions to mucin production. Spatial transcriptional profiling characterized NCFB distal bronchiolar gene expression. Measurements and Main Results: Bronchiolar perimeters and lumen areas/section area were increased in proximal, but not distal, bronchioles in NCFB vs control lungs, suggesting proximal bronchiolectasis. In NCFB, mucus plugging was observed in ectatic proximal bronchioles and associated non-ectatic distal bronchioles in sections with disease. MUC5AC and MUC5B mucins were upregulated in NCFB proximal bronchioles, whereas MUC5B was selectively upregulated in distal bronchioles. Bronchiolar mucus plugs were populated by IL-1β-expressing macrophages. NCFB sterile sputum supernatants induced HBE MUC5B/MUC5AC expression that was >80% blocked by IL-1R1 ablation. Spatial transcriptional profiling identified upregulation of genes associated with secretory cells, hypoxia, interleukin pathways, IL-1β-producing macrophages in mucus plugs, and downregulation of epithelial ciliogenesis genes. Conclusions: NCFB exhibits distinctive proximal and distal bronchiolar disease. Both bronchiolar regions exhibit bronchiolar secretory cell features and mucus plugging but differ in mucin gene regulation and ectasia.

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Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences.

Atsuho Morita, Ho Namkoong, Yoshifumi Uwamino, Satoshi Mitarai, Akio Aono, Takanori Asakura, Kazuma Yagi, Hiromu Tanaka, Shuhei Azekawa, Kensuke Nakagawara, Masanori Kaji, Genta Nagao, Hirofumi Kamata, Hiromichi Matsushita, Koichi Fukunaga, Naoki Hasegawa

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 2 ) 159 - 163 2024.02

ISSN 1341321X

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.

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COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

Takeshi Arashiro, Maki Miwa, Hidenori Nakagawa, Junpei Takamatsu, Kunihiro Oba, Satoshi Fujimi, Hitoshi Kikuchi, Takamasa Iwasawa, Fumiko Kanbe, Keisuke Oyama, Masayuki Kanai, Yoshitaka Ogata, Takanori Asakura, Takahiro Asami, Keiko Mizuno, Manabu Sugita, Torahiko Jinta, Yusuke Nishida, Hideaki Kato, Kazuaki Atagi, Taiki Higaki, Yoshio Nakano, Takeya Tsutsumi, Kent Doi, Shu Okugawa, Akihiro Ueda, Akira Nakamura, Toru Yoshida, Kaoru Shimada-Sammori, Keiki Shimizu, Yasuo Fujita, Yasumi Okochi, Kentaro Tochitani, Asuka Nakanishi, Hiroshi Rinka, Daisuke Taniyama, Asase Yamaguchi, Toshio Uchikura, Maiko Matsunaga, Hiromi Aono, Masanari Hamaguchi, Kentaro Motoda, Sohei Nakayama, Kei Yamamoto, Hideaki Oka, Katsushi Tanaka, Takeshi Inoue, Mieko Kobayashi, Shigeki Fujitani, Maki Tsukahara, Saki Takeda, Ashley Stucky, Tadaki Suzuki, Chris Smith, Martin Hibberd, Koya Ariyoshi, Yuji Fujino, Yuzo Arima, Shinhiro Takeda, Satoru Hashimoto, Motoi Suzuki

Vaccine 42 ( 3 ) 677 - 688 2024.01

ISSN 0264410X

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

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Epicardial adipose tissue measured from analysis of adipose tissue area using chest CT imaging is the best potential predictor of COVID-19 severity.

Takahiro Fukushima, Tomoki Maetani, Shotaro Chubachi, Naoya Tanabe, Takanori Asakura, Ho Namkoong, Hiromu Tanaka, Takashi Shimada, Shuhei Azekawa, Shiro Otake, Kensuke Nakagawara, Mayuko Watase, Yusuke Shiraishi, Hideki Terai, Mamoru Sasaki, Soichiro Ueda, Yukari Kato, Norihiro Harada, Shoji Suzuki, Shuichi Yoshida, Hiroki Tateno, Yoshitake Yamada, Masahiro Jinzaki, Toyohiro Hirai, Yukinori Okada, Ryuji Koike, Makoto Ishii, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga

Metabolism: clinical and experimental 150 155715 - 155715 2024.01

ISSN 00260495

BACKGROUND: Computed tomography (CT) imaging is widely used for diagnosing and determining the severity of coronavirus disease 2019 (COVID-19). Chest CT imaging can be used to calculate the epicardial adipose tissue (EAT) and upper abdominal visceral adipose tissue (Abd-VAT) areas. The EAT is the main source of inflammatory cytokines involved in chest inflammatory diseases; thus, the EAT area might be a more useful severity predictor than the Abd-VAT area for COVID-19. However, to the best of our knowledge, there are no large-scale reports that sufficiently consider this issue. In addition, there are no reports on the characteristics of patients with normal body mass index (BMI) and high adipose tissue. AIM: The purpose of this study was to analyze whether the EAT area, among various adipose tissues, was the most associated factor with COVID-19 severity. Using a multicenter COVID-19 patient database, we analyzed the associations of chest subcutaneous, chest visceral, abdominal subcutaneous, and Abd-VAT areas with COVID-19 outcomes. In addition, the clinical significance of central obesity, commonly disregarded by BMI, was examined. METHODS: This retrospective cohort study evaluated patients with COVID-19 aged ≥18 years In Japan. Data including from chest CT images collected between February 2020 and October 2022 in four hospitals of the Japan COVID-19 Task Force were analyzed. Patient characteristics and COVID-19 severity were compared according to the adipose tissue areas (chest and abdominal subcutaneous adipose tissue [Chest-SAT and Abd-SAT], EAT, and Abd-VAT) calculated from chest CT images. RESULTS: We included 1077 patients in the analysis. Patients with risk factors of severe COVID-19 such as old age, male sex, and comorbidities had significantly higher areas of EAT and Abd-VAT. High EAT area but not high Abd-VAT area was significantly associated with COVID-19 severity (adjusted odds ratio (aOR): 2.66, 95 % confidence interval [CI]: 1.19-5.93). There was no strong correlation between BMI and VAT. Patients with high VAT area accounted for 40.7 % of the non-obesity population (BMI < 25 kg/m2). High EAT area was also significantly associated with COVID-19 severity in the non-obesity population (aOR: 2.50, 95 % CI: 1.17-5.34). CONCLUSIONS: Our study indicated that VAT is significantly associated with COVID-19 severity and that EAT is the best potential predictor for risk stratification in COVID-19 among adipose tissue areas. Body composition assessment using EAT is an appropriate marker for identifying obesity patients overlooked by BMI. Considering the next pandemic of the global health crisis, our findings open new avenues for implementing appropriate body composition assessments based on CT imaging.

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Upper Respiratory Symptoms as Long COVID: Insight from a Multicenter Cohort Study.

Masahiko Okada, Noriyuki Ishida, Sho Kanzaki, Ichiro Kawada, Kengo Nagashima, Hideki Terai, Gaku Hiruma, Ho Namkoong, Takanori Asakura, Katsunori Masaki, Keiko Ohgino, Jun Miyata, Shotaro Chubachi, Nobuhiro Kodama, Shunsuke Maeda, Satoshi Sakamoto, Masaki Okamoto, Yoji Nagasaki, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Kazuhiro Minami, Rie Hagiwara, Makoto Ishii, Yasunori Sato, Koichi Fukunaga

OTO open 8 ( 1 ) e120 2024.01

OBJECTIVE: This study aimed to investigate the clinical features of long COVID cases presenting with upper respiratory symptoms, a topic not yet fully elucidated. STUDY DESIGN: Prospective cohort study. SETTING: A multicenter study involving 26 medical facilities in Japan. METHODS: Inclusion criteria were patients aged ≥18 years old with a confirmed COVID-19 diagnosis via severe acute respiratory syndrome coronavirus 2 polymerase chain reaction or antigen testing, who were hospitalized at the participating medical facilities. Analyzing clinical information and patient-reported outcomes from 1009 patients were analyzed. The outcome measured the degree of initial symptoms for taste or olfactory disorders and assessed the likelihood of these symptoms persisting as long COVID, as well as the impact on quality of life if the upper respiratory symptoms persisted as long COVID. RESULTS: Patients with high albumin, low C-reactive protein, and low lactate dehydrogenase in laboratory tests tended to experience taste or olfactory disorders as part of long COVID. Those with severe initial symptoms had a higher risk of experiencing residual symptoms at 3 months, with an odds ratio of 2.933 (95% confidence interval [CI], 1.282-6.526) for taste disorders and 3.534 (95% CI, 1.382-9.009) for olfactory disorders. Presence of upper respiratory symptoms consistently resulted in lower quality of life scores. CONCLUSION: The findings from this cohort study suggest that severe taste or olfactory disorders as early COVID-19 symptoms correlate with an increased likelihood of persistent symptoms in those disorders as long COVID.

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Spinal tuberculosis in Afghanistan: A 2019-2020 study of patients in Kabul hospitals

Qaderi F., Mashid I., Gachkar L., Martellucci M., Qaderi S., Ozaki A., Haghbin Toutounchi A., Taheriazam A., Asakura T., Gholipoor Talemi H., Mohammady N., Shabani M.

Public Health Challenges 2 ( 4 ) 2023.12

Background: Tuberculosis (TB) is endemic in many low-income countries, which can affect the spine in 1%–5% of those with an active infection. This study reports the clinical characteristics of patients admitted for spinal TB in Kabul, Afghanistan, a country with very limited resources. Methods: This was a descriptive study among 26 patients treated for spinal TB in three major referral hospitals in Kabul, Afghanistan, between March 2019 and April 2020. The sociodemographic and clinical details, gender, age, site of infection, presenting complaints, signs, and symptoms of the patients were retrieved from their medical records. Summary statistics were analyzed using SPSS version 20. Ethics approval was obtained from the ethics committee of Shahid Beheshti University of Medical Sciences in Tehran, Iran. Results: Data were available for 26 patients with spinal TB admitted consecutively. The mean age of the sample was 38.2 years (SD 17.5), and there were 16 males and 10 females. Median time from symptom onset to hospital admission was 60 days. The most common diagnostic imaging technique used was magnetic resonance imaging (92.3%), followed by computed tomography (7.7%). The majority of the lesions involved the lumbar spine (61.4%), followed by the thoracolumbar spine (30.8%). Back pain was the most common manifestation in 21 patients (80.8%), and varying degrees of neurological impairment were found in 16 (61.5%) patients. There were no deaths among the patients up to the discharge date. Conclusions: This study describes the clinical characteristics of spinal TB among patients in Kabul, Afghanistan. It is essential to strengthen preventive strategies and to improve health awareness about clinical features of spinal TB in patients with chronic back pain even in the absence of signs of TB.

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Longitudinal significance of six-minute walk test in patients with nontuberculous mycobacterial pulmonary disease: an observational study.

Atsuho Morita, Kazuma Yagi, Takanori Asakura, Ho Namkoong, Yasunori Sato, Takunori Ogawa, Tatsuya Kusumoto, Shoji Suzuki, Hiromu Tanaka, Ho Lee, Satoshi Okamori, Shuhei Azekawa, Kensuke Nakagawara, Masanori Kaji, Genta Nagao, Yohei Funatsu, Yoshifumi Kimizuka, Hirofumi Kamata, Tomoyasu Nishimura, Makoto Ishii, Koichi Fukunaga, Naoki Hasegawa

BMC pulmonary medicine 23 ( 1 ) 247 - 247 2023.12

BACKGROUND: The long-term exercise tolerance changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) are of great interest because of its chronic course. This study aimed to characterize the associations between changes over time in six-minute walking test (6MWT) parameters and clinical parameters in patients with NTM-PD. METHODS: Overall, 188 patients with NTM-PD, visiting outpatient clinics at Keio University Hospital from April 2012 to March 2020 were included in the study. Data were collected using the St. George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT), blood tests, and the 6MWT at registration and at least once after that. The association of the anchors and clinical indicators with the 6MWT parameters was assessed. RESULTS: The median age [interquartile range] of the patients was 67 [63-74] years. The median baseline six-minute walk distance (6MWD) and final Borg scale (FBS) were 413 [361-470] m and 1 [0-2], respectively. In the correlation analysis, ΔSGRQ total/year (yr), Δforced vital capacity (FVC, % predicted)/yr, Δforced expiratory volume in 1 s (FEV1, % predicted)/yr, and Δdiffusing capacity for carbon monoxide (DLCO, % predicted)/yr correlated with both Δ6MWD/yr and ΔFBS/yr in the longitudinal analysis (|Rho| > 0.20). When stratified into three quantiles of changes in each anchor, the 6MWT parameters worsened over time in the bottom 25% group by mixed-effects model. Specifically, Δ6MWD was affected by SGRQ activity, SGRQ impacts, PFT (FVC, FEV1, and DLCO), and C-reactive protein (CRP). ΔFBS was affected by all SGRQ components, total score, and PFT. Anchor scores and variables at baseline that worsened Δ6MWD were higher SGRQ scores, lower FVC (% predicted), lower DLCO (% predicted), higher Krebs von den Lungen-6, old age, and undergoing treatment at registration. Similarly, these clinical parameters and elevated CRP, excluding undergoing treatment at registration, worsened ΔFBS. CONCLUSIONS: The decreased walking distance and exacerbation of dyspnea on exertion over time in patients with NTM-PD may reflect a deterioration of health-related quality of life and pulmonary function. Thus, the change in 6MWT over time can be used as an indicator to accurately assess the patient's condition and tailor their healthcare environment.

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Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations.

Kensuke Nakagawara, Atsuho Morita, Ho Namkoong, Hideki Terai, Shotaro Chubachi, Takanori Asakura, Hiromu Tanaka, Fumimaro Ito, Emiko Matsuyama, Masanori Kaji, Ayaka Saito, Hatsuyo Takaoka, Masahiko Okada, Keeya Sunata, Mayuko Watase, Kazuma Yagi, Keiko Ohgino, Jun Miyata, Hirofumi Kamata, Ichiro Kawada, Keigo Kobayashi, Toshiyuki Hirano, Takashi Inoue, Junko Kagyo, Tetsuya Shiomi, Kengo Otsuka, Naoki Miyao, Toshio Odani, Rie Baba, Daisuke Arai, Ichiro Nakachi, Soichiro Ueda, Yohei Funatsu, Hidefumi Koh, Kota Ishioka, Saeko Takahashi, Morio Nakamura, Toshiro Sato, Naoki Hasegawa, Yuko Kitagawa, Takanori Kanai, Makoto Ishii, Koichi Fukunaga

Vaccine: X 15 100381 - 100381 2023.12

We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.

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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 2023.12

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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