Faculty Profiles - SAKAMOTO Koji

Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of IPF. Reviewed International coauthorship International journal

Koji Sakamoto, Taiki Furukawa, Yasuhiko Yamano, Kensuke Kataoka, Ryo Teramachi, Anjali Walia, Atsushi Suzuki, Masahide Inoue, Yoshio Nakahara, Changwan Ryu, Naozumi Hashimoto, Yasuhiro Kondoh

The European respiratory journal Vol. 57 ( 1 ) 2021.1

Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors. Reviewed International journal

Jun Fukihara, Koji Sakamoto, Junji Koyama, Takayasu Ito, Shingo Iwano, Masahiro Morise, Masahiro Ogawa, Yasuhiro Kondoh, Tomoki Kimura, Naozumi Hashimoto, Yoshinori Hasegawa

Clinical lung cancer Vol. 20 ( 6 ) page： 442 - + 2019.11

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated. PATIENTS AND METHODS: A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors. RESULTS: Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP. CONCLUSION: Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.

DOI： 10.1016/j.cllc.2019.07.006

Prognostic Awareness and Knowledge of Acute Exacerbation in Patients Dying with Interstitial Lung Disease: A Nationwide Survey. Reviewed International journal

Takafumi Koyauchi, Tomoyuki Fujisawa, Mitsunori Miyashita, Masanori Mori, Tatsuya Morita, Shusuke Yazawa, Norimichi Akiyama, Satoshi Hagimoto, Yoshinobu Matsuda, Ryo Tachikawa, Hideki Yasui, Masaru Suzuki, Yuichiro Asai, Manabu Ono, Yuichiro Kimura, Shinya Ohkouchi, Yoshinori Tanino, Keishi Sugino, Tomoya Tateishi, Motoyasu Kato, Atsushi Miyamoto, Yoshinobu Saito, Susumu Sakamoto, Masato Kono, Koshi Yokomura, Shiro Imokawa, Koji Sakamoto, Yuko Waseda, Tomohiro Handa, Noboru Hattori, Kazuki Anabuki, Kazuhiro Yatera, Yuki Shundo, Tomoaki Hoshino, Noriho Sakamoto, Yasuhiro Kondoh, Hiromi Tomioka, Keisuke Tomii, Yoshikazu Inoue, Takafumi Suda

Annals of the American Thoracic Society Vol. 22 ( 3 ) page： 395 - 402 2025.3

Language：English Publishing type：Research paper (scientific journal)

RATIONALE: Accurate prognostic awareness (PA) and knowledge of the disease are critical for decision-making regarding treatment options, advance care planning, and end-of-life care. However, they have not been investigated in patients with interstitial lung disease (ILD). OBJECTIVES: To determine the prevalence of patients with ILD who have accurate PA and/or knowledge of acute exacerbation. In addition, to determine whether accurate PA is associated with end-of-life medical interventions and quality of dying and death. METHODS: Through a nationwide bereavement survey, we examined the prevalence of accurate PA and knowledge of acute exacerbation (AE) in patients with ILD who died in acute general hospitals between January 2018 and February 2020. Patients' PA and knowledge were assessed from the perspective of the bereaved. We also quantified the quality of dying and death from the perspective of the bereaved using three scales, the Good Death Inventory, the Quality of Dying and Death (QODD) questionnaire, and the single-item QODD overall score, and obtained information on end-of-life interventions from the electronic medical record. We examined the associations of accurate PA with end-of-life interventions and quality of dying and death. RESULTS: A total of 296 patients whose caregivers completed questionnaires were analyzed. One hundred sixty-three patients (55.1%, 95% confidence interval [CI] = 49.2-60.8) who died of ILD had accurate PA and 138 (46.9%, 95% CI = 35.9-47.4) recognized that their disease could have AE. Multivariate regression analysis showed that accurate PA was associated with significantly fewer intensive care unit (ICU) deaths (odds ratio = 0.28, 95% CI = 0.10-0.82, P = 0.02). Patients with accurate PA had better quality of dying and death on all the three scales. CONCLUSIONS: Approximately half of the patients who died of ILD did not recognize that their disease could lead to death or AE. The lower number of ICU deaths and better quality of dying and death in patients with accurate PA suggest the potential benefits of obtaining accurate PA in patients with ILD.

DOI： 10.1513/AnnalsATS.202405-495OC

Metagenomic Analysis of Lung Microbiome in Patients With Interstitial Lung Diseases and Sarcoidosis: An Experimental Study Reviewed

Takeuchi, S; Kawada, J; Suzuki, A; Sakamoto, K; Fukuda, Y; Horiba, K; Suzuki, T; Torii, Y; Shindo, Y; Ito, Y

HEALTH SCIENCE REPORTS Vol. 8 ( 2 ) page： e70328 2025.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Health Science Reports

Background and Aims: Interactions between the lung microbiome and pulmonary epithelium plays a pivotal role in shaping immunity in the lung. Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease (ILD). Some patients with IPF develop episodic acute exacerbations often associated with microbial dysbiosis in the lungs. This study aimed to investigate etiologic agents as well as the lung microbiome in patients with ILDs and sarcoidosis. Methods: This study analyzed 31 patients divided into the IPF (IPF-stable, n = 12), acute exacerbation of ILDs (AE-ILDs, n = 6), and sarcoidosis (n = 13) groups. Bronchoalveolar lavage fluid (BALF) samples were analyzed by RNA-based metagenomic next-generation sequencing (NGS) on an Illumina platform. Results: In total, 87 pathogens were detected using metagenomic NGS at the genus level. Prevotella, Streptococcus, and Veillonella dominated the BALF microbial communities, and sequence reads of these bacteria were abundant, especially in the sarcoidosis group. Conversely, only a small number of bacterial reads were detected in the AE-ILDs group, and the overall proportion of microbial composition differed from that of the other groups. No significant difference was found in community diversity (α-diversity) among the groups, whereas the structural similarity of the microflora (β-diversity) differed significantly between the AE-ILDs and sarcoidosis groups. Conclusions: Bacterial sequence reads in BALF were smaller in both the IPF-stable and AE-ILD groups than in the sarcoidosis group. Dysbiosis in the lung microbiome has been observed in patients with AE-ILD and may be related to the progression of inflammation.

DOI： 10.1002/hsr2.70328

知っておきたい間質性肺疾患の基本～病態生理から治療・合併症・呼吸ケアの注意点まで～

阪本考司

日本呼吸ケア・リハビリテーション学会誌 Vol. 34 ( supplement ) page： 87s_2 - 87s_2 2024.10

Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study. Reviewed International journal

Jun Fukihara, Koji Sakamoto, Yoshiki Ikeyama, Taiki Furukawa, Ryo Teramachi, Kensuke Kataoka, Yasuhiro Kondoh, Naozumi Hashimoto, Makoto Ishii

Respiratory research Vol. 25 ( 1 ) page： 202 - 202 2024.5

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Extracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF. METHODS: Extracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed. RESULTS: mtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p < 0.001) and ≥ 11,194.3 copies/µL at the time of AE (MST: 2.6 vs. 20.0 months, p = 0.03) were associated with shorter survival after BALF collection, even after adjusting for other known prognostic factors. On the other hand, BALF-nucDNA showed different trends in correlation with other clinical variables and did not show any significant association with survival time. CONCLUSIONS: Elevated BALF-mtDNA was associated with a poor prognosis in both IPF and AE-IPF. Of note, at the time of AE, it sharply distinguished survivors from non-survivors. Given the trends shown by analyses for BALF-nucDNA, the elevation of BALF-mtDNA might not simply reflect the impact of cell collapse. Further studies are required to explore the underlying mechanisms and clinical applications of BALF-mtDNA in IPF.

DOI： 10.1186/s12931-024-02828-9

Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease. Reviewed International journal

Tomonori Sato, Taiki Furukawa, Ryo Teramachi, Jun Fukihara, Yasuhiko Yamano, Toshiki Yokoyama, Toshiaki Matsuda, Kensuke Kataoka, Tomoki Kimura, Koji Sakamoto, Makoto Ishii, Yasuhiro Kondoh

Thorax Vol. 79 ( 5 ) page： 422 - 429 2024.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 20<MPAP<25 mm Hg, and ≥25 mm Hg were 26.2%, 60.4% and 86.4%, respectively. In Cox proportional hazards analyses with adjustment for ILD-Gender, Age and Physiology Index, PVR but not MPAP was associated with a higher mortality rate (HR 1.37, 95% CI 1.23 to 1.52, p<0.0001; HR 0.98, 95% CI 0.96 to 1.01, p=0.1671, respectively). PVR>2 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

DOI： 10.1136/thorax-2023-220179

Rapidly progressive interstitial lung disease with positive anti-MDA5 antibody as an immune-related complication of nivolumab: A case report. Reviewed

Kato S, Sakamoto K, Sato T, Kobayashi T, Shindo Y, Morise M, Iwama S, Arima H, Ishii M.

Respiratory Investigation Vol. 62 ( 2 ) page： 313 - 316 2024.2

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy. Reviewed

Kataoka K, Oda K, Takizawa H, Ogura T, Miyamoto A, Inoue Y, Akagawa S, Hashimoto S, Kishaba T, Sakamoto K, Hamada N, Kuwano K, Nakayama M, Ebina M, Enomoto N, Miyazaki Y, Atsumi K, Izumi S, Tanino Y, Ishii H, Ohnishi H, Suda T, Kondoh Y.

Scientific Reports Vol. 13 ( 1 ) page： 13664 2023.8

Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan. International journal

Eriko Fukutani, Keiko Wakahara, Saya Nakamura, Eito Yokoi, Akira Yoshimi, Masayuki Miyazaki, Mariko Nakamura, Yuichiro Shindo, Koji Sakamoto, Shotaro Okachi, Ichidai Tanaka, Nobuyuki Hamajima, Yukihiro Noda, Naozumi Hashimoto, Makoto Ishii

The Journal of asthma : official journal of the Association for the Care of Asthma page： 1 - 12 2023.5

Language：English Publishing type：Research paper (scientific journal)

Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it.Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers.Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence.Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

DOI： 10.1080/02770903.2023.2209173

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? Reviewed

Yonezawa T, Suzuki A, Fukumitsu K, Katano T, Kako H, Ishii M, Niimi A, Imaizumi K, Sakamoto K, Omote N, Yamaguchi E.

Respiratory Medicine Case Report Vol. 43 page： 101857 2023.4

Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial. Reviewed International journal

Kensuke Kataoka, Osamu Nishiyama, Takashi Ogura, Yoshihiro Mori, Ryo Kozu, Shinichi Arizono, Tohru Tsuda, Hiromi Tomioka, Keisuke Tomii, Koji Sakamoto, Hiroshi Ishimoto, Michiko Kagajo, Hiroyuki Ito, Kazuya Ichikado, Hajime Sasano, Seiichirou Eda, Machiko Arita, Yasuhiro Goto, Osamu Hataji, Satoshi Fuke, Ryota Shintani, Hirotsugu Hasegawa, Masahiko Ando, Tomoya Ogawa, Masashi Shiraishi, Fumiko Watanabe, Koichi Nishimura, Takuma Sasaki, Shinjiro Miyazaki, Hideo Saka, Yasuhiro Kondoh

Thorax Vol. 78 ( 8 ) page： 784 - 791 2023.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

DOI： 10.1136/thorax-2022-219792

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease triggered by COVID-19: What is the best practice for treatment? Reviewed International journal

Toshiyuki Yonezawa, Atsushi Suzuki, Kensuke Fukumitsu, Takuma Katano, Hisashi Kako, Makoto Ishii, Akio Niimi, Kazuyoshi Imaizumi, Koji Sakamoto, Norihito Omote, Etsuro Yamaguchi

Respiratory medicine case reports Vol. 43 page： 101857 - 101857 2023

Language：English Publishing type：Research paper (scientific journal)

We present a case of 79-year-old female with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) developed an acute exacerbation (AE) triggered by coronavirus disease 2019 (COVID-19). The patient was unresponsive to a combination therapy of remdesivir, dexamethasone, and tocilizumab. Given that a recent multicenter cohort study reported ILD as a poor prognostic contributor in patients with RA and COVID-19, there may be potentially a certain number of patients with AE of RA-ILD triggered by COVID-19. This case highlights the need for a discussion how to treat these patients in a daily clinical practice.

DOI： 10.1016/j.rmcr.2023.101857

DOCK2 is involved in the host genetics and biology of severe COVID-19. International journal

Ho Namkoong, Ryuya Edahiro, Tomomi Takano, Hiroshi Nishihara, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Shuhei Azekawa, Yohei Mikami, Ho Lee, Takanori Hasegawa, Koji Okudela, Daisuke Okuzaki, Daisuke Motooka, Masahiro Kanai, Tatsuhiko Naito, Kenichi Yamamoto, Qingbo S Wang, Ryunosuke Saiki, Rino Ishihara, Yuta Matsubara, Junko Hamamoto, Hiroyuki Hayashi, Yukihiro Yoshimura, Natsuo Tachikawa, Emmy Yanagita, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Ryousuke Aoki, Ai Nakamura, Sonoko Harada, Hitoshi Sasano, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashi Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Ken Suzuki, Yoko Naito, Yu-Chen Liu, Ayako Takuwa, Fuminori Sugihara, James B Wing, Shuhei Sakakibara, Nobuyuki Hizawa, Takayuki Shiroyama, Satoru Miyawaki, Yusuke Kawamura, Akiyoshi Nakayama, Hirotaka Matsuo, Yuichi Maeda, Takuro Nii, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Toshihiro Kishikawa, Shuhei Yamada, Shuhei Kawabata, Noriyuki Kijima, Masatoshi Takagaki, Noah Sasa, Yuya Ueno, Motoyuki Suzuki, Norihiko Takemoto, Hirotaka Eguchi, Takahito Fukusumi, Takao Imai, Munehisa Fukushima, Haruhiko Kishima, Hidenori Inohara, Kazunori Tomono, Kazuto Kato, Meiko Takahashi, Fumihiko Matsuda, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Koji Sakamoto, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-O, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Kazuhiko Katayama, Masumi Ai, Yoshinori Fukui, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Yukinori Okada

Nature Vol. 609 ( 7928 ) page： 754 - + 2022.9

Language：English Publishing type：Research paper (scientific journal)

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

DOI： 10.1038/s41586-022-05163-5

A comprehensible machine learning tool to differentially diagnose idiopathic pulmonary fibrosis from other chronic interstitial lung diseases

Taiki Furukawa, Shintaro Oyama, Hideo Yokota, Yasuhiro Kondoh, Kensuke Kataoka, Takeshi Johkoh, Junya Fukuoka, Naozumi Hashimoto, Koji Sakamoto, Yoshimune Shiratori, Yoshinori Hasegawa

Respirology Vol. 27 ( 9 ) page： 739 - 746 2022.9

CINS: Cell Interaction Network inference from Single cell expression data. Reviewed International coauthorship International journal

Ye Yuan, Carlos Cosme Jr, Taylor Sterling Adams, Jonas Schupp, Koji Sakamoto, Nikos Xylourgidis, Matthew Ruffalo, Jiachen Li, Naftali Kaminski, Ziv Bar-Joseph

PLoS computational biology Vol. 18 ( 9 ) page： e1010468 2022.9

Language：English Publishing type：Research paper (scientific journal)

Studies comparing single cell RNA-Seq (scRNA-Seq) data between conditions mainly focus on differences in the proportion of cell types or on differentially expressed genes. In many cases these differences are driven by changes in cell interactions which are challenging to infer without spatial information. To determine cell-cell interactions that differ between conditions we developed the Cell Interaction Network Inference (CINS) pipeline. CINS combines Bayesian network analysis with regression-based modeling to identify differential cell type interactions and the proteins that underlie them. We tested CINS on a disease case control and on an aging mouse dataset. In both cases CINS correctly identifies cell type interactions and the ligands involved in these interactions improving on prior methods suggested for cell interaction predictions. We performed additional mouse aging scRNA-Seq experiments which further support the interactions identified by CINS.

DOI： 10.1371/journal.pcbi.1010468

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force. Reviewed International journal

Qingbo S Wang, Ryuya Edahiro, Ho Namkoong, Takanori Hasegawa, Yuya Shirai, Kyuto Sonehara, Hiromu Tanaka, Ho Lee, Ryunosuke Saiki, Takayoshi Hyugaji, Eigo Shimizu, Kotoe Katayama, Masahiro Kanai, Tatsuhiko Naito, Noah Sasa, Kenichi Yamamoto, Yasuhiro Kato, Takayoshi Morita, Kazuhisa Takahashi, Norihiro Harada, Toshio Naito, Makoto Hiki, Yasushi Matsushita, Haruhi Takagi, Masako Ichikawa, Ai Nakamura, Sonoko Harada, Yuuki Sandhu, Hiroki Kabata, Katsunori Masaki, Hirofumi Kamata, Shinnosuke Ikemura, Shotaro Chubachi, Satoshi Okamori, Hideki Terai, Atsuho Morita, Takanori Asakura, Junichi Sasaki, Hiroshi Morisaki, Yoshifumi Uwamino, Kosaku Nanki, Sho Uchida, Shunsuke Uno, Tomoyasu Nishimura, Takashri Ishiguro, Taisuke Isono, Shun Shibata, Yuma Matsui, Chiaki Hosoda, Kenji Takano, Takashi Nishida, Yoichi Kobayashi, Yotaro Takaku, Noboru Takayanagi, Soichiro Ueda, Ai Tada, Masayoshi Miyawaki, Masaomi Yamamoto, Eriko Yoshida, Reina Hayashi, Tomoki Nagasaka, Sawako Arai, Yutaro Kaneko, Kana Sasaki, Etsuko Tagaya, Masatoshi Kawana, Ken Arimura, Kunihiko Takahashi, Tatsuhiko Anzai, Satoshi Ito, Akifumi Endo, Yuji Uchimura, Yasunari Miyazaki, Takayuki Honda, Tomoya Tateishi, Shuji Tohda, Naoya Ichimura, Kazunari Sonobe, Chihiro Tani Sassa, Jun Nakajima, Yasushi Nakano, Yukiko Nakajima, Ryusuke Anan, Ryosuke Arai, Yuko Kurihara, Yuko Harada, Kazumi Nishio, Tetsuya Ueda, Masanori Azuma, Ryuichi Saito, Toshikatsu Sado, Yoshimune Miyazaki, Ryuichi Sato, Yuki Haruta, Tadao Nagasaki, Yoshinori Yasui, Yoshinori Hasegawa, Yoshikazu Mutoh, Tomoki Kimura, Tomonori Sato, Reoto Takei, Satoshi Hagimoto, Yoichiro Noguchi, Yasuhiko Yamano, Hajime Sasano, Sho Ota, Yasushi Nakamori, Kazuhisa Yoshiya, Fukuki Saito, Tomoyuki Yoshihara, Daiki Wada, Hiromu Iwamura, Syuji Kanayama, Shuhei Maruyama, Takashi Yoshiyama, Ken Ohta, Hiroyuki Kokuto, Hideo Ogata, Yoshiaki Tanaka, Kenichi Arakawa, Masafumi Shimoda, Takeshi Osawa, Hiroki Tateno, Isano Hase, Shuichi Yoshida, Shoji Suzuki, Miki Kawada, Hirohisa Horinouchi, Fumitake Saito, Keiko Mitamura, Masao Hagihara, Junichi Ochi, Tomoyuki Uchida, Rie Baba, Daisuke Arai, Takayuki Ogura, Hidenori Takahashi, Shigehiro Hagiwara, Genta Nagao, Shunichiro Konishi, Ichiro Nakachi, Koji Murakami, Mitsuhiro Yamada, Hisatoshi Sugiura, Hirohito Sano, Shuichiro Matsumoto, Nozomu Kimura, Yoshinao Ono, Hiroaki Baba, Yusuke Suzuki, Sohei Nakayama, Keita Masuzawa, Shinichi Namba, Takayuki Shiroyama, Yoshimi Noda, Takayuki Niitsu, Yuichi Adachi, Takatoshi Enomoto, Saori Amiya, Reina Hara, Yuta Yamaguchi, Teruaki Murakami, Tomoki Kuge, Kinnosuke Matsumoto, Yuji Yamamoto, Makoto Yamamoto, Midori Yoneda, Kazunori Tomono, Kazuto Kato, Haruhiko Hirata, Yoshito Takeda, Hidefumi Koh, Tadashi Manabe, Yohei Funatsu, Fumimaro Ito, Takahiro Fukui, Keisuke Shinozuka, Sumiko Kohashi, Masatoshi Miyazaki, Tomohisa Shoko, Mitsuaki Kojima, Tomohiro Adachi, Motonao Ishikawa, Kenichiro Takahashi, Takashi Inoue, Toshiyuki Hirano, Keigo Kobayashi, Hatsuyo Takaoka, Kazuyoshi Watanabe, Naoki Miyazawa, Yasuhiro Kimura, Reiko Sado, Hideyasu Sugimoto, Akane Kamiya, Naota Kuwahara, Akiko Fujiwara, Tomohiro Matsunaga, Yoko Sato, Takenori Okada, Yoshihiro Hirai, Hidetoshi Kawashima, Atsuya Narita, Kazuki Niwa, Yoshiyuki Sekikawa, Koichi Nishi, Masaru Nishitsuji, Mayuko Tani, Junya Suzuki, Hiroki Nakatsumi, Takashi Ogura, Hideya Kitamura, Eri Hagiwara, Kota Murohashi, Hiroko Okabayashi, Takao Mochimaru, Shigenari Nukaga, Ryosuke Satomi, Yoshitaka Oyamada, Nobuaki Mori, Tomoya Baba, Yasutaka Fukui, Mitsuru Odate, Shuko Mashimo, Yasushi Makino, Kazuma Yagi, Mizuha Hashiguchi, Junko Kagyo, Tetsuya Shiomi, Satoshi Fuke, Hiroshi Saito, Tomoya Tsuchida, Shigeki Fujitani, Mumon Takita, Daiki Morikawa, Toru Yoshida, Takehiro Izumo, Minoru Inomata, Naoyuki Kuse, Nobuyasu Awano, Mari Tone, Akihiro Ito, Yoshihiko Nakamura, Kota Hoshino, Junichi Maruyama, Hiroyasu Ishikura, Tohru Takata, Toshio Odani, Masaru Amishima, Takeshi Hattori, Yasuo Shichinohe, Takashi Kagaya, Toshiyuki Kita, Kazuhide Ohta, Satoru Sakagami, Kiyoshi Koshida, Kentaro Hayashi, Tetsuo Shimizu, Yutaka Kozu, Hisato Hiranuma, Yasuhiro Gon, Namiki Izumi, Kaoru Nagata, Ken Ueda, Reiko Taki, Satoko Hanada, Kodai Kawamura, Kazuya Ichikado, Kenta Nishiyama, Hiroyuki Muranaka, Kazunori Nakamura, Naozumi Hashimoto, Keiko Wakahara, Sakamoto Koji, Norihito Omote, Akira Ando, Nobuhiro Kodama, Yasunari Kaneyama, Shunsuke Maeda, Takashige Kuraki, Takemasa Matsumoto, Koutaro Yokote, Taka-Aki Nakada, Ryuzo Abe, Taku Oshima, Tadanaga Shimada, Masahiro Harada, Takeshi Takahashi, Hiroshi Ono, Toshihiro Sakurai, Takayuki Shibusawa, Yoshifumi Kimizuka, Akihiko Kawana, Tomoya Sano, Chie Watanabe, Ryohei Suematsu, Hisako Sageshima, Ayumi Yoshifuji, Kazuto Ito, Saeko Takahashi, Kota Ishioka, Morio Nakamura, Makoto Masuda, Aya Wakabayashi, Hiroki Watanabe, Suguru Ueda, Masanori Nishikawa, Yusuke Chihara, Mayumi Takeuchi, Keisuke Onoi, Jun Shinozuka, Atsushi Sueyoshi, Yoji Nagasaki, Masaki Okamoto, Sayoko Ishihara, Masatoshi Shimo, Yoshihisa Tokunaga, Yu Kusaka, Takehiko Ohba, Susumu Isogai, Aki Ogawa, Takuya Inoue, Satoru Fukuyama, Yoshihiro Eriguchi, Akiko Yonekawa, Keiko Kan-O, Koichiro Matsumoto, Kensuke Kanaoka, Shoichi Ihara, Kiyoshi Komuta, Yoshiaki Inoue, Shigeru Chiba, Kunihiro Yamagata, Yuji Hiramatsu, Hirayasu Kai, Koichiro Asano, Tsuyoshi Oguma, Yoko Ito, Satoru Hashimoto, Masaki Yamasaki, Yu Kasamatsu, Yuko Komase, Naoya Hida, Takahiro Tsuburai, Baku Oyama, Minoru Takada, Hidenori Kanda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Shozo Yoshida, Shinji Ogura, Shinji Abe, Yuta Kono, Yuki Togashi, Hiroyuki Takoi, Ryota Kikuchi, Shinichi Ogawa, Tomouki Ogata, Shoichiro Ishihara, Arihiko Kanehiro, Shinji Ozaki, Yasuko Fuchimoto, Sae Wada, Nobukazu Fujimoto, Kei Nishiyama, Mariko Terashima, Satoru Beppu, Kosuke Yoshida, Osamu Narumoto, Hideaki Nagai, Nobuharu Ooshima, Mitsuru Motegi, Akira Umeda, Kazuya Miyagawa, Hisato Shimada, Mayu Endo, Yoshiyuki Ohira, Masafumi Watanabe, Sumito Inoue, Akira Igarashi, Masamichi Sato, Hironori Sagara, Akihiko Tanaka, Shin Ohta, Tomoyuki Kimura, Yoko Shibata, Yoshinori Tanino, Takefumi Nikaido, Hiroyuki Minemura, Yuki Sato, Yuichiro Yamada, Takuya Hashino, Masato Shinoki, Hajime Iwagoe, Hiroshi Takahashi, Kazuhiko Fujii, Hiroto Kishi, Masayuki Kanai, Tomonori Imamura, Tatsuya Yamashita, Masakiyo Yatomi, Toshitaka Maeno, Shinichi Hayashi, Mai Takahashi, Mizuki Kuramochi, Isamu Kamimaki, Yoshiteru Tominaga, Tomoo Ishii, Mitsuyoshi Utsugi, Akihiro Ono, Toru Tanaka, Takeru Kashiwada, Kazue Fujita, Yoshinobu Saito, Masahiro Seike, Hiroko Watanabe, Hiroto Matsuse, Norio Kodaka, Chihiro Nakano, Takeshi Oshio, Takatomo Hirouchi, Shohei Makino, Moritoki Egi, Yosuke Omae, Yasuhito Nannya, Takafumi Ueno, Tomomi Takano, Kazuhiko Katayama, Masumi Ai, Atsushi Kumanogoh, Toshiro Sato, Naoki Hasegawa, Katsushi Tokunaga, Makoto Ishii, Ryuji Koike, Yuko Kitagawa, Akinori Kimura, Seiya Imoto, Satoru Miyano, Seishi Ogawa, Takanori Kanai, Koichi Fukunaga, Yukinori Okada

Nature communications Vol. 13 ( 1 ) page： 4830 - 4830 2022.8

Language：English Publishing type：Research paper (scientific journal)

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

DOI： 10.1038/s41467-022-32276-2

COVID-19-Triggered Acute Exacerbation of IPF, an Underdiagnosed Clinical Entity With Two-Peaked Respiratory Failure: A Case Report and Literature Review Reviewed International journal

Goto Yosuke, Sakamoto Koji, Fukihara Jun, Suzuki Atsushi, Omote Norihito, Ando Akira, Shindo Yuichiro, Hashimoto Naozumi

FRONTIERS IN MEDICINE Vol. 9 page： 815924 2022.2

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers in Medicine

Because severe coronavirus disease 2019 (COVID-19) affects the respiratory system and develops into respiratory failure, patients with pre-existing chronic lung disorders, such as idiopathic pulmonary fibrosis (IPF), are thought to be at high risk of death. Patients with IPF often suffer from a lethal complication, acute exacerbation (AE), a significant part of which is assumed to be triggered by respiratory viral infection. However, whether mild to moderate COVID-19 can trigger AE in patients with IPF remains unknown. This is the case report of a 60-year-old man with a 4-year history of IPF who successfully recovered from moderate COVID-19 but subsequently developed more severe respiratory failure, which was considered to be a COVID-19-triggered acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). It is important to be aware of the risk of AE-IPF after COVID-19 and to properly manage this deadly complication of IPF. Recent literature reporting cases with chronic interstitial lung diseases which developed respiratory failure by complications with COVID-19 is also reviewed and discussed.

DOI： 10.3389/fmed.2022.815924