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

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

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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Acknowledgments

We would like to thank all participants involved in this study and all the members of the Japan COVID-19 Task Force, who regularly engage in clinical and research work on COVID-19. All the members contributed to this study, and the details of the members of the Japan COVID-19 Task Force are provided in the Supplementary Appendix. We also thank John Daniel from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

The collaborators in the Japan COVID-19 Task Force are listed as follows:

Shotaro Chubachi1, Ho Namkoong1,2, Takahiro Fukushima1, Hiromu Tanaka1, Ho Lee1, Shiro Otake1, Kensuke Nakagawara1, Atsuho Morita1, Mayuko Watase1, Kaori Sakurai1, Takunori Ogawa1, Takuya Kusumoto1, Katsunori Masaki1, Hiroki Kabata1, Shinnosuke Ikemura1, Satoshi Okamori1, Hideki Terai1, Hirofumi Kamata1, Sho Uchida2, Shunsuke Uno2, Naoki Hasegawa2, Kazuhisa Takahashi3, Hitoshi Sasano3, Yuko Kitagawa4, Norihiro Harada5, Haruhi Takagi5, Ai Nakamura5, Toshio Naito6, Makoto Hiki7,8, Yasushi Matsushita9, Ryousuke Aoki10, Sonoko Harada5,11, Junichi Sasaki12, Hiroshi Morisaki13, Yoshifumi Uwamino14, Kosaku Nanki15, Yohei Mikami15, Rino Ishihara15, Yuta Matsubara15, Hiroki Kiyohara15, Shinya Sugimoto15, Yusuke Yoshimatsu15, Tomoyasu Nishimura2,16, Toshiro Sato17, Tetsuya Ueda18, Masanori Azuma18, Ryuichi Saito18, Toshikatsu Sado18, Yoshimune Miyazaki18, Ryuichi Sato18, Yuki Haruta18, Tadao Nagasaki18, Yoshinori Hasegawa18, Yoshinori Yasui19, Soichiro Ueda20, Ai Tada20, Masayoshi Miyawaki20, Masaomi Yamamoto20, Eriko Yoshida20, Reina Hayashi20, Tomoki Nagasaka20, Sawako Arai20, Yutaro Kaneko20, Kana Sasaki20, Takashi Ishiguro21, Taisuke Isono21, Shun Shibata21, Yuma Matsui21, Chiaki Hosoda21, Kenji Takano21, Takashi Nishida21, Yoichi Kobayashi21, Yotaro Takaku21, Noboru Takayanagi21, Etsuko Tagaya22, Ken Arimura22, Masatoshi Kawana23, Yasushi Nakamori24, Kazuhisa Yoshiya24, Fukuki Saito24, Tomoyuki Yoshihara24, Daiki Wada24, Hiromu Iwamura24, Syuji Kanayama24, Shuhei Maruyama24, Takanori Hasegawa25, Kunihiko Takahashi25, Tatsuhiko Anzai25, Satoshi Ito25, Akifumi Endo26, Yuji Uchimura27, Yasunari Miyazaki28, Takayuki Honda28, Tomoya Tateishi28, Shuji Tohda29, Naoya Ichimura29, Kazunari Sonobe29, Chihiro Tani Sassa29, Jun Nakajima29, Masumi Ai30, Takashi Yoshiyama31, Ken Ohta31, Hiroyuki Kokuto31, Hideo Ogata31, Yoshiaki Tanaka31, Kenichi Arakawa31, Masafumi Shimoda31, Takeshi Osawa31, Yasushi Nakano32, Yukiko Nakajima32, Ryusuke Anan32, Ryosuke Arai32, Yuko Kurihara32, Yuko Harada32, Kazumi Nishio32, Yoshikazu Mutoh33, Tomonori Sato34, Reoto Takei34, Satoshi Hagimoto34, Yoichiro Noguchi34, Yasuhiko Yamano34, Hajime Sasano34, Sho Ota34, Yusuke Suzuki35, Sohei Nakayama35, Keita Masuzawa35, Takanori Asakura1,3,35, Tomomi Takano36, Kazuhiko Katayama37, Koji Murakami38, Mitsuhiro Yamada38, Hisatoshi Sugiura38, Hirohito Sano38, Shuichiro Matsumoto38, Nozomu Kimura38, Yoshinao Ono38, Hiroaki Baba39, Rie Baba40, Daisuke Arai40, Takayuki Ogura40, Hidenori Takahashi40, Shigehiro Hagiwara40, Genta Nagao40, Shunichiro Konishi40, Ichiro Nakachi40, Hiroki Tateno41, Isano Hase41, Shuichi Yoshida41, Shoji Suzuki41, Miki Kawada42, Hirohisa Horinouchi43, Fumitake Saito44, Junichi Ochi44, Keiko Mitamura45, Masao Hagihara46, Tomoyuki Uchida46, Takayuki Shiroyama47, Yuichi Maeda47, Takuro Nii47, Yoshimi Noda47, Takayuki Niitsu47, Yuichi Adachi47, Takatoshi Enomoto47, Saori Amiya47, Reina Hara47, Ryuya Edahiro47,48, Yuya Shirai47,48, Tatsuhiko Naito48, Kenichi Yamamoto48, Haruhiko Hirata47, Yoshito Takeda47, Shinichi Namba48, Ken Suzuki48, Kyuto Sonehara48,49, Noa Sasa48,50, Yuya Ueno50, Motoyuki Suzuki50, Norihiko Takemoto50, Hirotaka Eguchi50, Takahito Fukusumi50, Takao Imai50, Hidenori Inohara50, Toshihiro Kishikawa48,50,51, Shuhei Yamada51, Shuhei Kawabata51, Noriyuki Kijima51, Haruhiko Kishima51, Tomohisa Sujino52, Kaoru Takabayashi52, Naoki Hosoe52, Kazunori Tomono53, Kazuto Kato54, Munehisa Fukushima50,55, Masatoshi Takagaki51,56, Atsushi Kumanogoh47,49,56,57, Naoki Miyazawa58, Yasuhiro Kimura58, Reiko Sado58, Hideyasu Sugimoto58, Akane Kamiya59, Naota Kuwahara60, Akiko Fujiwara60, Tomohiro Matsunaga60, Yoko Sato60, Takenori Okada60, Takashi Inoue61, Toshiyuki Hirano61, Keigo Kobayashi61, Hatsuyo Takaoka61, Koichi Nishi62, Masaru Nishitsuji62, Mayuko Tani62, Junya Suzuki62, Hiroki Nakatsumi62, Hidefumi Koh63, Tadashi Manabe63, Yohei Funatsu63, Fumimaro Ito63, Takahiro Fukui63, Keisuke Shinozuka63, Sumiko Kohashi63, Masatoshi Miyazaki63, Tomohisa Shoko64, Mitsuaki Kojima64, Tomohiro Adachi64, Motonao Ishikawa65, Kenichiro Takahashi66, Kazuyoshi Watanabe67, Yoshihiro Hirai68, Hidetoshi Kawashima68, Atsuya Narita68, Kazuki Niwa69, Yoshiyuki Sekikawa69, Hisako Sageshima70, Yoshihiko Nakamura71, Kota Hoshino71, Junichi Maruyama71, Hiroyasu Ishikura71, Tohru Takata72, Takashi Ogura73, Hideya Kitamura73, Eri Hagiwara73, Kota Murohashi73, Hiroko Okabayashi73, Shigenari Nukaga74, Ryosuke Satomi74, Takao Mochimaru74,75, Yoshitaka Oyamada75, Nobuaki Mori76, Tomoya Baba77, Yasutaka Fukui77, Mitsuru Odate77, Shuko Mashimo77, Yasushi Makino77, Kazuma Yagi78, Mizuha Hashiguchi78, Junko Kagyo78, Tetsuya Shiomi78, Kodai Kawamura79, Kazuya Ichikado79, Kenta Nishiyama79, Hiroyuki Muranaka79, Kazunori Nakamura79, Satoshi Fuke80, Hiroshi Saito80, Tomoya Tsuchida81, Shigeki Fujitani82, Mumon Takita82, Daiki Morikawa82, Toru Yoshida82, Takehiro Izumo83, Minoru Inomata83, Naoyuki Kuse83, Nobuyasu Awano83, Mari Tone83, Akihiro Ito84, Toshio Odani85, Masaru Amishima86, Takeshi Hattori86, Yasuo Shichinohe87, Takashi Kagaya88, Toshiyuki Kita88, Kazuhide Ohta88, Satoru Sakagami88, Kiyoshi Koshida88, Morio Nakamura88, Koutaro Yokote89, Taka-Aki Nakada90, Ryuzo Abe90, Taku Oshima90, Tadanaga Shimada90, Kentaro Hayashi91, Tetsuo Shimizu91, Yutaka Kozu91, Hisato Hiranuma91, Yasuhiro Gon91, Namiki Izumi92, Kaoru Nagata92, Ken Ueda92, Reiko Taki92, Satoko Hanada92, Makoto Ishii93, Naozumi Hashimoto93, Keiko Wakahara93, Koji Sakamoto93, Norihito Omote93, Akira Ando93, Yu Kusaka94, Takehiko Ohba94, Susumu Isogai94, Aki Ogawa94, Takuya Inoue94, Nobuhiro Kodama95, Yasunari Kaneyama95, Shunsuke Maeda95, Takashige Kuraki96, Takemasa Matsumoto96, Masahiro Harada97, Takeshi Takahashi97, Hiroshi Ono97, Toshihiro Sakurai97, Takayuki Shibusawa97, Yusuke Kawamura98, Akiyoshi Nakayama98, Hirotaka Matsuo98, Yoshifumi Kimizuka99, Akihiko Kawana99, Tomoya Sano99, Chie Watanabe99, Ryohei Suematsu99, Makoto Masuda100, Aya Wakabayashi100, Hiroki Watanabe100, Suguru Ueda100, Masanori Nishikawa100, Ayumi Yoshifuji101, Kazuto Ito101, Saeko Takahashi102, Kota Ishioka102, Yusuke Chihara103, Mayumi Takeuchi103, Keisuke Onoi103, Jun Shinozuka103, Atsushi Sueyoshi103, Yoji Nagasaki104, Masaki Okamoto105,106, Yoshihisa Tokunaga105,106, Sayoko Ishihara107, Masatoshi Shimo107, Masafumi Watanabe108, Sumito Inoue108, Akira Igarashi108, Masamichi Sato108, Nobuyuki Hizawa109, Yoshiaki Inoue110, Shigeru Chiba111, Kunihiro Yamagata112, Hirayasu Kai112, Yuji Hiramatsu113, Satoru Fukuyama114, Keiko Kano114, Koichiro Matsumoto114, Yoshihiro Eriguchi115, Akiko Yonekawa115, Kensuke Kanaoka116, Shoichi Ihara116, Kiyoshi Komuta116, Koichiro Asano117, Tsuyoshi Oguma117, Yoko Ito117, Satoru Hashimoto118, Masaki Yamasaki118, Yu Kasamatsu119, Yuko Komase120, Naoya Hida120, Takahiro Tsuburai120, Baku Oyama120, Yuichiro Kitagawa121, Tetsuya Fukuta121, Takahito Miyake121, Shozo Yoshida121, Shinji Ogura121, Minoru Takada122, Hidenori Kanda122, Shinji Abe123, Yuta Kono123, Yuki Togashi123, Hiroyuki Takoi123, Ryota Kikuchi123, Shinichi Ogawa124, Tomouki Ogata124, Shoichiro Ishihara124, Shinji Ozaki125, Yasuko Fuchimoto125, Sae Wada125, Arihiko Kanehiro125,126, Nobukazu Fujimoto126, Kei Nishiyama127, Mariko Terashima128, Satoru Beppu128, Kosuke Yoshida128, Osamu Narumoto129, Hideaki Nagai129, Nobuharu Ooshima129, Mitsuru Motegi130, Akira Umeda131, Kazuya Miyagawa132, Hisato Shimada133, Mayu Endo134, Yoshiyuki Ohira135, Hironori Sagara135, Akihiko Tanaka135, Shin Ohta135, Tomoyuki Kimura135, Yoko Shibata136, Yoshinori Tanino136, Takefumi Nikaido136, Hiroyuki Minemura136, Yuki Sato136, Yuichiro Yamada137, Takuya Hashino137, Masato Shinoki137, Hajime Iwagoe138, Hiroshi Takahashi139, Kazuhiko Fujii139, Hiroto Kishi139, Tomoo Ishii140, Masayuki Kanai141, Tomonori Imamura141, Tatsuya Yamashita141, Masakiyo Yatomi142, Toshitaka Maeno142, Shinichi Hayashi143, Mai Takahashi143, Mizuki Kuramochi143, Isamu Kamimaki143, Yoshiteru Tominaga143, Mitsuyoshi 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Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. 2. Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan. 3. Department of Clinical Medicine (Laboratory of Bioregulatory Medicine), Kitasato University School of Pharmacy, Tokyo, Japan. 4. Department of Surgery, Keio University School of Medicine, Tokyo, Japan. 5. Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 6. Department of General Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 7. Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 7. Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 7. Department of Emergency and Disaster Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 9. Department of Internal Medicine and Rheumatology, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 10. Department of Nephrology, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan. 11. Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. 12. Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan. 13. Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan. 14. Department of Laboratory Medicine, Keio University School of Medicine, Tokyo, Japan. 15. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. 16. Keio University Health Center, Keio University School of Medicine, Tokyo, Japan. 17. Department of Integrative Medicine and Biochemistry, Keio University School of Medicine, Tokyo, Japan. 18. Department of Respiratory Medicine, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan. 19. Department of Infection Control, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan. 20. JCHO (Japan Community Health Care Organization) Saitama Medical Center, Internal Medicine, Saitama, Japan. 21. Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Saitama, Japan. 22. Department of Respiratory Medicine, Tokyo Women's Medical University, Tokyo, Japan. 23. Department of General Medicine, Tokyo Women's Medical University, Tokyo, Japan. 24. Department of Emergency and Critical Care Medicine, Kansai Medical University General Medical Center, Osaka, Japan. 25. M&D Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan. 26. Clinical Research Center, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan. 27. Department of Medical Informatics, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan. 28. Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 29. Clinical Laboratory, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan. 30. Department of Insured Medical Care Management, Tokyo Medical and Dental University Hospital of Medicine, Tokyo, Japan. 31. Fukujuji Hospital, Tokyo, Japan. 32. Kawasaki Municipal Ida Hospital, Department of Internal Medicine, Kanagawa, Japan. 33. Department of Infectious Diseases, Tosei General Hospital, Aichi, Japan. 34. Department of Respiratory Medicine and Allergy, Tosei General Hospital, Aichi, Japan. 35. Department of Respiratory Medicine, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. 36. School of Veterinary Medicine, Kitasato University, Aomori, Japan. 37. Laboratory of Viral Infection I, Department of Infection Control and Immunology, Ōmura Satoshi Memorial Institute & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan. 38. Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan. 39. Department of Infectious Diseases, Tohoku University Graduate School of Medicine, Miyagi, Japan. 40. Saiseikai Utsunomiya Hospital, Tochigi, Japan. 41. Department of Pulmonary Medicine, Saitama City Hospital, Saitama, Japan. 42. Department of Infectious Diseases, Saitama City Hospital, Saitama, Japan. 43. Department of General Thoracic Surgery, Saitama City Hospital, Saitama, Japan. 44. Department of Pulmonary Medicine, Eiju General Hospital, Tokyo, Japan. 45. Division of Infection Control, Eiju General Hospital, Tokyo, Japan. 46. Department of Hematology, Eiju General Hospital, Tokyo, Japan. 47. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. 48. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan. 49. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan. 50. Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. 51. Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan. 52. Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan. 53. Division of Infection Control and Prevention, Osaka University Hospital, Osaka, Japan. 54. Department of Biomedical Ethics and Public Policy, Osaka University Graduate School of Medicine, Osaka, Japan. 55. Department of Otolaryngology and Head and Neck Surgery, Kansai Rosai Hospital, Hyogo, Japan. 56. Department of Immunopathology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan. 57. The Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, Japan. 58. Department of Respirtory Medicine, Saiseikai Yokohamashi Nanbu Hospital, Kanagawa, Japan. 59. Department of Clinical Laboratory, Saiseikai Yokohamashi Nanbu Hospital, Kanagawa, Japan. 60. Internal Medicine, Internal Medicine Center, Showa University Koto Toyosu Hospital, Tokyo, Japan. 61. Internal Medicine, Sano Kosei General Hospital, Tochigi, Japan. 62. Ishikawa Prefectural Central Hospital, Ishikawa, Japan. 63. Tachikawa Hospital, Tokyo, Japan. 64. Department of Emergency and Critical Care Medicine, Tokyo Women's Medical University Medical Center East, Tokyo, Japan. 65. Department of Medicine, Tokyo Women's Medical University Medical Center East, Tokyo, Japan. 66. Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan. 67. Japan Community Health care Organization Kanazawa Hospital, Ishikawa, Japan. 68. Department of Respiratory Medicine, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan. 69. Department of Generai Internal Medicine, Japan Organization of Occupational Health and Safety, Kanto Rosai Hospital, Kanagawa, Japan. 70. Sapporo City General Hospital, Hokkaido, Japan. 71. Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. 72. Department of Infection Control, Fukuoka University Hospital, Fukuoka, Japan. 73. Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan. 74. Department of Respiratory Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 75. Department of Allergy, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 76. Department of General Internal Medicine and Infectious Diseases, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 77. Department of Respiratory Medicine, Toyohashi Municipal Hospital, Aichi, Japan. 78. Keiyu Hospital, Kanagawa, Japan. 79. Division of Respiratory Medicine, Social Welfare Organization Saiseikai Imperial Gift Foundation, Inc., Saiseikai Kumamoto Hospital, Kumamoto, Japan. 80. KKR Sapporo Medical Center, Department of respiratory medicine, Hokkaido, Japan. 81. Division of General Internal Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan. 82. Departmet of Emergency and Critical Care Medicine, St. Marianna University School of Medicine, Kanagawa, Japan. 83. Japanese Red Cross Medical Center, Tokyo, Japan. 84. Matsumoto City Hostpital, Nagano, Japan. 85. Department of Rheumatology, National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan. 86. Department of Respiratory Medicine, National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan. 87. Department of Emergency and Critical Care Medicine, National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan. 88. NHO Kanazawa Medical Center, Ishikawa, Japan. 89. Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. 90. Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. 91. Nihon University School of Medicine, Department of Internal Medicine, Division of Respiratory Medicine, Tokyo, Japan. 92. Musashino Red Cross Hospital, Tokyo, Japan. 93. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan. 94. Ome Municipal General Hospital, Tokyo, Japan. 95. Fukuoka Tokushukai Hospital, Department of Internal Medicine, Fukuoka, Japan. 96. Fukuoka Tokushukai Hospital, Respiratory Medicine, Fukuoka, Japan. 97. National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan. 98. Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan. 99. Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan. 100. Department of Respiratory Medicine, Fujisawa City Hospital, Kanagawa, Japan. 101. Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan. 102. Department of Pulmonary Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan. 103. Uji-Tokushukai Medical Center, Kyoto, Japan. 104. Department of Infectious Disease and Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka Japan. 105. Department of Respirology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 106. Division of Respirology, Rheumatology, and Neurology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. 107. Department of Infectious Disease, National Hospital Organization Kyushu Medical Center, Fukuoka Japan. 108. Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Faculty of Medicine, Yamagata, Japan. 109. Department of Pulmonary Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. 110. Department of Emergency and Critical Care Medicine, Facualty of Medicine, University of Tsukuba, Ibaraki, Japan. 111. Departmentof Hematology, Facualty of Medicine, University of Tsukuba, Ibaraki, Japan. 112. Department of Nephrology, Facualty of Medicine, University of Tsukuba, Ibaraki, Japan. 113. Department of Cardiovascular Surgery, Facualty of Medicine, University of Tsukuba, Ibaraki, Japan. 114. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 115. Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. 116. Daini Osaka Police Hospital, Osaka, Japan. 117. Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan. 118. Department of Anesthesiology and Intensive Care Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 119. Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 120. Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama-City Seibu Hospital, Kanagawa, Japan. 121. Gifu University School of Medicine Graduate School of Medicine, Emergency and Disaster Medicine, Gifu, Japan. 122. KINSHUKAI Hanwa The Second Hospital, Osaka, Japan. 123. Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan. 124. JA Toride medical hospital, Ibaraki, Japan. 125. Okayama Rosai Hospital, Okayama, Japan. 126. Himeji St. Mary's Hospital, Hyogo, Japan. 127. Emergency & Critical Care, Niigata University, Niigata, Japan. 128. Emergency & Critical Care Center, National Hospital Organization Kyoto Medical Center, Kyoto, Japan. 129. National Hospital Organization Tokyo National Hospital, Tokyo, Japan. 130. Fujioka General Hospital, Gumma, Japan. 131. Department of General Medicine, School of Medicine, International University of Health and Welfare Shioya Hospital, Tochigi, Japan. 132. Department of Pharmacology, School of Pharmacy, International University of Health and Welfare Shioya Hospital, Tochigi, Japan. 133.Department of Respiratory Medicine, International University of Health and Welfare Shioya Hospital, Tochigi, Japan. 134.Department of Clinical Laboratory, International University of Health and Welfare Shioya Hospital, Tochigi, Japan. 135.Department of General Medicine, School of Medicine, International University of Health and Welfare, Chiba, Japan. 136. Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan. 137. Kansai Electric Power Hospital, Osaka, Japan. 138. Department of Infectious Diseases, Kumamoto City Hospital, Kumamoto, Japan. 139. Department of Respiratory Medicine, Kumamoto City Hospital, Kumamoto, Japan. 140. Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan. 141. Department of Emergency and Critical Care Medicine, Tokyo Metropolitan Police Hospital, Tokyo, Japan. 142. Department of Respiratory Medicine, Gunma University Graduate School of Medicine, Gumma, Japan. 143. National hospital organization Saitama Hospital, Saitama, Japan. 144. Department of Internal Medicine, Kiryu Kosei General Hospital, Gumma, Japan. 145. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. 146. Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. 147. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan. 148. Division of Health Medical Intelligence, Human Genome Center, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan. 149. Department of Neurosurgery, Faculty of Medicine, the University of Tokyo, Tokyo, Japan. 150. Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. 151. Genome Medical Science Project (Toyama), National Center for Global Health and Medicine, Tokyo, Japan. 152. Department of Biomolecular Engineering, Graduate School of Tokyo Institute of Technology, Tokyo, Japan. 153. Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 154. Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan. 155. Health Science Research and Development Center (HeRD), Tokyo Medical and Dental University, Tokyo, Japan. 156. Institute of Research, Tokyo Medical and Dental University, Tokyo, Japan.

Funding

This study was supported by the Japan Agency for Medical Research and Development (AMED, JP20nk0101612, JP20fk0108415, JP21jk0210034, JP21km0405211 and JP21km0405217), the Japan Science and Technology Agency (JST CREST, JPMJCR20H2; JST PRESTO; JPMJPR21R7), the Ministry of Health, Labour and Welfare (MHLW, 20CA2054), the Takeda Science Foundation, the Mitsubishi Foundation, and the Bioinformatics Initiative of Osaka University Graduate School of Medicine, Osaka University.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan

    Yuta Matsubara, Hiroki Kiyohara, Yohei Mikami, Kosaku Nanki, Shinya Sugimoto, Yusuke Yoshimatsu & Takanori Kanai

  2. Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan

    Ho Namkoong & Naoki Hasegawa

  3. Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Shotaro Chubachi, Hiromu Tanaka, Shuhei Azekawa & Koichi Fukunaga

  4. Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan

    Tomohisa Sujino, Kaoru Takabayashi & Naoki Hosoe

  5. Department of Integrative Medicine and Biochemistry, Keio University School of Medicine, Tokyo, Japan

    Toshiro Sato

  6. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan

    Makoto Ishii & Atsuya Narita

  7. Department of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Yukinori Okada

  8. Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan

    Yukinori Okada

  9. Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan

    Yukinori Okada

  10. Health Science Research and Development Center (HeRD), Tokyo Medical and Dental University, Tokyo, Japan

    Ryuji Koike

  11. Department of Surgery, Keio University School of Medicine, Tokyo, Japan

    Yuko Kitagawa

  12. Institute of Research, Tokyo Medical and Dental University, Tokyo, Japan

    Akinori Kimura

  13. Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Seiya Imoto

  14. M&D Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan

    Satoru Miyano

  15. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan

    Seishi Ogawa

Authors
  1. Yuta Matsubara
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  2. Hiroki Kiyohara
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  3. Yohei Mikami
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  4. Kosaku Nanki
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  5. Ho Namkoong
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  6. Shotaro Chubachi
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  7. Hiromu Tanaka
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  8. Shuhei Azekawa
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  9. Shinya Sugimoto
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  10. Yusuke Yoshimatsu
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  11. Tomohisa Sujino
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  12. Kaoru Takabayashi
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  13. Naoki Hosoe
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  14. Toshiro Sato
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  15. Makoto Ishii
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  16. Naoki Hasegawa
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  17. Yukinori Okada
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  18. Ryuji Koike
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  19. Yuko Kitagawa
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  20. Akinori Kimura
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  21. Seiya Imoto
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  22. Satoru Miyano
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  23. Seishi Ogawa
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  24. Koichi Fukunaga
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  25. Takanori Kanai
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Consortia

The Japan COVID-19 Task Force

  • Shotaro Chubachi
  • , Ho Namkoong
  • , Takahiro Fukushima
  • , Hiromu Tanaka
  • , Ho Lee
  • , Shiro Otake
  • , Kensuke Nakagawara
  • , Atsuho Morita
  • , Mayuko Watase
  • , Kaori Sakurai
  • , Takunori Ogawa
  • , Takuya Kusumoto
  • , Katsunori Masaki
  • , Hiroki Kabata
  • , Shinnosuke Ikemura
  • , Satoshi Okamori
  • , Hideki Terai
  • , Hirofumi Kamata
  • , Sho Uchida
  • , Shunsuke Uno
  • , Naoki Hasegawa
  • , Kazuhisa Takahashi
  • , Hitoshi Sasano
  • , Yuko Kitagawa
  • , Norihiro Harada
  • , Haruhi Takagi
  • , Ai Nakamura
  • , Toshio Naito
  • , Makoto Hiki
  • , Yasushi Matsushita
  • , Ryousuke Aoki
  • , Sonoko Harada
  • , Junichi Sasaki
  • , Hiroshi Morisaki
  • , Yoshifumi Uwamino
  • , Kosaku Nanki
  • , Yohei Mikami
  • , Rino Ishihara
  • , Yuta Matsubara
  • , Hiroki Kiyohara
  • , Shinya Sugimoto
  • , Yusuke Yoshimatsu
  • , Tomoyasu Nishimura
  • , Toshiro Sato
  • , Tetsuya Ueda
  • , Masanori Azuma
  • , Ryuichi Saito
  • , Toshikatsu Sado
  • , Yoshimune Miyazaki
  • , Ryuichi Sato
  • , Yuki Haruta
  • , Tadao Nagasaki
  • , Yoshinori Hasegawa
  • , Yoshinori Yasui
  • , Soichiro Ueda
  • , Ai Tada
  • , Masayoshi Miyawaki
  • , Masaomi Yamamoto
  • , Eriko Yoshida
  • , Reina Hayashi
  • , Tomoki Nagasaka
  • , Sawako Arai
  • , Yutaro Kaneko
  • , Kana Sasaki
  • , Takashi Ishiguro
  • , Taisuke Isono
  • , Shun Shibata
  • , Yuma Matsui
  • , Chiaki Hosoda
  • , Kenji Takano
  • , Takashi Nishida
  • , Yoichi Kobayashi
  • , Yotaro Takaku
  • , Noboru Takayanagi
  • , Etsuko Tagaya
  • , Ken Arimura
  • , Masatoshi Kawana
  • , Yasushi Nakamori
  • , Kazuhisa Yoshiya
  • , Fukuki Saito
  • , Tomoyuki Yoshihara
  • , Daiki Wada
  • , Hiromu Iwamura
  • , Syuji Kanayama
  • , Shuhei Maruyama
  • , Takanori Hasegawa
  • , Kunihiko Takahashi
  • , Tatsuhiko Anzai
  • , Satoshi Ito
  • , Akifumi Endo
  • , Yuji Uchimura
  • , Yasunari Miyazaki
  • , Takayuki Honda
  • , Tomoya Tateishi
  • , Shuji Tohda
  • , Naoya Ichimura
  • , Kazunari Sonobe
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  • , Jun Nakajima
  • , Masumi Ai
  • , Takashi Yoshiyama
  • , Ken Ohta
  • , Hiroyuki Kokuto
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  • , Ryusuke Anan
  • , Ryosuke Arai
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  • , Yuko Harada
  • , Kazumi Nishio
  • , Yoshikazu Mutoh
  • , Tomonori Sato
  • , Reoto Takei
  • , Satoshi Hagimoto
  • , Yoichiro Noguchi
  • , Yasuhiko Yamano
  • , Hajime Sasano
  • , Sho Ota
  • , Yusuke Suzuki
  • , Sohei Nakayama
  • , Keita Masuzawa
  • , Takanori Asakura
  • , Tomomi Takano
  • , Kazuhiko Katayama
  • , Koji Murakami
  • , Mitsuhiro Yamada
  • , Hisatoshi Sugiura
  • , Hirohito Sano
  • , Shuichiro Matsumoto
  • , Nozomu Kimura
  • , Yoshinao Ono
  • , Hiroaki Baba
  • , Rie Baba
  • , Daisuke Arai
  • , Takayuki Ogura
  • , Hidenori Takahashi
  • , Shigehiro Hagiwara
  • , Genta Nagao
  • , Shunichiro Konishi
  • , Ichiro Nakachi
  • , Hiroki Tateno
  • , Isano Hase
  • , Shuichi Yoshida
  • , Shoji Suzuki
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  • , Kazunori Tomono
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  • , Mayuko Tani
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  • , Hiroki Nakatsumi
  • , 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
  • , Kazuyoshi Watanabe
  • , Yoshihiro Hirai
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  • , Atsuya Narita
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  • , Kota Hoshino
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  • , Tohru Takata
  • , Takashi Ogura
  • , Hideya Kitamura
  • , Eri Hagiwara
  • , Kota Murohashi
  • , Hiroko Okabayashi
  • , Shigenari Nukaga
  • , Ryosuke Satomi
  • , Takao Mochimaru
  • , Yoshitaka Oyamada
  • , Nobuaki Mori
  • , Tomoya Baba
  • , Yasutaka Fukui
  • , Mitsuru Odate
  • , Shuko Mashimo
  • , Yasushi Makino
  • , Kazuma Yagi
  • , Mizuha Hashiguchi
  • , Junko Kagyo
  • , Tetsuya Shiomi
  • , Kodai Kawamura
  • , Kazuya Ichikado
  • , Kenta Nishiyama
  • , Hiroyuki Muranaka
  • , Kazunori Nakamura
  • , 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
  • , Toshio Odani
  • , Masaru Amishima
  • , Takeshi Hattori
  • , Yasuo Shichinohe
  • , Takashi Kagaya
  • , Toshiyuki Kita
  • , Kazuhide Ohta
  • , Satoru Sakagami
  • , Kiyoshi Koshida
  • , Morio Nakamura
  • , Koutaro Yokote
  • , Taka-Aki Nakada
  • , Ryuzo Abe
  • , Taku Oshima
  • , Tadanaga Shimada
  • , Kentaro Hayashi
  • , Tetsuo Shimizu
  • , Yutaka Kozu
  • , Hisato Hiranuma
  • , Yasuhiro Gon
  • , Namiki Izumi
  • , Kaoru Nagata
  • , Ken Ueda
  • , Reiko Taki
  • , Satoko Hanada
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  • , Koji Sakamoto
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  • , Takehiko Ohba
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  • , Aki Ogawa
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  • , Hiroshi Ono
  • , Toshihiro Sakurai
  • , Takayuki Shibusawa
  • , Yusuke Kawamura
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  • , Yoshifumi Kimizuka
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  • , Tomoya Sano
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  • , Yuta Kono
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  • , Hiroyuki Takoi
  • , Ryota Kikuchi
  • , Shinichi Ogawa
  • , Tomouki Ogata
  • , Shoichiro Ishihara
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  • , Yasuko Fuchimoto
  • , Sae Wada
  • , Arihiko Kanehiro
  • , 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
  • , 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
  • , Tomoo Ishii
  • , Masayuki Kanai
  • , Tomonori Imamura
  • , Tatsuya Yamashita
  • , Masakiyo Yatomi
  • , Toshitaka Maeno
  • , Shinichi Hayashi
  • , Mai Takahashi
  • , Mizuki Kuramochi
  • , Isamu Kamimaki
  • , Yoshiteru Tominaga
  • , Mitsuyoshi Utsugi
  • , Akihiro Ono
  • , Toru Tanaka
  • , Takeru Kashiwada
  • , Kazue Fujita
  • , Yoshinobu Saito
  • , Masahiro Seike
  • , Masahiro Kanai
  • , Ryunosuke Saiki
  • , Yasuhito Nannya
  • , Takayoshi Hyugaji
  • , Eigo Shimizu
  • , Kotoe Katayama
  • , Seiya Imoto
  • , Satoru Miyawaki
  • , Meiko Takahashi
  • , Fumihiko Matsuda
  • , Yosuke Omae
  • , Katsushi Tokunaga
  • , Takafumi Ueno
  • , Yukinori Okada
  • , Ryuji Koike
  • , Akinori Kimura
  • , Satoru Miyano
  • , Seishi Ogawa
  • , Koichi Fukunaga
  •  & Takanori Kanai

Contributions

Conceptualization: Y. Matsubara, H. Kiyohara, Y. Mikami, and T. Kanai. Data curation: Y. Matsubara, H. Kiyohara, Y. Mikami, K. Nanki, S. Chubachi, H. Namkoong, and H. Kamata. Formal analysis: Y. Matsubara and H. Kiyohara. Funding acquisition: K. Fukunaga, T. Kanai, S. Imoto, H. Namkoong, and Y. Okada. Investigation: Y. Matsubara, H. Kiyohara, Y. Mikami, K. Nanki, S. Chubachi, H. Namkoong, H. Kamata, N. Hasegawa, Y. Okada, R. Koike, Y. Kitagawa, A. Kimura, S. Imoto, S. Miyano, S. Ogawa, and K. Fukunaga. Methodology: Y. Matsubara, H. Kiyohara, S. Sugimoto, Y. Yoshimatsu, T. Sujino, K. Takabayashi, N. Hosoe, and T. Kanai. Project administration: K. Fukunaga and T. Kanai. Resources: Y. Kitagawa, A. Kimura, S. Imoto, S. Miyano, S. Ogawa, and K. Fukunaga. Software: S. Chubachi and H. Namkoong, and Y. Okada. Supervision: K. Fukunaga and T. Kanai. Validation: Y. Matsubara and H. Kiyohara. Visualization: Y. Matsubara and H. Kiyohara. Writing original draft: Y. Matsubara and H. Kiyohara. Review and editing: All authors. The final version of this manuscript was approved by all the authors.

Corresponding author

Correspondence to Hiroki Kiyohara.

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Conflict of interest

S. Ogawa is a board member of Chordia Therapeutics Inc. and Eisai Co., Ltd., and he received research grants from Eisai Co., Ltd., Chordia Therapeutics Inc., and Otsuka Pharmaceutical Co., Ltd. S. Ogawa also owns stocks of Asahi Genomics Inc., and he is affiliated with the endowed chair from Chordia Therapeutics Inc. and Nanpuh Hospital.

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Matsubara, Y., Kiyohara, H., Mikami, Y. et al. Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study. J Gastroenterol 59, 195–208 (2024). https://doi.org/10.1007/s00535-023-02071-x

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