Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity
Authors: Edahiro Ryuya , Shirai Yuya , Takeshima Yusuke , Sakakibara Shuhei , Yamaguchi Yuta , Murakami Teruaki , Morita Takayoshi , Kato Yasuhiro , Liu Yu-Chen , Motooka Daisuke , Naito Yoko , Takuwa Ayako , Sugihara Fuminori , Tanaka Kentaro , Wing James B. , Sonehara Kyuto , Tomofuji Yoshihiko ,   Japan COVID-19 Task Force, Wang Qingbo S. , Hasegawa Takanori , Saiki Ryunosuke , Hyugaji Takayoshi , Shimizu Eigo , Katayama Kotoe , Kanai Masahiro , Naito Tatsuhiko , Sasa Noah , Yamamoto Kenichi , Takahashi Kazuhisa , Harada Norihiro , Naito Toshio , Hiki Makoto , Matsushita Yasushi , Takagi Haruhi , Ichikawa Masako , Nakamura Ai , Harada Sonoko , Sandhu Yuuki , Kabata Hiroki , Masaki Katsunori , Kamata Hirofumi , Ikemura Shinnosuke , Chubachi Shotaro , Okamori Satoshi , Terai Hideki , Morita Atsuho , Asakura Takanori , Sasaki Junichi , Morisaki Hiroshi , Uwamino Yoshifumi , Nanki Kosaku , Uchida Sho , Uno Shunsuke , Nishimura Tomoyasu , Ishiguro Takashi , Isono Taisuke , Shibata Shun , Matsui Yuma , Hosoda Chiaki , Takano Kenji , Nishida Takashi , Kobayashi Yoichi , Takaku Yotaro , Takayanagi Noboru , Ueda Soichiro , Tada Ai , Miyawaki Masayoshi , Yamamoto Masaomi , Yoshida Eriko , Hayashi Reina , Nagasaka Tomoki , Arai Sawako , Kaneko Yutaro , Sasaki Kana , Tagaya Etsuko , Kawana Masatoshi , Arimura Ken , Takahashi Kunihiko , Anzai Tatsuhiko , Ito Satoshi , Endo Akifumi , Uchimura Yuji , Miyazaki Yasunari , Honda Takayuki , Tateishi Tomoya , Tohda Shuji , Ichimura Naoya , Sonobe Kazunari , Sassa Chihiro Tani , Nakajima Jun , Nakano Yasushi , Nakajima Yukiko , Anan Ryusuke , Arai Ryosuke , Kurihara Yuko , Harada Yuko , Nishio Kazumi , Ueda Tetsuya , Azuma Masanori , Saito Ryuichi , Sado Toshikatsu , Miyazaki Yoshimune , Sato Ryuichi , Haruta Yuki , Nagasaki Tadao , Yasui Yoshinori , Hasegawa Yoshinori , Mutoh Yoshikazu , Kimura Tomoki , Sato Tomonori , Takei Reoto , Hagimoto Satoshi , Noguchi Yoichiro , Yamano Yasuhiko , Sasano Hajime , Ota Sho , Nakamori Yasushi , Yoshiya Kazuhisa , Saito Fukuki , Yoshihara Tomoyuki , Wada Daiki , Iwamura Hiromu , Kanayama Syuji , Maruyama Shuhei , Yoshiyama Takashi , Ohta Ken , Kokuto Hiroyuki , Ogata Hideo , Tanaka Yoshiaki , Arakawa Kenichi , Shimoda Masafumi , Osawa Takeshi , Tateno Hiroki , Hase Isano , Yoshida Shuichi , Suzuki Shoji , Kawada Miki , Horinouchi Hirohisa , Saito Fumitake , Mitamura Keiko , Hagihara Masao , Ochi Junichi , Uchida Tomoyuki , Baba Rie , Arai Daisuke , Ogura Takayuki , Takahashi Hidenori , Hagiwara Shigehiro , Nagao Genta , Konishi Shunichiro , Nakachi Ichiro , Murakami Koji , Yamada Mitsuhiro , Sugiura Hisatoshi , Sano Hirohito , Matsumoto Shuichiro , Kimura Nozomu , Ono Yoshinao , Baba Hiroaki , Suzuki Yusuke , Nakayama Sohei , Masuzawa Keita , Namba Shinichi , Shiroyama Takayuki , Noda Yoshimi , Niitsu Takayuki , Adachi Yuichi , Enomoto Takatoshi , Amiya Saori , Hara Reina , Kuge Tomoki , Matsumoto Kinnosuke , Yamamoto Yuji , Yamamoto Makoto , Yoneda Midori , Tomono Kazunori , Kato Kazuto , Koh Hidefumi , Manabe Tadashi , Funatsu Yohei , Ito Fumimaro , Fukui Takahiro , Shinozuka Keisuke , Kohashi Sumiko , Miyazaki Masatoshi , Shoko Tomohisa , Kojima Mitsuaki , Adachi Tomohiro , Ishikawa Motonao , Takahashi Kenichiro , Inoue Takashi , Hirano Toshiyuki , Kobayashi Keigo , Takaoka Hatsuyo , Watanabe Kazuyoshi , Miyazawa Naoki , Kimura Yasuhiro , Sado Reiko , Sugimoto Hideyasu , Kamiya Akane , Kuwahara Naota , Fujiwara Akiko , Matsunaga Tomohiro , Sato Yoko , Okada Takenori , Hirai Yoshihiro , Kawashima Hidetoshi , Narita Atsuya , Niwa Kazuki , Sekikawa Yoshiyuki , Nishi Koichi , Nishitsuji Masaru , Tani Mayuko , Suzuki Junya , Nakatsumi Hiroki , Ogura Takashi , Kitamura Hideya , Hagiwara Eri , Murohashi Kota , Okabayashi Hiroko , Mochimaru Takao , Nukaga Shigenari , Satomi Ryosuke , Oyamada Yoshitaka , Mori Nobuaki , Baba Tomoya , Fukui Yasutaka , Odate Mitsuru , Mashimo Shuko , Makino Yasushi , Yagi Kazuma , Hashiguchi Mizuha , Kagyo Junko , Shiomi Tetsuya , Fuke Satoshi , Saito Hiroshi , Tsuchida Tomoya , Fujitani Shigeki , Takita Mumon , Morikawa Daiki , Yoshida Toru , Izumo Takehiro , Inomata Minoru , Kuse Naoyuki , Awano Nobuyasu , Tone Mari , Ito Akihiro , Nakamura Yoshihiko , Hoshino Kota , Maruyama Junichi , Ishikura Hiroyasu , Takata Tohru , Odani Toshio , Amishima Masaru , Hattori Takeshi , Shichinohe Yasuo , Kagaya Takashi , Kita Toshiyuki , Ohta Kazuhide , Sakagami Satoru , Koshida Kiyoshi , Hayashi Kentaro , Shimizu Tetsuo , Kozu Yutaka , Hiranuma Hisato , Gon Yasuhiro , Izumi Namiki , Nagata Kaoru , Ueda Ken , Taki Reiko , Hanada Satoko , Kawamura Kodai , Ichikado Kazuya , Nishiyama Kenta , Muranaka Hiroyuki , Nakamura Kazunori , Hashimoto Naozumi , Wakahara Keiko , Koji Sakamoto , Omote Norihito , Ando Akira , Kodama Nobuhiro , Kaneyama Yasunari , Maeda Shunsuke , Kuraki Takashige , Matsumoto Takemasa , Yokote Koutaro , Nakada Taka-Aki , Abe Ryuzo , Oshima Taku , Shimada Tadanaga , Harada Masahiro , Takahashi Takeshi , Ono Hiroshi , Sakurai Toshihiro , Shibusawa Takayuki , Kimizuka Yoshifumi , Kawana Akihiko , Sano Tomoya , Watanabe Chie , Suematsu Ryohei , Sageshima Hisako , Yoshifuji Ayumi , Ito Kazuto , Takahashi Saeko , Ishioka Kota , Nakamura Morio , Masuda Makoto , Wakabayashi Aya , Watanabe Hiroki , Ueda Suguru , Nishikawa Masanori , Chihara Yusuke , Takeuchi Mayumi , Onoi Keisuke , Shinozuka Jun , Sueyoshi Atsushi , Nagasaki Yoji , Okamoto Masaki , Ishihara Sayoko , Shimo Masatoshi , Tokunaga Yoshihisa , Kusaka Yu , Ohba Takehiko , Isogai Susumu , Ogawa Aki , Inoue Takuya , Fukuyama Satoru , Eriguchi Yoshihiro , Yonekawa Akiko , Kan-o Keiko , Matsumoto Koichiro , Kanaoka Kensuke , Ihara Shoichi , Komuta Kiyoshi , Inoue Yoshiaki , Chiba Shigeru , Yamagata Kunihiro , Hiramatsu Yuji , Kai Hirayasu , Asano Koichiro , Oguma Tsuyoshi , Ito Yoko , Hashimoto Satoru , Yamasaki Masaki , Kasamatsu Yu , Komase Yuko , Hida Naoya , Tsuburai Takahiro , Oyama Baku , Takada Minoru , Kanda Hidenori , Kitagawa Yuichiro , Fukuta Tetsuya , Miyake Takahito , Yoshida Shozo , Ogura Shinji , Abe Shinji , Kono Yuta , Togashi Yuki , Takoi Hiroyuki , Kikuchi Ryota , Ogawa Shinichi , Ogata Tomouki , Ishihara Shoichiro , Kanehiro Arihiko , Ozaki Shinji , Fuchimoto Yasuko , Wada Sae , Fujimoto Nobukazu , Nishiyama Kei , Terashima Mariko , Beppu Satoru , Yoshida Kosuke , Narumoto Osamu , Nagai Hideaki , Ooshima Nobuharu , Motegi Mitsuru , Umeda Akira , Miyagawa Kazuya , Shimada Hisato , Endo Mayu , Ohira Yoshiyuki , Watanabe Masafumi , Inoue Sumito , Igarashi Akira , Sato Masamichi , Sagara Hironori , Tanaka Akihiko , Ohta Shin , Kimura Tomoyuki , Shibata Yoko , Tanino Yoshinori , Nikaido Takefumi , Minemura Hiroyuki , Sato Yuki , Yamada Yuichiro , Hashino Takuya , Shinoki Masato , Iwagoe Hajime , Takahashi Hiroshi , Fujii Kazuhiko , Kishi Hiroto , Kanai Masayuki , Imamura Tomonori , Yamashita Tatsuya , Yatomi Masakiyo , Maeno Toshitaka , Hayashi Shinichi , Takahashi Mai , Kuramochi Mizuki , Kamimaki Isamu , Tominaga Yoshiteru , Ishii Tomoo , Utsugi Mitsuyoshi , Ono Akihiro , Tanaka Toru , Kashiwada Takeru , Fujita Kazue , Saito Yoshinobu , Seike Masahiro , Watanabe Hiroko , Matsuse Hiroto , Kodaka Norio , Nakano Chihiro , Oshio Takeshi , Hirouchi Takatomo , Makino Shohei , Egi Moritoki , Omae Yosuke , Nannya Yasuhito , Ueno Takafumi , Takano Tomomi , Katayama Kazuhiko , Ai Masumi , Sato Toshiro , Hasegawa Naoki , Tokunaga Katsushi , Ishii Makoto , Koike Ryuji , Kitagawa Yuko , Kimura Akinori , Imoto Seiya , Miyano Satoru , Ogawa Seishi , Kanai Takanori , Namkoong Ho , Tanaka Hiromu , Lee Ho , Fukunaga Koichi , Hirata Haruhiko , Takeda Yoshito , Okuzaki Daisuke , Kumanogoh Atsushi , Okada Yukinori 
Published: April 2023

Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.