t<sup>6</sup>A and ms<sup>2</sup>t<sup>6</sup>A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity
Yu Nagayoshi,
Kayo Nishiguchi,
Ryosuke Yamamura,
Takeshi Chujo,
Hiroyuki Oshiumi,
Hiroko Nagata,
Hitomi Kaneko,
Keiichi Yamamoto,
Hirotomo Nakata,
Korin Sakakida,
Akihiro Kunisawa,
Masataka Adachi,
Yutaka Kakizoe,
Takanori Mizobe,
Jun-ichi Kuratsu,
Shinya Shimada,
Yasushi Nakamori,
Masao Matsuoka,
Masashi Mukoyama,
Fan-Yan Wei,
Kazuhito Tomizawa
Affiliations
Yu Nagayoshi
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Kayo Nishiguchi
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Ryosuke Yamamura
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Takeshi Chujo
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Hiroyuki Oshiumi
Department of Immunology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Hiroko Nagata
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Hitomi Kaneko
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Keiichi Yamamoto
Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto 860-8556, Japan
Hirotomo Nakata
Department of Hematology, Rheumatology and Infectious Diseases, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Korin Sakakida
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Akihiro Kunisawa
Shimadzu Corporation, Kyoto 604-8442, Japan
Masataka Adachi
Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Yutaka Kakizoe
Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Takanori Mizobe
Kumamoto Kenhoku Hospital, Kumamoto 865-8005, Japan
Jun-ichi Kuratsu
Sakurajyuji Hospital, Kumamoto 861-4173, Japan
Shinya Shimada
JCHO Kumamoto General Hospital, Kumamoto 866-8660, Japan
Yasushi Nakamori
Department of Emergency and Critical Care Medicine, Kansai Medical University General Medical Center, Osaka 570-8507, Japan
Masao Matsuoka
Department of Hematology, Rheumatology and Infectious Diseases, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Masashi Mukoyama
Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Fan-Yan Wei
Department of Modomics Biology and Medicine, Institute of Development Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
Kazuhito Tomizawa
Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N6-threonylcarbamoyladenosine (t6A) and 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity.
