t6A and ms2t6A 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

doi:10.3390/biom12091233

t⁶A and ms²t⁶A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity

Biomolecules. 2022 Sep 3;12(9):1233. doi: 10.3390/biom12091233.

Authors

Yu Nagayoshi^{1

2}, Kayo Nishiguchi¹, Ryosuke Yamamura^{1

2}, Takeshi Chujo¹, Hiroyuki Oshiumi³, Hiroko Nagata¹, Hitomi Kaneko¹, Keiichi Yamamoto⁴, Hirotomo Nakata⁵, Korin Sakakida^{1

6}, Akihiro Kunisawa⁷, Masataka Adachi², Yutaka Kakizoe², Takanori Mizobe⁸, Jun-Ichi Kuratsu⁹, Shinya Shimada¹⁰, Yasushi Nakamori¹¹, Masao Matsuoka⁵, Masashi Mukoyama², Fan-Yan Wei¹², Kazuhito Tomizawa¹

Affiliations

¹ Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
² Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
³ Department of Immunology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
⁴ Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto 860-8556, Japan.
⁵ Department of Hematology, Rheumatology and Infectious Diseases, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
⁶ Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
⁷ Shimadzu Corporation, Kyoto 604-8442, Japan.
⁸ Kumamoto Kenhoku Hospital, Kumamoto 865-8005, Japan.
⁹ Sakurajyuji Hospital, Kumamoto 861-4173, Japan.
¹⁰ JCHO Kumamoto General Hospital, Kumamoto 866-8660, Japan.
¹¹ Department of Emergency and Critical Care Medicine, Kansai Medical University General Medical Center, Osaka 570-8507, Japan.
¹² Department of Modomics Biology and Medicine, Institute of Development Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.

Abstract

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.

Keywords: COVID-19; LC-MS; modified nucleosides.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / analogs & derivatives
Biomarkers
COVID-19* / diagnosis
Humans
Nucleosides* / chemistry
RNA
SARS-CoV-2
Threonine / analogs & derivatives

Substances

2-methylthio-N6-threonylcarbamoyladenosine
Biomarkers
Nucleosides
N(6)-(N-threonylcarbonyl)adenosine
Threonine
RNA
Adenosine

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This study was supported by grants from the Cooperative Research Project Program of Joint Usage/Research Center at the Institute of Development, Aging and Cancer, Tohoku University, and AMABIE Research Project, Kumamoto University.