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
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.