{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:23:01Z","timestamp":1775625781646,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Emerging and re-emerging respiratory viruses can spread rapidly and cause pandemics as demonstrated by the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The early human immune responses to respiratory viruses are in the nasal cavity and nasopharyngeal regions. Defining biomarkers of disease trajectory at the time of a positive diagnostic test would be an important tool to facilitate decisions such as initiation of antiviral treatment. We hypothesize that nasopharyngeal tRNA profiles could be used to predict Coronavirus Disease 19 (COVID-19) severity. We carried out multiplex small RNA sequencing (MSR-seq) on residual nasopharyngeal swabs to measure simultaneously full-length tRNA abundance, tRNA modifications, and tRNA fragmentation for the human tRNA response to SARS-CoV-2 infection. We identified distinct tRNA signatures associated with mild symptoms versus severe COVID-19 manifestations requiring hospitalization. These results highlight the utility of host tRNA properties as biomarkers for the clinical outcome of SARS-CoV-2.<\/jats:p>","DOI":"10.3389\/fcell.2022.999351","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T14:08:30Z","timestamp":1667311710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["tRNA abundance, modification and fragmentation in nasopharyngeal swabs as biomarkers for COVID-19 severity"],"prefix":"10.3389","volume":"10","author":[{"given":"Christopher D.","family":"Katanski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hala","family":"Alshammary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Gonzales-Reiche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia Mia","family":"Sordillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harm","family":"van Bakel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Mount Sinai PSP study group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Lolans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1126\/science.aaa1193","article-title":"Ribosome. The structure of the human mitochondrial ribosome","volume":"348","author":"Amunts","year":"2015","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4297","DOI":"10.1016\/j.febslet.2014.09.001","article-title":"tRNA fragments in human health and disease","volume":"588","author":"Anderson","year":"2014","journal-title":"FEBS Lett."},{"key":"B3","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/j.molcel.2007.09.021","article-title":"Trm9-catalyzed tRNA modifications link translation to the DNA damage response","volume":"28","author":"Begley","year":"2007","journal-title":"Mol. Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"D231","DOI":"10.1093\/nar\/gkab1083","article-title":"Modomics: A database of RNA modification pathways. 2021 update","volume":"50","author":"Boccaletto","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"D184","DOI":"10.1093\/nar\/gkv1309","article-title":"GtRNAdb 2.0: An expanded database of transfer RNA genes identified in complete and draft genomes","volume":"44","author":"Chan","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1261\/rna.056531.116","article-title":"tRNA base methylation identification and quantification via high-throughput sequencing","volume":"22","author":"Clark","year":"2016","journal-title":"RNA"},{"key":"B7","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1038\/nmeth.3508","article-title":"ARM-Seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments","volume":"12","author":"Cozen","year":"2015","journal-title":"Nat. Methods"},{"key":"B8","doi-asserted-by":"publisher","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1126\/science.abc1917","article-title":"Introductions and early spread of SARS-CoV-2 in the New York City area","volume":"369","author":"Gonzalez-Reiche","year":"2020","journal-title":"Science"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4287","DOI":"10.1016\/j.febslet.2014.09.038","article-title":"tRNA modifications regulate translation during cellular stress","volume":"588","author":"Gu","year":"2014","journal-title":"FEBS Lett."},{"key":"B11","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nrg.2016.169","article-title":"Detecting RNA modifications in the epitranscriptome: Predict and validate","volume":"18","author":"Helm","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/life6020016","article-title":"Multiple layers of stress-induced regulation in tRNA biology","volume":"6","author":"Huang","year":"2016","journal-title":"Life (Basel)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/mcse.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e4375","DOI":"10.1093\/cid\/ciaa1781","article-title":"Real-time investigation of a large nosocomial influenza A outbreak informed by genomic epidemiology","volume":"73","author":"Javaid","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5352","DOI":"10.1074\/jbc.REV118.002957","article-title":"Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication","volume":"294","author":"Jin","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.3390\/ijms17081278","article-title":"The ribonuclease A superfamily in humans: Canonical RNases as the buttress of innate immunity","volume":"17","author":"Koczera","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"W54","DOI":"10.1093\/nar\/gkw413","article-title":"tRNAscan-SE On-line: integrating search and context for analysis of transfer RNA genes","volume":"44","author":"Lowe","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.3389\/fimmu.2018.01012","article-title":"Immune modulation by human secreted RNases at the extracellular space","volume":"9","author":"Lu","year":"2018","journal-title":"Front. Immunol."},{"key":"B20","first-page":"51","article-title":"Data structures for statistical computing in python","volume":"445","author":"McKinney","year":"2010","journal-title":"Proc. 9th Python Sci. Conf."},{"key":"B21","volume-title":"mwaskom\/seaborn: v0.8.1","author":"Waskom","year":"2017"},{"key":"B22","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.tibs.2020.05.007","article-title":"Emerging roles of tRNAs in RNA virus infections","volume":"45","author":"Nunes","year":"2020","journal-title":"Trends biochem. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"607","DOI":"10.3390\/genes9120607","article-title":"tRNA-Derived small RNAs: Biogenesis, modification, function and potential impact on human disease development","volume":"9","author":"Oberbauer","year":"2018","journal-title":"Genes (Basel)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.omtn.2021.06.023","article-title":"Regulatory roles of tRNA-derived RNA fragments in human pathophysiology","volume":"26","author":"Pandey","year":"2021","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B25","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nrm.2017.77","article-title":"The emerging complexity of the tRNA world: Mammalian tRNAs beyond protein synthesis","volume":"19","author":"Schimmel","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1038\/s41467-022-30261-3","article-title":"A multiplex platform for small RNA sequencing elucidates multifaceted tRNA stress response and translational regulation","volume":"13","author":"Watkins","year":"2022","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.molcel.2021.12.007","article-title":"tRNA modification dynamics from individual organisms to metaepitranscriptomics of microbiomes","volume":"82","author":"Zhang","year":"2022","journal-title":"Mol. Cell"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.999351\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T14:08:35Z","timestamp":1667311715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.999351\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":28,"alternative-id":["10.3389\/fcell.2022.999351"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.999351","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]},"article-number":"999351"}}