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Initial samples were obtained\u2009\u2264\u200914\u00a0days post-injury, and follow-up samples were obtained\u2009\u2265\u200921\u00a0days post-injury. Computerized balance and cognitive test performance were assessed at initial and follow-up time-points. Machine learning was used to define: (1) a model employing initial ncRNA levels to predict persistent post-concussion symptoms (PPCS)\u2009\u2265\u200921\u00a0days post-injury; and (2) a model employing follow-up ncRNA levels to identify symptom recovery. Performance of the models was compared against a validated clinical prediction rule, and balance\/cognitive test performance, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An algorithm using age and 16 ncRNAs predicted PPCS with greater accuracy than the validated clinical tool and demonstrated additive combined utility (area under the curve (AUC) 0.86; 95% CI 0.84\u20130.88). Initial balance and cognitive test performance did not differ between PPCS and non-PPCS groups (<jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05). Follow-up balance and cognitive test performance identified symptom recovery with similar accuracy to a model using 11 ncRNAs and age. A combined model (ncRNAs, balance, cognition) most accurately identified recovery (AUC 0.86; 95% CI 0.83\u20130.89).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ncRNA biomarkers show promise for tracking recovery from mTBI, and for predicting who will have prolonged symptoms. They could provide accurate expectations for recovery, stratify need for intervention, and guide safe return-to-activities.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00415-021-10566-x","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T11:03:07Z","timestamp":1621854187000},"page":"4349-4361","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Saliva RNA biomarkers predict concussion duration and detect symptom recovery: a comparison with balance and cognitive testing"],"prefix":"10.1007","volume":"268","author":[{"given":"Gregory","family":"Fedorchak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakanksha","family":"Rangnekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cayce","family":"Onks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea C.","family":"Loeffert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayson","family":"Loeffert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Olympia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"DeVita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Leddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad N.","family":"Haider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Uhlig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuck","family":"Monteith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Middleton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Zuckerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith Owen","family":"Yeates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Mannix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9579-6798","authenticated-orcid":false,"given":"Steven","family":"Hicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"10566_CR1","doi-asserted-by":"publisher","first-page":"e182853","DOI":"10.1001\/jamapediatrics.2018.2853","volume":"172","author":"A Lumba-Brown","year":"2018","unstructured":"Lumba-Brown A, Yeates KO, Sarmiento K, Breiding MJ, Haegerich TM, Gioia GA, Turner M, Benzel EC, Suskauer SJ, Giza CC (2018) Centers for Disease Control and Prevention guideline on the diagnosis and management of mild traumatic brain injury among children. 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SDH and FAM are scientific advisory board members for Quadrant Biosciences and are named as a co-inventors on intellectual property related to saliva RNA biomarkers in concussion that are patented by The Penn State College of Medicine and The SUNY Upstate Research Foundation and licensed to Quadrant Biosciences. SDV, GF, AR, and JR are paid employees of Quadrant Biosciences. RM has received funding from the NFL foundation. The other authors have no conflicts of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The authors hereby declare that the research documented in this manuscript has been carried out in accordance with the following ethical standards: all human studies have been approved by the appropriate ethics committee and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard"}}]}}