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We studied saliva from 63 hospitalized COVID\u201019 patients and from 30 healthy controls by integrating large\u2010scale proteomics, peptidomics and targeted metabolomics to assess the biochemical alterations following the infection and to obtain a set of putative biomarkers useful for noninvasive diagnosis. We used an untargeted approach by using liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) for proteomics and peptidomics analysis and targeted LC\u2013multiple reaction monitoring\/MS for the analysis of amino acids. The levels of 77 proteins were significantly different in COVID\u201019 patients. Among these, seven proteins were found only in saliva from patients with COVID\u201019, four were up\u2010regulated and three were down\u2010regulated at least five\u2010folds in saliva from COVID\u201019 patients in comparison to controls. The analysis of proteins revealed a complex balance between pro\u2010inflammatory and anti\u2010inflammatory proteins and a reduced amount of several proteins with immune activity that possibly favours the spreading of the virus. Such reduction could be related to the enhanced activity of endopeptidases induced by the infection that in turn caused an altered balance of free peptides. In fact, on a total of 28 peptides, 22 (80%) were differently expressed in severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) and control subjects. The multivariate analysis of such peptides permits to obtain a diagnostic algorithm that discriminate the two populations with a high diagnostic efficiency. Among amino acids, only threonine resulted significantly different between COVID\u201019 patients and controls, while alanine levels were significantly different between COVID\u201019 patients with different severity. In conclusion, the present study defined a set of molecules to be detected with a quick and easy method based on mass spectrometry tandem useful to reveal biochemical alterations involved in the pathogenesis of such a complex disease. Data are available via ProteomeXchange with identifier PXD045612.<\/jats:p>","DOI":"10.1002\/jms.5082","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T03:23:08Z","timestamp":1725420188000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular fingerprint by omics\u2010based approaches in saliva from patients affected by SARS\u2010CoV\u20102 infection"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9169-3452","authenticated-orcid":false,"given":"Gabriella","family":"Pinto","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Chimiche University of Naples Federico II  Naples Italy"},{"name":"Istituto Nazionale Biostrutture e Biosistemi\u2010Consorzio Interuniversitario  Rome 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