{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T01:29:03Z","timestamp":1778722143846,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas (CONACYT), Mexico","award":["312992"],"award-info":[{"award-number":["312992"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: The metabolome of COVID-19 patients has been studied sparsely, with most research focusing on a limited number of plasma metabolites or small cohorts. This is the first study to test saliva metabolites in COVID-19 patients in a comprehensive way, revealing patterns significantly linked to disease and severity, highlighting saliva\u2019s potential as a non-invasive tool for pathogenesis or diagnostic studies. Methods: We included 30 asymptomatic subjects with no prior COVID-19 infection or vaccination, 102 patients with mild SARS-CoV-2 infection, and 61 hospitalized patients with confirmed SARS-CoV-2 status. Saliva samples were analyzed using hydrophilic interaction liquid chromatography\u2013mass spectrometry (HILIC-MS\/MS) in positive and negative ionization modes. Results: Significant differences in metabolites were identified in COVID-19 patients, with distinct patterns associated with disease severity. Dipeptides such as Val-Glu and Met-Gln were highly elevated in moderate cases, suggesting specific protease activity related to SARS-CoV-2. Acetylated amino acids like N-acetylserine and N-acetylhistidine increased in severe cases. Bacterial metabolites, including muramic acid and indole-3-carboxaldehyde, were higher in mild\u2013moderate cases, indicating that oral microbiota differs according to disease severity. In severe cases, polyamines and organ-damage-related metabolites, such as N-acetylspermine and 3-methylcytidine, were significantly increased. Interestingly, most metabolites that were reduced in moderate cases were elevated in severe cases. Conclusions: Saliva metabolomics offers insightful information that is potentially useful in studying COVID-19 severity and for diagnosis.<\/jats:p>","DOI":"10.3390\/metabo15030192","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T08:59:52Z","timestamp":1741683592000},"page":"192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0052-4376","authenticated-orcid":false,"given":"Violeta","family":"Larios-Serrato","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-3526","authenticated-orcid":false,"given":"Natalia","family":"V\u00e1zquez-Manjarrez","sequence":"additional","affiliation":[{"name":"Unidad de Metabol\u00f3mica, Departamento Fisiologia de la Nutricion, Instituto de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-541X","authenticated-orcid":false,"given":"Osbaldo","family":"Resendis-Antonio","sequence":"additional","affiliation":[{"name":"Human Systems Biology Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Centro de Ciencias de la Complejidad & Coordinaci\u00f3n de la Investigaci\u00f3n Cient\u00edfica-Red de Apoyo a la Investigaci\u00f3n, Universidad Nacional Autonoma de Mexico, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-0581","authenticated-orcid":false,"given":"Nora","family":"Rios-Sarabia","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Infecciosas, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City 06920, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Meza","sequence":"additional","affiliation":[{"name":"Departamento Acad\u00e9mico de Ciencia Animal y Conservaci\u00f3n del H\u00e1bitat, Departamento Acad\u00e9mico de Ingenier\u00edas en Pesquer\u00edas, Universidad Aut\u00f3noma de Baja California Sur, La Paz 023080, Mexico"},{"name":"Centro de Investigaciones Biol\u00f3gicas del Noroeste SC, La Paz 23205, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-8928","authenticated-orcid":false,"given":"Oliver","family":"Fiehn","sequence":"additional","affiliation":[{"name":"NIH West Coast Metabolomics Center, UC Davis Genome Center, Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3945-4221","authenticated-orcid":false,"given":"Javier","family":"Torres","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Enfermedades Infecciosas, UMAE Pediatr\u00eda, Centro M\u00e9dico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City 06920, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"ref_1","unstructured":"(2025, February 20). 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