{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T08:58:54Z","timestamp":1781168334309,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,8]]},"group-title":"Immunology","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIDCR\/NIH","award":["R01DE027980"],"award-info":[{"award-number":["R01DE027980"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Periodontal disease and COVID-19 are linked by convergent immunoinflammatory pathways, yet the molecular basis of their interaction remains poorly defined. Here, we present a comprehensive salivary microRNA profile from individuals with prior SARS-CoV-2 infection, sampled approximately 3\u20136 months after diagnosis and meeting criteria for long COVID, providing new insight into the post-viral oral microenvironment. Salivary miRNA sequencing revealed widespread repression in patients with PD, consistent with persistent immune dysregulation. Relative to COVID-19-negative\/PD-negative controls, thirty-two miRNAs were differentially expressed in COVID-19-positive\/PD-positive individuals, all significantly downregulated. A similar signature was observed in a post-vaccination cohort for the selected dysregulated miRNAs. Integrative pathway analyses identified these miRNAs as regulators of core inflammatory circuits, including Ras, MAPK, and NF\u03baB signaling, converging on IL-1\u03b2- and TNF-centered networks relevant to both PD and COVID-19. Mechanistically, restoration of three downregulated miRNAs, miR- miR-30e-3p 106-3p-3p, and miR-652-3p attenuated NF\u03baB activation and cytokine release in TLR-stimulated human oral keratinocytes, while their functional suppression using inhibitors potentiates inflammation. These miRNAs were also predicted to target SARS-CoV-2 spike and nucleocapsid transcripts, an interaction validated by dual-luciferase reporter assays. Their overexpression further reduced spike and nucleocapsid expression in Beta- and Omicron-infected epithelial cells, as measured by flow cytometry and RT-qPCR confirming host miRNAs as potent endogenous SARS-CoV-2 restriction factor. Together, these findings identify salivary host miRNAs as mechanistic regulators of oral inflammatory tone and viral persistence, establishing a molecular link between periodontal inflammation and post-COVID oral pathology.<\/jats:p>","DOI":"10.64898\/2026.06.07.730729","type":"posted-content","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:35:24Z","timestamp":1780979724000},"source":"Crossref","is-referenced-by-count":0,"title":["Salivary microRNA Profiling of Long COVID Subjects Reveals Host-Encoded Regulators of Inflammation and Viral Persistence"],"prefix":"10.64898","author":[{"given":"Kristelle J.","family":"Capistrano","sequence":"first","affiliation":[{"name":"Department of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raza Ali","family":"Naqvi","sequence":"additional","affiliation":[{"name":"Department of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Elshourbagy","sequence":"additional","affiliation":[{"name":"Department of Periodontics, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA"},{"name":"Department of Periodontology, College of Dentistry, Cairo University, Cairo, 4240310, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Class","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M.","family":"Richner","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sodabeh","family":"Etminan","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, University of Illinois Health, Mile Square Health Center, Chicago, IL 60608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel L.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, College of Dentistry, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine D.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, College of Dentistry, University of Illinois 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