{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T08:01:49Z","timestamp":1768032109565,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,5]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":20,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Epstein\u2013Barr virus (EBV) establishes latency in most adults and can be reactivated under conditions of co-infection and immune dysregulation. COVID-19 has been associated with EBV reactivation, primarily in hospitalized cohorts, but EBV shedding in the oral cavity and the extent to which these dynamics trigger a systemic anti-EBV antibody response during acute COVID-19 remain poorly understood.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a nested cohort study of 69 community-based participants including 56 SARS-CoV-2\u2013positive individuals and 13 uninfected household contacts, enrolled as part of a prospective cohort within 5 days of COVID-19 symptom onset. Participants self-collected saliva and nasal samples daily through day 14, then every 3 days until day 21, and once more at day 28. Blood samples were collected on day 28. SARS-CoV-2 RNA in the saliva and nares and EBV DNA in the saliva were quantified by RT-qPCR and qPCR, respectively. EBV antibody responses against viral capsid antigen IgM and IgG, early (D) antigen IgG, and nuclear antigen IgG were quantified in serum by ELISA.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    SARS-CoV-2\u2013positive participants tended to be more likely to experience consecutive days of EBV shedding in saliva (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.10) and contributed a higher mean number of EBV DNA\u2013positive specimens compared with uninfected controls (5 vs. 1 per participant in EBV+ participants;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.018). Among SARS-CoV-2\u2013positive participants with EBV reactivation, a positive correlation was observed between maximum EBV DNA in saliva and SARS-CoV-2 RNA levels in saliva (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.49,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.047) but not with SARS-CoV-2 RNA levels in nasal samples (\n                    <jats:italic>r<\/jats:italic>\n                    = -0.12,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.67). EBV reactivation in saliva was not associated with induction of serological responses to systemic EBV reactivation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This cohort study provides evidence that SARS-CoV-2 infection is associated with prolonged salivary EBV shedding, that concurrent high levels of EBV and SARS-CoV-2 in saliva are correlated, but these salivary EBV shedding dynamics do not drive systemic EBV antibody responses. Further research with larger cohorts and mechanistic assays would be helpful to elucidate the biological pathway triggering systemic EBV antibody responses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.31.25343091","type":"posted-content","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:30:14Z","timestamp":1767652214000},"source":"Crossref","is-referenced-by-count":0,"title":["Epstein Barr viral shedding dynamics in saliva during acute SARS-CoV-2 infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9556-3719","authenticated-orcid":false,"given":"Miguel A.","family":"Garcia-Knight","sequence":"first","affiliation":[{"name":"Departamento de Inmunolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico"},{"name":"Wellcome Sanger Institute, Hinxton, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4491-2584","authenticated-orcid":false,"given":"Jessica Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of California San Francisco, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amethyst","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of California San Francisco, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-8796","authenticated-orcid":false,"given":"Michel","family":"Tassetto","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of California San Francisco, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-6257","authenticated-orcid":false,"given":"Isidro X","family":"Perez-A\u00f1orve","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Naturales, Unidad Cuajimalpa, Universidad Autonoma Metropolitana, 05348 Mexico City, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8642-1468","authenticated-orcid":false,"given":"Sarah A.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khamal","family":"Anglin","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4779-5037","authenticated-orcid":false,"given":"Badri","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-747X","authenticated-orcid":false,"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6684-0622","authenticated-orcid":false,"given":"Timothy","family":"Henrich","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9773-3256","authenticated-orcid":false,"given":"Jeffrey N.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-6230","authenticated-orcid":false,"given":"Michael J.","family":"Peluso","sequence":"additional","affiliation":[{"name":"Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-9349","authenticated-orcid":false,"given":"Raul","family":"Andino","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of California San Francisco, San Francisco, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7616-0321","authenticated-orcid":false,"given":"J. Daniel","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA"},{"name":"San Francisco VA Medical Center, Department of Medicine, University of California, San Francisco, San Francisco, California, USA"},{"name":"Institute for Global Health Sciences, University of California, San Francisco, San Francisco, California, USA"},{"name":"F.I. Proctor Foundation, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026010920402757000_2025.12.31.25343091v2.1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens1020156"},{"key":"2026010920402757000_2025.12.31.25343091v2.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000496"},{"key":"2026010920402757000_2025.12.31.25343091v2.3","doi-asserted-by":"crossref","unstructured":"Indari O , et al. Awakening the sleeping giant: Epstein\u2013Barr virus reactivation by biological agents. Pathog Dis. 2024;82:ftae002.","DOI":"10.1093\/femspd\/ftae002"},{"key":"2026010920402757000_2025.12.31.25343091v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.01.014"},{"issue":"3","key":"2026010920402757000_2025.12.31.25343091v2.5","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.idnow.2021.01.005","article-title":"High incidence of Epstein\u2013Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19","volume":"51","year":"2021","journal-title":"Infectious Diseases Now"},{"issue":"6","key":"2026010920402757000_2025.12.31.25343091v2.6","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3390\/pathogens10060763","article-title":"Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation","volume":"10","year":"2021","journal-title":"Pathogens"},{"key":"2026010920402757000_2025.12.31.25343091v2.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06211-2"},{"key":"2026010920402757000_2025.12.31.25343091v2.8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI163669"},{"key":"2026010920402757000_2025.12.31.25343091v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06651-y"},{"issue":"Suppl 2","key":"2026010920402757000_2025.12.31.25343091v2.10","first-page":"S193","article-title":"Magnitude and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Household Transmission: A Longitudinal Cohort Study","volume":"75","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2026010920402757000_2025.12.31.25343091v2.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010802"},{"key":"2026010920402757000_2025.12.31.25343091v2.12","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20581"},{"key":"2026010920402757000_2025.12.31.25343091v2.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2206449"},{"key":"2026010920402757000_2025.12.31.25343091v2.14","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00164-09"},{"key":"2026010920402757000_2025.12.31.25343091v2.15","doi-asserted-by":"crossref","unstructured":"Skuhala T , et al. Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study. Acta Stomatol Croat;58(1):76\u201384.","DOI":"10.15644\/asc58\/1\/7"},{"key":"2026010920402757000_2025.12.31.25343091v2.16","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.02333-20"},{"key":"2026010920402757000_2025.12.31.25343091v2.17","first-page":"77","article-title":"Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences in Participants Treated With Nirmatrelvir Plus Ritonavir Versus Untreated Controls","volume":"2023","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2026010920402757000_2025.12.31.25343091v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.054"},{"key":"2026010920402757000_2025.12.31.25343091v2.19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2006.00865.x"},{"key":"2026010920402757000_2025.12.31.25343091v2.20","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.11811"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2025.12.31.25343091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T04:40:32Z","timestamp":1768020032000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2025.12.31.25343091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":20,"URL":"https:\/\/doi.org\/10.64898\/2025.12.31.25343091","relation":{},"subject":[],"published":{"date-parts":[[2026,1,5]]},"subtype":"preprint"}}