{
  "abstract": "Background: Reactivation of human herpesviruses (HHVs), particularly EBV, is associated with more severe acute SARS-CoV-2 infection and the development of Long COVID (LC). Reactivation of HHVs has been previously implicated in hormonal dysregulation, which has also been observed in LC, suggesting a potential link. This study aims to examine the relationship between LC symptoms and salivary HHV DNA, cortisol, testosterone, and oestradiol levels.\n\nMethods: Our cross-sectional, case–control study enrolled 45 participants with LC, and 45 age-sex-matched controls. Surveys and validated health questionnaires were used to collect demographics, medical history, and symptom profiles. Saliva was self-collected at waking, 15, 30, and 45 min, and 8 and 16 h after waking, across two consecutive days. Salivary cortisol, testosterone and oestradiol were measured, and extracted nucleic acid was tested for EBV, HSV 1/2, HCMV and HHV-6 A/B using multiplex qPCR, and for SARS-CoV-2 and RNaseP using RT-qPCR.\n\nFindings: Detection of salivary EBV and HHV-6 DNA copies was highest early in the morning. There were no significant differences in salivary cortisol, testosterone, or oestradiol, or in EBV or HHV-6 DNA between the LC and control groups. However, salivary HHV-6 DNA levels were positively associated with a greater aggregated LC propensity score (r = 0.24, 95% CI = 0.02–0.44, p = 0.015, adj. p = 0.030), as well as anxiety (β = 0.69, 95% CI = 0.02–1.36, p = 0.045) and depression (β = 0.24, 95% CI = 0.05–0.42, p = 0.013) scores.\n\nInterpretation: The observed correlation between salivary HHV-6 DNA and symptom severity suggests HHV-6 may contribute to post-acute disease, though mechanisms remain unclear. While we did not identify a relationship between salivary EBV DNA and LC, EBV may still play a role at earlier time points in the disease course, or in compartments not sampled in this study. These findings highlight the potential importance of HHV-6 in LC pathophysiology and underscore the need for longitudinal, multi-compartment studies of herpesvirus reactivation in LC.\n\nFunding: This work was supported in part by the Else Kröner Fresenius Prize for Medical Research 2023 (to AI), the Howard Hughes Medical Institute Collaborative COVID-19 Initiative (to AI), and the 10.13039/100000011Howard Hughes Medical Institute (to AI), the Polybio Research Foundation (to AI and DP) and the 10.13039/100016230Steven and Alexandra Cohen Foundation (to DP). National Institutes for Health (NIH) funding sources supported AT, SB and CM.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "Claire S. Laxton",
      "orcid": "0000-0002-0642-2015"
    },
    {
      "name": "Alexandra Tabachnikova",
      "orcid": "0000-0003-4695-2480"
    },
    {
      "name": "Lily Cooke",
      "orcid": "0009-0003-9529-0249"
    },
    {
      "name": "Kexin Wang"
    },
    {
      "name": "Simone Blaser",
      "orcid": "0009-0007-2701-9835"
    },
    {
      "name": "Julio Silva"
    },
    {
      "name": "Jamie Wood"
    },
    {
      "name": "Henna S. Nam"
    },
    {
      "name": "Zhenni Lu"
    },
    {
      "name": "Christine Miller",
      "orcid": "0000-0003-0486-5047"
    },
    {
      "name": "Gisele Rodrigues"
    },
    {
      "name": "Victoria Fisher"
    },
    {
      "name": "Christian Guirgis"
    },
    {
      "name": "William B. Hooper",
      "orcid": "0000-0002-1054-0866"
    },
    {
      "name": "Alexandra Lee"
    },
    {
      "name": "Mackenzie Doerstling"
    },
    {
      "name": "Bornali Bhattacharjee"
    },
    {
      "name": "Leying Guan"
    },
    {
      "name": "David Putrino"
    },
    {
      "name": "Akiko Iwasaki",
      "orcid": "0000-0002-7824-9856"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6m3m602nkwxe9.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ebiom.2026.106525",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733318/",
  "id": "6m3m602nkwxe9",
  "issns": [
    "2352-3964"
  ],
  "landing_url": "https://linkinghub.elsevier.com/retrieve/pii/S2352396426004093",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Articles"
    ],
    [
      "openalex",
      "2728|Long-Term Effects of COVID-19"
    ]
  ],
  "openalex": "W7223916169",
  "pdf_url": null,
  "pmcid": "PMC13733318",
  "pmid": "42945894",
  "published": "2026-10-27",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/6m3m602nkwxe9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:49Z",
      "native_id": "10.1016/j.ebiom.2026.106525",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2352396426004093"
    },
    {
      "first_seen": "2026-11-08T12:23:08Z",
      "native_id": "PMC13733318",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.ebiom.2026.106525"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Long-Term Effects of COVID-19",
      "subfield": "neurology"
    }
  ],
  "title": "Associations between salivary HHV-6 and long COVID severity in a cross-sectional, case–control analysis",
  "title_text": "Associations between salivary HHV-6 and long COVID severity in a cross-sectional, case–control analysis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:08Z",
  "url": "https://research.draconitic.com/paper/6m3m602nkwxe9",
  "venue": "eBioMedicine",
  "versions": []
}