Dr. Akiko Iwasaki led analysis of the salivary samples at Yale University.
Medford, MA, May 23, 2026 —A collaborative study between the laboratory of Akiko Iwasaki at Yale University and the Cohen Center for Recovery from Complex Chronic Illness at the Icahn School of Medicine at Mount Sinai has identified a potential link between reactivation of the herpesvirus HHV-6 and Long COVID symptom severity. The work adds to growing evidence that chronic viral reactivation may contribute to the biological mechanisms underlying Long COVID.
The study examined whether reactivation of human herpesviruses could be associated with persistent symptoms following SARS-CoV-2 infection. Prior research has linked herpesvirus reactivation—particularly Epstein-Barr virus (EBV)—to more severe acute COVID-19 and increased risk of developing Long COVID. However, less is known about how active herpesvirus shedding relates to ongoing symptom burden over time.
Split violin plots showing viral copies of EBV and HHV-6 detected for each timepoint, averaged from 2 days.
To investigate this question, the research team enrolled 45 participants with Long COVID and 45 age- and sex-matched controls. Participants completed detailed symptom surveys and provided saliva samples at multiple timepoints across two consecutive days. The team measured salivary cortisol, testosterone, and estradiol levels while simultaneously testing saliva for DNA from multiple herpesviruses—including EBV, HSV-1/2, HCMV, and HHV-6 A/B—alongside SARS-CoV-2 RNA.
The researchers found that detection of EBV and HHV-6 DNA was highest early in the morning. While overall herpesvirus shedding and hormone levels did not significantly differ between Long COVID participants and controls, one signal stood out: higher levels of salivary HHV-6 DNA were associated with greater Long COVID symptom severity, including stronger associations with anxiety, depression, and overall functional impairment.
The findings suggest that HHV-6 reactivation may contribute to chronic disease processes in at least a subset of Long COVID patients. The researchers note that while salivary EBV shedding was not associated with Long COVID in this cohort, EBV could still play a role earlier in disease progression or within tissues not sampled in the study.
The work also raises important translational questions. If future studies replicate the findings, HHV-6 could become a target for biomarker-guided clinical trials and therapeutic intervention strategies. Researchers suggest that salivary virome profiling may eventually help identify biologically distinct patient subsets who could benefit from tailored antiviral or immunomodulatory therapies.
About PolyBio Research Foundation
PolyBio Research Foundation is a 501(c)(3) organization advancing research on how viral, bacterial, and parasitic infections drive chronic disease and aging. We build collaborative projects that identify, diagnose, and treat root causes of infection-associated chronic illness.