Severe COVID-19 can reactivate dormant viruses hidden in the human body, such as the Epstein-Barr virus and Anelloviridae, according to a large observational study published in Nature. Researchers analyzed data from more than 1,100 hospitalized, unvaccinated patients across 20 U.S. hospitals to understand how viral reawakening impacts clinical outcomes and long COVID.
Reactivating the Body’s Hidden Ecosystem
Most people carry between eight and 12 generally harmless viruses at any given time. These persistent pathogens typically remain dormant, kept in check by the immune system until physiological stress, severe illness, or sleep deprivation allows them to surface. However, a major new observational analysis demonstrates that severe COVID-19 infections can reactivate these dormant viruses, disrupting what researchers describe as the body’s internal viral ecosystem.
The study utilized longitudinal data from 1,154 hospitalized COVID-19 patients participating in the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study. By tracking unvaccinated patients across 20 U.S. hospitals from May 2020 to March 2021, the research team generated more than 1 billion data points from 200,000 nasal swabs, blood cells, and endotracheal aspirates. Unlike previous studies that relied on antibody responses, this research measured the RNA of actively replicating viruses to capture precise temporal dynamics.
“This finding suggests that COVID-19 may not always act as a single viral infection and may disrupt the body’s internal ecosystem of dormant viruses.”
Nearly half of the hospitalized patients exhibited at least one dormant virus springing back to life during their illness. The reawakened pathogens frequently included members of the herpes family, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex 1, alongside poorly understood Anelloviridae viruses.
Challenging Assumptions About Immune Suppression
Medical understanding has long held that chronic viruses reawaken primarily when a patient’s immune system is severely suppressed. The new findings challenge that prevailing view. Researchers observed that viral reactivation occurred frequently in individuals who were healthy prior to contracting SARS-CoV-2.
Patients whose dormant infections resurfaced experienced worse clinical trajectories, including longer hospital stays, severe complications, and an increased likelihood of mortality.
When limiting analysis to severely ill patients, those with CMV in the respiratory tract or EBV in the nasal cavity faced a higher probability of dying within one year.
Connection to Long COVID and Physical Disability
While the study does not definitively prove that reactivated dormant viruses cause long COVID, it uncovers a compelling viral signal that may help explain the debilitating chronic condition. Researchers discovered a strong association of Anelloviridae with long COVID and long-term physical disability.
Anelloviridae, a poorly understood virus family that remains dormant in roughly 90% of people, showed persistent activity well into convalescence.
Long COVID remains a massive global challenge.
Pathways to Future Prognostication and Treatment
The discovery of multi-omic signatures of viral reactivation opens new avenues for clinical management. Because diagnostic tests already exist for several of the chronic viruses studied, medical professionals may soon be able to target these reactivated pathogens directly.
Because the patients in the IMPACC study were hospitalized, unvaccinated, and infected early in the pandemic, it remains uncertain whether identical patterns hold with current viral variants and widespread population immunity. Even so, the findings provide a framework for future strategies to prognosticate and treat both acute illness and its lingering aftermath.
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