Researchers analyzing hospital records from over 1,100 patients find that severe COVID-19 can reactivate dormant viruses, including Epstein-Barr and anelloviruses, in nearly half of hospitalized individuals. Published in Nature, the study reveals that systemic inflammation appeared to reanimate Epstein-Barr and cytomegalovirus, offering new clues into long COVID.
A major new study reveals that severe COVID-19 can awaken dormant viruses that have remained hidden in the human body for years. Conducted by researchers at Dell Medical School at The University of Texas at Austin and a national consortium, the research examined samples from hospitalized patients to understand how a coronavirus infection disrupts the body’s internal viral ecosystem.
Most humans carry a collection of harmless, latent viruses that stay under control thanks to immune surveillance. However, the new findings show that severe illness can flip the switch on these dormant pathogens. Nearly half of the hospitalized participants experienced a reactivation of at least one chronic virus during their acute illness.
How COVID-19 Reactivates Epstein-Barr, Cytomegalovirus, and Anelloviruses
The study, published in Nature, tracked 1,154 unvaccinated individuals hospitalized with COVID-19 across 20 U.S. hospitals between May 2020 and March 2021. Researchers utilized longitudinal data from the National Institutes of Health-funded Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, analyzing more than 200,000 nasal swabs, blood cells, and respiratory secretions to generate over 1 billion data points.
Instead of relying solely on antibody responses, the research team measured the RNA of actively replicating viruses. They discovered that 11 different dormant viruses reawakened within the first 40 days after hospital admission. The most frequently detected pathogens included herpes simplex 1 and Anelloviridae viruses, and to a lesser extent, Epstein-Barr (EBV), CMV, and enteroviruses.
Different viruses emerged at distinct stages of the illness. Epstein-Barr virus and anelloviruses were most commonly detected early on, whereas cytomegalovirus and herpes simplex virus 1 tended to be detected later, peaking roughly three weeks after hospital admission.
Challenging Assumptions About Immune Suppression and Severe Illness
Medical science has traditionally attributed the reactivation of chronic viruses to a suppressed or weakened immune system. However, the latest findings challenge that long-standing belief.
Furthermore, this viral reawakening was not limited to immunocompromised individuals. Many patients who experienced flare-ups had been healthy before contracting COVID-19.
The study linked viral detection to worse clinical outcomes. Patients with reactivated viruses experienced more severe illness, longer hospital stays, and a higher likelihood of complications.
Anelloviruses and the Ongoing Mystery of Long COVID
Researchers examined whether viral reactivation contributes to the condition. While the study did not establish definitive causation, it uncovered a striking correlation.
Patients experiencing persistent fatigue and physical impairment months after hospitalization were more likely to show evidence of anellovirus activity at least three months after hospitalisation. About 90 percent of people carry anelloviruses without symptoms, but prolonged activity from this family of viruses has previously been linked to chronic conditions, such as chronic fatigue syndrome and multiple sclerosis.
Esther Melamed, assistant professor of neurology at Dell Medical School and the study’s principal investigator, noted that the findings could pave the way for new therapeutic strategies.
While investigators continue to study whether treating these underlying reactivated pathogens can alleviate chronic symptoms, the research underscores how a severe respiratory infection can profoundly destabilize the body’s internal microbial ecosystem.
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