Severe COVID-19 can reactivate up to 11 dormant viruses within the human body, including Epstein-Barr and the Anelloviridae family, according to a large observational study published in Nature. Researchers found that viral awakenings are driven by systemic inflammation rather than simple immune suppression, pointing to new pathways for understanding long-term complications.
Dormant Viral Activity Tracked Across 20 US Hospitals
Most people carry between eight and 12 harmless viruses that remain in a latent state throughout life, kept in check by a functioning immune system. However, a major observational analysis utilizing data from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study reveals that severe SARS-CoV-2 infections can disrupt this balance. The research evaluated biological samples from 1,154 unvaccinated patients hospitalised across 20 American institutions between May 2020 and March 2021.
By examining more than 200,000 biological specimens—including nasal swabs, blood cells, and endotracheal aspirates—scientists tracked the active replication of viral RNA rather than relying on historical antibody responses. The findings demonstrate that critical illness creates biological conditions allowing chronic viruses to break dormancy, a process with implications that can outlast the initial infection by months.
Inflammation Drives Viral Awakening Over Immune Collapse
The consensus among researchers prior to this analysis held that chronic viral reactivation stems primarily from systemic immunosuppression. Yet the study challenges that presumption. According to the data, specific herpesviruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV) appeared to reawaken directly in response to heightened systemic inflammation.
This mechanism reframes post-viral syndromes as inflammatory disorders as much as immunological ones. Dr. Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital, noted the unprecedented scale of the investigation.
“It was not previously known to this degree of detail and scale how viral reactivation (i.e. the ‘waking up’ and replication of non-SARS-CoV-2 viruses that live in our body — such as herpes viruses) might associate with COVID severity and outcome.”
Dr. Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital, via Livemint
Different viruses displayed distinct temporal patterns following hospital admission. EBV tended to reactivate early in the clinical course, with detectable RNA appearing in roughly 24 per cent of patients near admission before gradually declining. Conversely, CMV and herpes simplex virus 1 (HSV-1) frequently surfaced later, particularly within respiratory samples from severely ill patients.
Anelloviridae Reactivation Tied to Physical Disability
Among the 11 reactivated viruses identified within the first 40 days of hospital admission, members of the Anelloviridae family drew particular attention from researchers. While this poorly understood group of viruses remains dormant in roughly 90 per cent of the healthy population without causing definitive disease, its reactivation during acute COVID-19 showed a strong statistical correlation with prolonged illness and long-term physical disability.
Separately, severe manifestations involving specific pathogens carried distinct clinical risks. Patients exhibiting CMV in their nasal cavities showed a higher likelihood of developing a collapsed lung, or pneumothorax, while CMV detected in blood cells correlated with conditions including pulmonary vascular disease, kidney complications, stroke, and shock.
Therapeutic Implications and Expert Caution
“The authors carefully do NOT attribute any disease (including long COVID) to [the reactivated viruses]. It is not clear whether they play any role in disease production; this may be an entirely coincidental event.”
Dr. William Schaffner, professor of preventive medicine at Vanderbilt University Medical Center, via Livemint
For now, the data provides a detailed map of how acute viral infection perturbs the human body’s viral archive, offering a foundation for future prognostic tools and anti-inflammatory treatment strategies.
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