Severe COVID-19 Reactivates Dormant Viruses, Major New Study Finds

Severe COVID-19 can trigger the reactivation of multiple viruses already living dormant in the body, a major new study published in the journal Nature has found — offering some of the most detailed evidence yet of how SARS-CoV-2 disrupts the broader viral ecosystem and potentially setting the stage for long-term health consequences.

Scale and Scope of the Research

Researchers from Boston Children’s Hospital and collaborators from more than 20 biomedical research institutions across the United States and Canada analyzed more than 200,000 biological samples collected over one year from 1,154 patients hospitalized with COVID-19. The study, known as the IMPACC cohort, is one of the largest and most comprehensive investigations of viral dynamics during severe COVID-19 to date.

The severe COVID-19 dormant virus reactivation long COVID study team detected RNA from 11 different latent viruses that had reactivated within the first 40 days of hospitalization. The most commonly reactivated were herpes simplex virus 1 and the Anelloviridae family of viruses — which establish lifelong infections in most people but are generally considered harmless — as well as Epstein-Barr virus, cytomegalovirus, and enteroviruses.

What Reactivation Means

Many viruses remain silently dormant in the body long after the original infection clears. In healthy individuals, the immune system keeps them suppressed. But during periods of severe illness or stress, those viruses can re-emerge — a process called reactivation. The study found that COVID-19 appeared to provide precisely those conditions.

Epstein-Barr virus tended to reactivate early in the course of illness, while cytomegalovirus and herpes simplex virus 1 were more commonly detected later and particularly in respiratory samples. Epstein-Barr virus and cytomegalovirus reactivation correlated with systemic inflammation rather than immune suppression — a finding that offers a new window into the biological mechanisms driving severe COVID-19.

“It was not previously known to this degree of detail and scale how viral reactivation might associate with COVID severity and outcome,” said lead author Ofer Levy of Boston Children’s Hospital, in a statement to ABC News.

What the Study Does Not Prove

Experts were careful to note significant limits on the findings. The study demonstrated an association between viral reactivation and severe COVID-19, but did not prove that reactivated viruses cause long COVID or any specific long-term disability.

“The authors carefully do NOT attribute any disease — including long COVID — to the reactivated viruses,” said infectious disease expert Dr. William Schaffner of Vanderbilt University Medical Center. “It is not clear whether they play any role in disease production; this may be an entirely coincidental event.”

The research also has structural limitations: it studied unvaccinated patients hospitalized with ancestral SARS-CoV-2 strains before mid-2021, meaning the findings may not apply directly to vaccinated individuals, milder infections, or patients exposed to newer COVID variants.

Researchers also cautioned that the study did not find a clear link between viral reactivation during the initial infection and the different clusters of long COVID symptoms they studied — meaning the picture of whether reactivation contributes to persistent illness remains incomplete.

Why It Matters Despite Uncertainty

The findings are significant even in the absence of definitive causal proof, because they open new avenues for understanding COVID-19 complications and could inform the development of future diagnostic tools and treatments. The study suggested that monitoring hospitalized COVID patients for Herpesviridae and Anelloviridae reactivation using already-validated PCR infrastructure could be a practical next step.

Levy noted that COVID-19 remains a meaningful public health concern despite fading from the headlines. “Although the pandemic is over, SARS-CoV-2 continues to cause infections with both acute and long-term consequences,” he wrote. An estimated 50,000 Americans died of COVID during the 2025-2026 respiratory season, and up to 10 million may have experienced long COVID in the past year, according to his estimates. “Immunization of vulnerable populations such as older adults remains very important to avoid severe outcomes.”