COVID-19 May Reactivate Dormant Viruses, Study Finds

A large study of people hospitalized with COVID-19 found that the infection was frequently accompanied by reactivation of viruses that can remain dormant in the body for years. Conducted across 15 biomedical research institutions in the United States, the findings may help us better understand how severe infections disrupt the immune system and whether reactivated viruses contribute to complications of acute COVID-19 or long COVID.

Researchers analyzed samples from 1,154 people hospitalized with COVID-19 at 20 U.S. hospitals, collecting more than 200,000 samples and generating more than 1 billion data points over the course of a year. Using RNA sequencing and other molecular analyses, they looked for evidence that persistent viruses had become active again and tracked these changes over time.

Nearly half of participants had evidence of at least one reactivated virus during the first 40 days after hospitalization.

Several viruses showed distinct patterns of reactivation. Epstein-Barr virus (EBV) tended to become active early in the course of illness, while cytomegalovirus (CMV) and herpes simplex virus 1 (HSV-1) were more likely to appear later. Reactivation of viruses from the Herpesviridae and Anelloviridae families was associated with more severe COVID-19, greater systemic inflammation, and several clinical complications.

Importantly, these reactivations were not limited to people taking immunosuppressive medications, suggesting that severe illness and inflammation may be enough to disrupt the normal control of persistent viruses.

The researchers also examined whether viral activity was associated with long COVID. They did not find that EBV reactivation during acute COVID-19 predicted who later developed long COVID. However, during recovery, members of the Anelloviridae family were detected more often in people who reported persistent physical limitations, even after the researchers accounted for factors including age, COVID-19 severity, and use of immunosuppressive medications. Anelloviruses are extremely common and remain poorly understood, so the finding does not establish that they cause long COVID.

Persistent viral infections have also been studied in connection with autoimmune disease, making the interaction between SARS-CoV-2, dormant viruses, and the immune system particularly relevant to autoimmune research. The authors emphasize that their findings show associations rather than cause and effect. Future studies will be needed to determine whether viral reactivation contributes directly to ongoing inflammation or disease, or instead serves as a marker of broader immune disruption during and after severe infection.

Citation

Maguire, C., Chen, J., Rouphael, N. et al. Virus reactivation in acute and long COVID-19. Nature (2026). https://doi.org/10.1038/s41586-026-10740-z