Viruses that remain in the body for years, including Epstein-Barr, cytomegalovirus (CMV), and herpes virus, are extremely common. In many people, they cause no symptoms and appear to be harmless. But growing evidence suggests that when these dormant viruses become active again, they may play a role in autoimmune diseases and other long-lasting health conditions.
Now, researchers at Boston Children’s Hospital and collaborating institutions have found that COVID 19 can reactivate certain dormant viruses in hospitalized patients. The findings come from a new Nature study involving 15 biomedical research institutions across the United States. The results provide new insight into viruses that persist in the body and could eventually help guide strategies for preventing or treating their reactivation.
Tracking Hidden Viruses During COVID-19
Physician scientist Ofer Levy, MD, PhD, director of the Precision Vaccines Program (PVP) at Boston Children’s, served as a site principal investigator for the National Institutes of Health (NIH) funded research.
The study followed 1,154 patients across 20 U.S. biomedical research hospitals and was designed to identify biomarkers associated with COVID severity and patient outcomes. Researchers used genomic sequencing to search for signs that dormant viruses had become active again. Viral infections that have long since cleared from an active state can sometimes reemerge when the body is under stress.
“This is the largest and most comprehensive biomarker study of COVID-19, in which we followed more than one thousand patients, collected more than 200,000 samples, and generated more than 1 billion data points over the course of a year for this public resource,” says Joann Diray Arce, PhD, who leads the PVP-Data Management and Analysis Core and is the lead of the study’s Clinical and Data Coordinating Center.
11 Viruses Reactivated After Hospital Admission
Within the first 40 days after patients were admitted to the hospital, the researchers identified 11 reactivated viruses. The most frequently detected included Epstein-Barr, herpes simplex 1, cytomegalovirus, and Anelloviridae viruses.
One finding stood out in particular. Reactivation of Anelloviridae, a poorly understood family of viruses that typically remains latent in about 90 percent of the population, showed a prominent association with long-term physical disability and long COVID.
“This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition,” says Levy. “Having new insight as to the molecular and viral associations with long COVID could point the way to better understanding and ultimately better diagnostics and treatments.”
Inflammation May Trigger Viral Reactivation
Blood sample analysis also revealed an unexpected pattern involving Epstein-Barr and cytomegalovirus. Rather than appearing to reactivate because the immune system had been suppressed, these viruses seemed to become active in response to inflammation.
Researchers say the finding points to a surprising mechanism and challenges the prevailing idea that chronic viral reactivation occurs mainly because of immunosuppression. The results show that dormant viruses can reactivate frequently in people who appear to have functioning immune systems during severe illness, particularly when systemic inflammation is elevated.
“Although many no longer think of COVID being a problem, up to 50,000 Americans died of COVID in 2025-2026 respiratory season and some estimates suggest over 10 million U.S. adults suffer from long COVID,” says Levy. “We need to help these patients recover with the best outcomes.” He adds, “Moreover, sooner or later, there may be another coronavirus pandemic, which means we need to learn all the lessons we can from COVID-19 to be better prepared.”
Searching for Better Treatments
The researchers next plan to investigate how the immune system responds to these reactivated viruses throughout the course of COVID 19. Their goal is to identify effective treatments and determine the best timing for possible interventions.
Other Boston Children’s researchers on the study include Jing Chen, PhD, Annmarie Hoch, Al Ozonoff, PhD, Kinga Smolen, PhD, and Hanno Steen, PhD.
