Viruses that remain in the body for years, including Epstein-Barr virus, cytomegalovirus (CMV), and herpes virus, are very common. In many people, it causes no symptoms and appears harmless. But growing evidence suggests that when these dormant viruses become active again, they may play a role in autoimmune diseases and other long-term health conditions.
Now, researchers at Boston Children’s Hospital and collaborating institutions have found that COVID-19 can reactivate some dormant viruses in hospitalized patients. The results are back nature Study included 15 biomedical research institutions across the United States. The findings provide new insight into viruses that persist in the body and could ultimately help guide strategies to prevent or treat their reactivation.
Tracking hidden viruses during coronavirus (COVID-19).
Physician-scientist Ofer Levy, MD, director of the Precision Vaccines Program (PVP) at Boston Children’s Hospital, served as the principal investigator for the NIH-funded research site.
The study followed 1,154 patients at 20 biomedical research hospitals in the United States and was designed to identify biomarkers associated with coronavirus severity and patient outcomes. The researchers used genetic sequencing to look for signs that dormant viruses had become active again. Viral infections that have long since recovered from the active state can sometimes resurface when the body is under stress.
“This is the largest and most comprehensive biomarker study for COVID-19, in which we have followed more than a thousand patients, collected more than 200,000 samples, and generated more than a billion data points over the course of a year for this public resource,” says Joan Deray-Arce, Ph.D., who leads the PVP Data Management and Analysis Center and is the study’s clinical and data coordinating center leader.
11 viruses reactivate after hospitalization
Within the first 40 days after patients were hospitalized, researchers identified 11 reactivated viruses. The most commonly detected conditions included Epstein-Barr, herpes simplex 1, cytomegalovirus, and Circoviruses Viruses.
One result in particular stood out. Reactivation Circovirusesa poorly understood family of viruses that typically remain dormant in about 90 percent of the population, has shown a prominent association with long-term physical disability and long-lasting coronavirus.
“This association with long Covid is an interesting finding, as millions around the world suffer from this chronic condition,” Levy says. “Gaining new insight into the molecular and viral associations with long-term coronavirus could pave the way for better understanding and ultimately better diagnosis and treatments.”
Inflammation may lead to reactivation of the virus
Analysis of the blood sample also revealed an unexpected pattern involving Epstein-Barr virus and cytomegalovirus. Instead of these viruses appearing to reactivate due to suppression of the immune system, they appeared to reactivate in response to inflammation.
The researchers say the results point to a surprising mechanism and challenge the prevailing idea that chronic virus reactivation occurs mainly due to immunosuppression. The results show that dormant viruses can repeatedly reactivate in people who appear to have functioning immune systems during severe illness, especially when systemic inflammation is high.
“Although many no longer think COVID is a problem, as many as 50,000 Americans have died from COVID in the 2025-2026 respiratory season and some estimates suggest more than 10 million American adults have long-term COVID,” Levy says. “We need to help these patients recover with the best outcomes.” “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,” he adds.
Searching for better treatments
The researchers next plan to investigate how the immune system responds to these reactivated viruses throughout Covid-19. Their goal is to identify effective treatments and determine the best timing of possible interventions.
Other Boston Children’s researchers in the study include Jing Chen, Ph.D., Annemarie Hoch, Al Ozonoff, Ph.D., Kinga Smolin, Ph.D., and Hannu Steen, Ph.D.
