Severe COVID-19 infection can rouse a host of dormant viruses that most people carry silently for life, according to a large U.S. study that tracked more than a thousand hospitalized patients for signs of viral reactivation. The research, published in Nature and led by investigators at Boston Children's Hospital, offers one of the most detailed pictures yet of how the body's dormant viruses respond to acute infection.
Researchers followed 1,154 hospitalized COVID-19 patients across 20 U.S. medical centers, collecting more than 200,000 biological samples and generating over a billion data points across roughly a year of monitoring. Within the first 40 days of hospital admission, the team detected reactivation of 11 different viruses, most commonly Epstein-Barr virus, herpes simplex virus-1, cytomegalovirus, and members of the little-studied Anellovirus family, which lies dormant in an estimated 90 percent of the general population.
An inflammation link, not just a weak immune system
The study challenges a long-standing assumption that dormant viruses reactivate mainly because a patient's immune system has been suppressed. Blood analysis showed Epstein-Barr and cytomegalovirus activity rising in step with markers of inflammation, suggesting the body's own inflammatory response, not immune weakness, can flip these viruses back on.
The most striking clinical link involved Anelloviruses: their reactivation was associated with long-term physical disability and with long COVID, the cluster of lingering symptoms that researchers estimate affects more than 10 million American adults.
"It was not previously known to this degree of detail and scale how viral reactivation might associate with COVID severity and outcome."
Dr. Ofer Levy, Boston Children's Hospital
Outside researchers cautioned against reading too much into the association. Dr. William Schaffner of Vanderbilt University, who was not involved in the study, noted that the findings point to a correlation rather than a proven cause of lingering illness.
"The authors carefully do not attribute any disease, including long COVID, to the reactivated viruses."
Dr. William Schaffner, Vanderbilt University Medical Center
The study population was limited to patients sick enough to be hospitalized, so it remains unclear whether milder COVID-19 cases trigger similar viral reawakening. The research team, coordinated in part by Dr. Joann Diray Arce, says the next step is determining whether measuring these reactivated viruses early in an infection could help identify patients at higher risk of long COVID, potentially opening a path toward earlier monitoring or treatment.
