A new study published in the journal Nature reveals that COVID-19 can awaken dormant viruses that have been lying quietly inside the human body for years, even in people who were otherwise healthy before falling ill with the virus. The findings suggest an unexpected consequence of severe COVID-19 infection that could reshape how physicians understand and treat both acute cases and the long-lasting condition known as long COVID.
Researchers at the University of Texas at Austin studied more than 1,100 hospitalized COVID-19 patients and found that nearly half had at least one dormant virus reactivate during their infection. The viruses that sprang back to life included Epstein-Barr virus, which causes mononucleosis, as well as other members of the herpes family that typically remain dormant in the body for life after initial infection.
The research was conducted as part of a larger study involving 15 biomedical research institutions across the United States. The patients in the study were hospitalized, unvaccinated, and mostly infected early in the pandemic between May 2020 and March 2021. Researchers collected samples from blood, nasal passages, and from the lungs of patients on ventilators. Participants were followed during their hospital stays and for up to a year after discharge.
One of the most striking findings was that viral reactivation occurred frequently in people who had been healthy before developing COVID-19, rather than being limited to patients with suppressed immune systems as previously assumed. Those whose dormant viruses reactivated were more likely to suffer severe illness, spend extended time in the hospital, develop serious complications, and die.
“This finding suggests that COVID-19 may not always act as a single viral infection and may disrupt the body’s internal ecosystem of dormant viruses,” said Cole Maguire, the study’s lead author, who is now a second-year medical student at the University of Texas at Austin’s Dell Medical School.
The researchers detected 11 different reactivated viruses within the first 40 days of hospital admission. The most commonly reactivated viruses were Epstein-Barr virus, herpes simplex virus-1, cytomegalovirus, and Anelloviridae, a poorly understood family of viruses that typically remain dormant in about 90 percent of the population. Notably, reactivation of Anelloviridae was strongly associated with long-term physical disability and long COVID.
A particularly important finding involved the mechanism of reactivation. In analyzing blood samples, researchers discovered that Epstein-Barr virus and cytomegalovirus appeared to reactivate in response to inflammation rather than immune system suppression. This suggests that the intense inflammation from severe COVID-19 may trigger the dormant viruses to spring back to life, potentially creating a cascade of additional immune complications.
The study does not prove that dormant viruses directly cause long COVID, but researchers say it provides compelling evidence that viral reactivation may play a significant role in the condition. “Tests already exist for several of the chronic viruses studied, and some viruses in the herpes family can be treated with existing antiviral drugs,” said Dr. Esther Melamed, the study’s principal investigator and a neuroimmunologist at the University of Texas at Austin. “The next step is determining whether identifying and treating reactivated viruses can improve outcomes for patients with acute COVID-19 and long COVID.”
Long COVID remains one of the most pressing mysteries of the pandemic. The condition can develop after a SARS-CoV-2 infection and leave patients struggling with a wide range of debilitating symptoms, including crushing fatigue, brain fog, and physical disability. Scientists still do not fully understand what causes long COVID, and there are currently no approved treatments.
The scale of long COVID is staggering. A study published in May estimated that roughly 1 in 6 people infected with SARS-CoV-2 develop long COVID, with many experiencing lasting health problems. Worldwide, more than 400 million people are believed to have experienced the chronic condition at some point, contributing to an estimated $1 trillion annual global economic impact tied to lost work and medical costs.
Researchers noted an important limitation of their study: the patients were hospitalized, unvaccinated, and mostly infected early in the pandemic with original coronavirus variants. It remains unclear whether the same patterns of viral reactivation occur with today’s dominant variants and in vaccinated populations with more mild infections.
Despite these limitations, the findings open a new direction for understanding how COVID-19 disrupts the body’s hidden viral ecosystem and could eventually lead to strategies for preventing some of its most devastating long-term complications. By revealing a potential mechanism that may contribute to severe outcomes and long COVID, the research provides scientists with a new avenue to pursue treatments that could address not just the immediate viral threat, but also the cascade of complications that emerges from dormant virus reactivation.