Severe COVID-19 can awaken dormant viruses hidden in the human body, such as Epstein-Barr and cytomegalovirus, according to a study published in Nature.
How COVID-19 Triggers Hidden Pathogens
Most humans carry a collection of viruses that remain quiet for decades. These pathogens typically stay dormant, kept in check by the immune system or resting quietly in tissues after a primary infection earlier in life. But when a severe coronavirus infection takes hold, it can disrupt this internal ecosystem, effectively flipping the switch on long-dormant agents.
A major observational analysis examined blood samples, nasal swabs, and lung secretions from 1,154 individuals hospitalized with COVID-19. The project drew on data generated by the National Institutes of Health-funded Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) consortium, which brought together investigators from more than 15 universities and 20 U.S. hospitals from May 2020 to March 2021.
When researchers screened the samples for genetic material indicating active viral replication, they discovered that nearly half of the hospitalized participants experienced a reactivation of at least one chronic virus.
“Traditionally, viral reactivation is most associated with weakened immunity/immunocompromise. Here we noted viral reactivation in the context of strong inflammatory responses which is more unusual and might reflect distinct aspects of long COVID pathophysiology.”
Dr. Ofer Levy, physician and researcher at Boston Children’s Hospital
Temporal Dynamics of Eleven Reawakened Viruses
The study tracked 11 distinct reactivated viruses within the first 40 days after hospital admission. These pathogens did not all wake up at once. Instead, different families of viruses followed distinct timelines as the acute illness progressed.
Epstein-Barr virus and members of the Anelloviridae family tended to appear early in the course of infection. Among critically ill patients, the detection of cytomegalovirus, Epstein-Barr virus, or herpes simplex virus 1 in the respiratory tract was also associated with a greater likelihood of dying within the first year following admission.
| Virus Family / Pathogen | Timing of Detection | Observed Clinical Associations |
|---|---|---|
| Epstein-Barr Virus (EBV) | Early in infection, near hospital admission | Reactivated by systemic inflammation; tied to severe outcomes |
| Anelloviridae | Early detection, persisting into convalescence | Strongly linked to long COVID, chronic fatigue, and physical disability |
| Cytomegalovirus (CMV) | Later stage, peaking around three weeks | Linked to pneumothorax, kidney complications, stroke, and shock |
| Herpes Simplex Virus 1 (HSV-1) | Detected during acute and later stages | Associated with severe illness and mortality among critical patients |
Crucially, the viral reawakening was not restricted to individuals with preexisting immune deficiencies. Researchers at Dell Medical School at The University of Texas at Austin noted that the phenomenon frequently occurred in patients who had been healthy before developing COVID-19.
The Connection to Long COVID and Physical Disability
While the study did not definitively prove that reawakened viruses directly cause long-term illness, it established a statistical link between persistent viral activity and ongoing symptoms. In particular, researchers highlighted Anelloviridae, a poorly understood family of viruses carried by roughly 90 percent of people.
Patients who experienced persistent fatigue, cognitive dysfunction, and physical impairment months after acute infection were more likely to show ongoing anellovirus activity. This poorly understood viral family may contribute to the complex physical symptoms that frustrate millions of patients worldwide.
Study leaders emphasize that identifying these reactivated pathogens could eventually change clinical care. Because tests already exist for many chronic viruses—and some herpes-family viruses can be managed with existing antiviral drugs—future research will focus on whether screening and treating these internal flare-ups can improve recovery rates for both acute patients and those battling long-term syndromes.
