A study involving 1,154 hospitalized COVID-19 patients found that the virus reactivates dormant pathogens like Epstein-Barr and Anelloviridae, linking them to long COVID and severe outcomes, according to research published in Nature.
Researchers have uncovered a critical mechanism by which severe COVID-19 infections disrupt the body’s viral ecosystem, reactivating dormant viruses that may worsen symptoms and contribute to long-term health issues. The findings, published in Nature, reveal that nearly half of hospitalized patients experienced reactivation of viruses such as Epstein-Barr (EBV), cytomegalovirus (CMV), and Anelloviridae, with the latter strongly associated with long COVID and physical disability.
Reactivation Patterns and Viral Associations
The study, led by Boston Children’s Hospital and involving 15 biomedical institutions, tracked over 1,000 patients from 2020 to 2021, analyzing 200,000 biological samples. It found that nearly half of participants had at least one dormant virus reactivate during acute infection. Anelloviridae, a family of viruses present in 90% of the population, showed a significant link to long-term physical disability, while EBV and CMV were tied to more severe disease outcomes.
This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition,
said Dr. Ofer Levy, a lead researcher, in a statement. The study also noted that reactivation often occurred in immunocompetent individuals, challenging prior assumptions that such events only affect immunosuppressed patients.
Viral reactivation was detected in multiple compartments, including blood, nasal swabs, and lung fluids. Epstein-Barr and Anelloviridae peaked early in infection, while CMV and herpes simplex virus emerged later, primarily in the respiratory tract. The research highlighted that reactivation was linked to elevated inflammation markers and immune dysregulation, suggesting a complex interplay between SARS-CoV-2 and the body’s viral landscape.
Mechanisms and Immune System Impact
Researchers observed that reactivated viruses, particularly Anelloviridae, persisted during recovery, with some patients showing ongoing viral activity months after initial infection. This persistence was associated with symptoms like fatigue and reduced physical function, key features of long COVID.
We need to help these patients recover with the best outcomes,
said Levy, emphasizing the urgency of understanding these mechanisms. The findings suggest that targeting reactivated viruses could open new avenues for treating long COVID, with some researchers already exploring antiviral therapies in clinical trials.
Implications for Treatment and Future Pandemics
Researchers are now investigating whether antiviral treatments targeting herpesviruses could improve outcomes for long COVID patients. If future studies confirm a causal relationship, it could open the door to treating long-term aftereffects of COVID-19,
said Melamed.
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,
said Levy.
What Comes Next: Research and Policy Directions
While the study establishes a strong association between viral reactivation and long COVID, causation remains unproven. Researchers caution that further studies are needed to confirm these links and explore therapeutic strategies. Correlation doesn’t equal causation,
said Maria Laura Gennaro, a microbiologist at Rutgers Health, in a separate analysis.
This is the largest and most comprehensive biomarker study of COVID-19,
said Joann Diray Arce, lead of the study’s data coordinating center.
