A new study published in Nature reveals that severe COVID-19 can reactivate dormant viruses like Epstein-Barr and Anelloviridae, linking this phenomenon to long COVID symptoms in nearly half of hospitalized patients.
Viral Reactivation and Long COVID Link
A study involving 1,154 hospitalized COVID-19 patients found that nearly half experienced reactivation of dormant viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Anelloviridae, which are typically kept in check by a healthy immune system. The research, led by institutions such as Boston Children’s Hospital and the University of Texas at Austin, identified a strong association between Anelloviridae reactivation and long COVID, a condition marked by persistent physical disabilities and fatigue. This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition,
said Levy.
The study, described as the largest and most comprehensive biomarker study of COVID-19, followed over 1,000 patients, collected more than 200,000 samples, and generated over 1 billion data points. Researchers detected 11 reactivated viruses within the first 40 days of hospitalization, with Anelloviridae and Herpesviridae families showing the highest prevalence. Anelloviridae, a poorly understood family of viruses that typically remains latent in about 90 percent of the population, showed a prominent association with long-term physical disability and long COVID,
the study noted.
Reactivation was not limited to immunosuppressed individuals, challenging prior assumptions. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and long COVID,
the researchers wrote. The findings suggest that inflammation, rather than immune suppression, may drive viral reactivation, with reawakened viruses potentially amplifying inflammation and worsening outcomes.
Mechanisms and Implications
Epstein-Barr virus (EBV) and Anelloviridae were among the earliest reactivated viruses, peaking shortly after hospital admission, while CMV and herpes simplex virus emerged later. The study found that reactivation was linked to higher levels of inflammatory proteins and changes in immune cell activity. The next step is determining whether identifying and treating reactivated viruses can improve outcomes for patients with acute Covid-19 and long Covid,
said study co-author Esther Melamed, a neuroimmunologist at the University of Texas at Austin.
Researchers also observed that viral reactivation was associated with severe complications, including a higher risk of death within one year for patients with CMV in the respiratory tract or EBV in the nasal cavity.
The study challenges the notion that viral reactivation is solely a consequence of immunosuppression. This finding demonstrates that reactivations occur frequently in apparently immunocompetent individuals during severe illness and in association with increased systemic inflammation,
the researchers stated.
Unanswered Questions and Future Directions
While the study provides critical insights, several questions remain unresolved. It is unclear whether the same patterns apply to newer variants or vaccinated individuals, as the research focused on patients infected early in the pandemic. The study also adds credence to the theory that latent viruses are not bystanders to acute infections,
said one researcher, emphasizing the need for further investigation into their role in chronic conditions.
Additionally, the study’s findings raise concerns about the long-term impact of viral reactivation. These are critically ill people that are sick with a very inflammatory virus,
said Timothy Henrich, an infectious diseases researcher at the University of California, San Francisco. We need to help these patients recover with the best outcomes.
The research also underscores the importance of understanding how dormant viruses interact with the immune system, particularly as new pandemics loom.
As the scientific community continues to explore these connections, the study highlights the complex interplay between viral reactivation, inflammation, and long-term health 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,
adds Levy.
