Which dormant viruses can reactivate during severe COVID-19? Researchers detected several viruses in hospitalized patients and are studying whether reactivation may worsen illness or contribute to long COVID.
Severe COVID-19 may reactivate viruses that have remained dormant in the body for years, according to a large study that could offer new clues about why some patients develop prolonged symptoms after infection. ()
Researchers found evidence of viral reactivation in nearly half of 1,154 people hospitalized with COVID-19. The viruses included Epstein-Barr virus, cytomegalovirus (CMV), herpes simplex virus 1 and several anelloviruses. The study was published in Nature.
Nearly Half of Hospitalized Patients Showed Viral Reactivation
The researchers analyzed blood samples and nasal swabs from 1,154 people hospitalized with COVID-19 between May 2020 and March 2021. They also examined lung fluid from a group of patients who required mechanical ventilation.
Within 40 days of hospital admission, the team detected signs that 11 different viruses had become active again. Nearly half of the patients showed evidence of reactivation of at least one chronic virus. These viruses are common. Epstein-Barr virus and CMV belong to the herpesvirus family and can remain in the body after the initial infection. Anelloviruses are also widespread and are generally considered harmless, although their role in human disease remains poorly understood.
Reactivation Was Linked to More Severe COVID-19
Patients with evidence of viral reactivation tended to have more severe COVID-19 and higher levels of proteins associated with inflammation. The findings also suggest that reactivation may not simply be caused by a severely weakened immune system. Epstein-Barr virus and CMV appeared to become active alongside increased inflammation, including in some people whose immune systems were otherwise functioning.
That challenges the usual assumption that dormant viruses mainly become active when the immune system is suppressed. However, the study cannot establish whether the reactivated viruses made COVID-19 worse or whether severe COVID-19 caused the viruses to reactivate. Researchers say that relationship needs to be investigated further.
One Virus Family May Be Linked to Long COVID
Anelloviruses produced one of the study’s most notable findings. Reactivation of these viruses was associated with physical difficulties and symptoms linked to long COVID, including persistent fatigue. Researchers also found signs of increased immune activity in patients with anellovirus reactivation.
The finding does not prove that anelloviruses cause long COVID. They could instead be a marker of the immune and inflammatory changes that occur during prolonged illness. Researchers say more work is needed to determine whether these viruses are actively contributing to long-term symptoms or simply appearing alongside them.
Different Viruses Became Active at Different Times
The study also found that viral reactivation did not happen at the same stage of COVID-19 for every virus. Epstein-Barr virus generally appeared earlier during hospitalization, while CMV and herpes simplex virus 1 tended to become detectable later, around three weeks after admission.
Anelloviruses were detected around the time of hospital admission and then declined over the following weeks. The different timelines suggest that viral reactivation may be part of a changing immune response during severe COVID-19 rather than a single event.
Could Reactivated Viruses Lead to New Long COVID Treatments?
The findings could eventually help researchers identify new treatment targets for people who remain unwell after COVID-19. If further research confirms that certain reactivated viruses contribute to inflammation or long-term symptoms, testing for viral reactivation could potentially help identify patients who may benefit from targeted treatment.
For now, there is not enough evidence to recommend treating dormant viruses as a standard approach to COVID-19 or long COVID. The researchers’ next step is to study how the immune system responds to these viruses and whether treating their reactivation can improve outcomes.
Can the Findings Apply to All COVID-19 Patients?
The study has several limitations. The patients were unvaccinated and were infected during the early phase of the pandemic, between 2020 and early 2021. It is therefore unclear whether the same pattern occurs in vaccinated people infected with more recent SARS-CoV-2 variants.
The participants were also hospitalized patients, meaning the findings cannot be assumed to apply to people with mild COVID-19. Still, the size of the study makes it one of the more detailed investigations into viral reactivation during COVID-19. The results add another possible piece to the puzzle of severe and prolonged COVID-19 and raise the question of whether viruses already present in the body can influence how some people respond to SARS-CoV-2 infection.
References:
- Virus reactivation in acute and long COVID-19 – (https://www.nature.com/articles/s41586-026-10740-z)
Source-Medindia