Pandemic is over but Covid-19 is not: Study says it may reactivate dormant viruses in your body

A severe COVID-19 infection may do more than trigger the immune system against SARS-CoV-2. A new study published in Nature has found that several viruses that normally remain dormant in the body can become transcriptionally active during severe illness.

Researchers analysed longitudinal data from 1,154 people hospitalised with COVID-19 across 20 US hospitals, examining more than 200,000 biological samples collected during hospitalisation and for up to a year afterwards. They found widespread reactivation of chronic viruses, particularly members of the Herpesviridae and Anelloviridae families.

The findings suggest that severe COVID-19 can be accompanied by a broader disruption of the body's existing viral landscape — a phenomenon the researchers describe as “dysvirosis.” Importantly, the study found that viral reactivation was associated with disease severity and inflammation, but did not prove that the reactivated viruses cause severe COVID-19 or long COVID.

Which dormant viruses were detected?

The researchers used RNA sequencing to look for actively expressed viral genetic material in blood cells, nasal swabs and, in ventilated patients, endotracheal aspirates.

Among the viruses detected were Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), HSV-2, human herpesviruses 6, 7 and 8, and several members of Anelloviridae.

The timing differed between viruses. EBV was detected early in the illness, while CMV and HSV-1 tended to reactivate later, with some respiratory detections peaking around three weeks after hospitalisation.

Overall, viral reactivation was detected in 47.9% of participants during the acute period, although most people with reactivation had only one virus detected.

One virus family stood out in long COVID

One of the study's most notable findings involved Anelloviridae, a group of viruses that are widespread in humans and whose role in disease remains poorly understood.

During the recovery period, Anelloviridae transcripts were significantly more common among participants in the study's physical-problems group, which included people reporting physical disability or fatigue. The association remained after researchers accounted for factors including age, sex, immunosuppressive medication and acute COVID-19 severity.

The researchers therefore suggest that Anelloviridae detection could potentially become a biological signature of persistent physical disability in some people with long COVID.

But that does not mean Anelloviridae has been shown to cause long COVID. The researchers explicitly note that the study cannot establish causation, and limitations included participant drop-out during the recovery period, which reduced the strength of the long-COVID analysis.

Reactivation may be tied to inflammation, not just weak immunity

The study also challenges a common assumption about why dormant viruses become active during serious illness.

The researchers found that viral reactivation frequently occurred in immunocompetent patients and was associated with increased systemic inflammation. EBV, CMV and HSV-1 were linked with changes in inflammatory cytokines and chemokines, including IL-6, IL-10, CXCL10, CXCL11 and IL-18.

This suggests that inflammation accompanying severe COVID-19 may itself be part of the environment in which some dormant viruses become active.

The big question researchers still cannot answer

The study provides evidence of an association between viral reactivation, severe COVID-19 and some long-term outcomes. But it does not establish whether the reactivated viruses are drivers of disease, consequences of severe illness, or simply passengers caught up in the body's response.

The researchers say future studies will need to determine whether targeting viral reactivation could actually improve outcomes in acute COVID-19 or long COVID.

There is another important limitation: the participants were hospitalised, unvaccinated patients who were primarily exposed to ancestral SARS-CoV-2 strains. It remains unclear whether the same patterns occur with newer variants, vaccination or hybrid immunity, or in people with milder COVID-19.