Severe COVID may reawaken dormant viruses, major study finds

Almost half of the patients hospitalised with COVID-19 in one of the largest studies of the disease so far had a long dormant virus stir back to life inside them, and the sicker they were, the more often it was happening.

The finding comes from research published in the journal Nature on 5 August 2026, with first author Cole Maguire and senior author Esther Melamed of Dell Medical School at The University of Texas at Austin.

The team followed 1,154 people admitted with COVID-19 at 20 hospitals across 15 American academic institutions between May 2020 and March 2021, with repeated sampling scheduled through the first year after admission.

The passengers everyone carries

Most people are carrying between eight and 12 chronic viruses at any moment without knowing it.

They were picked up at some point in life, they settled in for good, and they normally stay clinically quiet. Doctors have long known these viruses can stir during periods of physical strain, including surgery, severe sleep loss and critical illness, and earlier research has connected their reactivation to autoimmune disorders, certain cancers and long lasting fatigue syndromes.

Those are associations reported previously, not findings of this study.

What remained poorly understood was how often these viruses reactivate during one specific illness, when each of them appears, and how any of it relates to what happens to the patient.

Reading the virus, not the antibody

Earlier studies of this question mostly relied on antibodies, which show that the immune system met a virus at some point but not that anything is happening now.

This team looked instead for viral RNA transcripts, evidence that a virus's genes were actively switched on.

That is a much closer measure of viral activity than antibodies, though it does not by itself prove the virus was producing new infectious particles.

Nearly half of the participants, 550 out of 1,148 with usable samples, had at least one chronic virus detected this way in the first 40 days after admission. Most of them had only one.

The viruses turned up on their own schedules.

Epstein-Barr virus, the cause of glandular fever, was detectable in about one in four patients during the first eight days after admission, which suggests it may have begun stirring before some of them were sick enough to be hospitalised.

Cytomegalovirus and herpes simplex, the cold sore virus, arrived later and peaked around three weeks in, mostly in the nose and airway.

Anelloviruses, a family so common that some members live in 80 to 90 percent of people and whose role in human disease is still unsettled, stayed active for weeks before slowly fading.

Where the risk showed up

Reactivation tracked closely with how ill patients were. Among the most critically ill group, those who stayed in hospital beyond 28 days, certain patterns of viral detection went together with a higher chance of dying within a year of admission.

That applied to cytomegalovirus found in the nose or the airway, and to Epstein-Barr virus and herpes simplex found in nasal samples.

Different viruses came with different complications.

Cytomegalovirus in the blood was associated with bloodstream infection, kidney complications, stroke and shock. Epstein-Barr virus in the blood was associated with liver failure and a higher overall number of complications.

Months after discharge, the picture shifted. Anelloviruses, the least understood family in the study, were more common in the group of patients still reporting reduced physical function and fatigue, one of the recognised patterns of long COVID.

That association held after accounting for age, how sick the patient had been, and whether they were taking immune suppressing medicines.

A challenge to the standard explanation

The conventional assumption has been that dormant viruses reactivate mainly when the immune system is weakened, which is why the phenomenon is watched closely in transplant and cancer patients.

This study found something different.

Reactivation was common in patients with no sign of a compromised immune system, and it went together with high inflammation.

For the herpes viruses in particular, immune suppressing medication did not explain what the researchers saw, which points to other forces at work. ,

The findings suggest viral reactivation may matter well beyond the immunosuppressed patients in whom it has traditionally been recognised.

What the study cannot say

The authors are direct about the limit of their own work.

This was an observational study, so it cannot show whether the reawakened viruses worsened the illness, followed from it, or sat alongside it as part of the same process.

Severe illness, inflammation and the body's response could all be driving both at once. As the paper puts it, whether and how these reactivations contribute to clinical outcomes remains unknown.

There are further constraints. Everyone enrolled was unvaccinated against COVID-19 and infected with early strains of the virus, before widespread vaccination and later variants.

The long COVID analysis was weakened by heavy dropout during follow-up, particularly among the patients who had viral reactivation during the acute illness.

And the team analysed only blood cells, nasal swabs and airway samples from ventilated patients, so reactivation elsewhere in the body would have gone unseen.

Why it matters beyond one disease

The practical appeal is that hospitals would not be starting from scratch.

Quantitative PCR testing for the herpes viruses and for anelloviruses, including torque teno virus, is already established laboratory technology, and antiviral medicines exist for several of the herpes viruses.

What is missing is any evidence that detecting a reawakened virus, or treating one, changes what happens to the patient.

"This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition," said Dr Ofer Levy, director of the Precision Vaccines Program at Boston Children's Hospital and a site principal investigator on the study, in a news release from the hospital.

"Having new insight as to the molecular and viral associations with long COVID could point the way to better understanding and ultimately better diagnostics and treatments."

The wider relevance sits outside COVID-19 altogether.

The authors point to earlier evidence that herpes viruses such as Epstein-Barr and cytomegalovirus also reactivate during severe malaria, pneumonia and sepsis.

If reactivation turns out to be a general feature of severe illness rather than a quirk of one coronavirus, the same question would arise on wards far from the American hospitals where this study was done.

Nothing in this research tests that, because every participant was recruited in the United States.

For now the study expands understanding of viral reactivation without establishing any new standard for testing or treatment. Whether targeted detection or treatment improves recovery is the work that comes next.

Source

Maguire C, Chen J, Rouphael N, et al. Virus reactivation in acute and long COVID-19. Nature. 2026. doi:10.1038/s41586-026-10740-z