A severe bout of Covid-19 can wake up a slew of dormant viruses hiding inside the body, according to an analysis of more than 1 000 people admitted to hospital with the disease, reports Nature.
The researchers said this reactivation of pathogens is linked to especially intense bouts of Covid-19 and to the development of long Covid.
If further research reveals that reactivated viruses can cause people to become seriously ill, it could open the door to new treatments for Covid-19 and even long Covid, said Esther Melamed, a physician-scientist who studies neuroimmunology at the University of Texas and is a co-author of the analysis.
Although the study didn’t dive into how Covid-19 prompts viruses to reawaken, Melamed said that the disease “probably induces the stress that triggers the reactivations, and then these reactivations further amplify the inflammation” caused by Covid-19.
In these cases, she added: “Covid is not really acting on its own.”
The viruses inside
Nearly everyone is infected by a variety of viruses throughout their childhood and adolescence. A handful of these pathogens are never fully cleared from the body. Instead, they hide quietly inside cells for a lifetime, kept in check by a healthy immune system.
Researchers have seen hints that these bystander viruses are reactivated in people with long Covid. So Melamed and her colleagues studied the situation systematically, collecting blood, nasal swabs and lung fluids from people hospitalised with Covid-19 in 2020 and early 2021.
Nearly half of them experienced a reactivation of common viruses lurking in their bodies, the researchers found. These pathogens included herpes viruses such as cytomegalovirus and Epstein–Barr virus, which causes glandular fever (mononucleosis), as well as anelloviruses, which are typically harmless and don’t cause symptoms.
More than 90% of the global adult population has been infected with at least one of these pathogens.
The team found that these viruses do not reawaken all at once after a person contracts the coronavirus SARS-CoV-2. Instead, different viral families reactivate on their own timelines. Epstein–Barr virus and anelloviruses tend to surge early during a bout of Covid-19, peaking shortly after hospital admission.
By contrast, cytomegaloviruses and herpes simplex viruses emerge around three weeks later, mainly in the respiratory system.
“The most striking result is that this reactivation happens even in people with otherwise healthy immune systems,” said Resia Pretorius, a physiologist at Stellenbosch University.
Some scientists had thought that a reawakening of viruses could happen only in people with a weakened immune system, such as those with HIV. “But this study overturns that assumption,” she added.
Some people included in the study were receiving immunosuppressive drugs during their hospital stay for various conditions. However, this didn’t make them any more likely to experience virus awakenings than those who were not taking such medication. This suggests that the stress of a coronavirus infection alone can overload the immune system.
The study also adds credence to the theory that latent viruses are not bystanders to acute infections. Epstein–Barr virus, for example, has been linked to, and perhaps even drives, autoimmune conditions such as multiple sclerosis and lupus.
Not-so-innocent bystanders
The researchers tracked participants for a year after their initial infection and found a link between the reactivation of anelloviruses and the development of long Covid, in which debilitating symptoms last for months or even years after a SARS-CoV-2 infection.
But this study does not answer the fundamental question of whether these typically innocuous viruses are causing illness or whether they are simply an indicator of an exhausted immune system, said Danny Altmann, an immunologist at Imperial College London.
To ensure that these health signals weren’t just a by-product of a severe coronavirus infection, the researchers compared their participants with a control group of people in the hospital who did not experience viral awakenings. They found that those with reactivated viruses had increased bodily inflammation, elevated immune-cell activity and more cellular damage by comparison.
The knowledge that SARS-CoV-2 acts as a catalyst for reawakening other viruses could lead to new treatment options, said David Putrino, a neuroscientist at the Icahn School of Medicine at Mount Sinai in New York City.
Instead of targeting only SARS-CoV-2 with medications, clinicians could aim existing antiviral therapies at the reawakened viruses, he said.
Putrino and his colleagues have now launched a phase 2 clinical trial for long Covid, which will test antivirals that target herpesviruses.
Altmann added that these findings should compel scientists to study dormant viruses that have long been thought of as innocuous or separate from acute respiratory illnesses.
People who have a type of herpesvirus that causes cold sores, for example, spend their lives going through reactivation and latency as the sores pop up and disappear, he noted. “We’ve never tried to map the consequences of these cycles, and this study shows why such work is essential.”
Study details
Virus reactivation in acute and long Covid-19
Cole Maguire, Jing Chen, Nadine Rouphael et al.
Published in Nature on 5 August 2026
Abstract
Chronic viral infections are ubiquitous in humans, with individuals carrying multiple viruses that can reactivate during physiological stress, including severe illness. Notably, SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein–Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in Covid-19 remain incompletely understood. Here, leveraging multi-omic longitudinal data from 1,154 hospitalised patients with Covid-19 from the Immunophenotyping Assessment in a Covid-19 Cohort (IMPACC) study, we reveal significant reactivation of Herpesviridae and Anelloviridae during acute Covid-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes. Although our results do not establish causation between virus reactivation and clinical outcomes, we highlight the prevalence of chronic viral reactivation during acute Covid-19 and long Covid. Our findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, we demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with long Covid. 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.
Nature article – Virus reactivation in acute and long Covid-19
Nature article – Covid can wake up a slew of dormant viruses inside you
See more from MedicalBrief archives:
‘Zombie’ cells the link between ME/CFS and long Covid – Stellenbosch study
Covid, flu can wake up ‘sleeping’ cancer cells – global study
Ongoing challenge to understand – and treat – long Covid