Severe COVID-19 linked to dormant virus flare-ups and disability

Severe COVID-19 may trigger dormant viruses and deepen long-term harm

A large study tracking adults hospitalized with COVID-19 adds weight to a concern that has shadowed the pandemic for years: the virus may not act alone. Researchers followed 1,154 adults hospitalized with COVID-19 cases of varying severity for a year and found that severe SARS-CoV-2 infection could reactivate viruses already lying dormant in the body, including Epstein-Barr virus, cytomegalovirus, herpes simplex virus and anelloviruses.

The findings, reported Aug. 5 in Nature and summarized by Live Science, suggest that some of the damage associated with severe COVID-19 and long COVID may come from a broader cascade of immune disruption. Rather than a single infection producing a single set of downstream effects, severe COVID-19 may create conditions in which latent viruses begin replicating again, potentially adding to inflammation and complicating recovery.

That idea matters because many of the viruses identified in the study are extremely common. Epstein-Barr virus is well known as the cause of mononucleosis, but it often remains in the body for life after infection. Cytomegalovirus and herpes simplex virus also commonly persist in a latent state. Anelloviruses are even more widespread and are found in the vast majority of people, though they have not been definitively shown to cause human disease.

What the researchers found

The investigators collected blood samples and nasal swabs from participants, along with lung fluid from patients who required ventilation. By following patients over a year, they were able to compare viral reactivation patterns with later health outcomes rather than only capturing a snapshot during acute illness.

The study found that nearly half of hospitalized COVID-19 patients experienced reactivation of at least one dormant virus. That alone is a notable signal of immune strain. Severe viral illness has long been known to destabilize immune control, but the scale of this study gives the pattern more weight, especially because it included patients with different levels of disease severity and continued tracking them well beyond discharge.

The most striking finding involved anelloviruses. While these viruses are common and poorly understood, the researchers linked their reactivation to persistent physical disability associated with long COVID. That does not mean the study proved anelloviruses are directly causing disability. But it does identify them as a potentially important biological marker, and possibly a contributor, in the long and uneven recovery some patients face after severe infection.

Anna Cliffe, an associate professor at the University of Virginia who was not involved in the work, told Live Science that the study was among the largest and most carefully done of its kind. She said the findings support a model in which severe COVID-19 wakes dormant viruses and those reawakened infections may add to the inflammation that makes the disease worse.

Why latent viruses matter

Latent viruses are a defining feature of human biology. Many infections do not fully leave the body after symptoms fade. Instead, they persist silently, usually kept in check by the immune system. Problems arise when that control weakens. Severe illness, immune suppression and major inflammatory stress can all create opportunities for these pathogens to resurface.

In the case of COVID-19, that possibility has drawn sustained interest because long COVID does not look the same in every patient. Some people struggle mainly with fatigue and reduced exercise capacity. Others experience neurological symptoms, immune abnormalities or lasting organ effects. If latent virus reactivation is part of the picture, it could help explain why recovery patterns vary so widely and why some patients remain impaired long after the original infection resolves.

The study does not settle that question. It does, however, strengthen the case that clinicians and researchers should look beyond SARS-CoV-2 alone when trying to understand prolonged disability after hospitalization. A person recovering from severe COVID-19 may also be dealing with the biological effects of other viruses that have been pushed back into activity.

Implications for treatment and research

One practical consequence of the study is that it could shift attention toward monitoring viral reactivation more systematically in severe COVID-19 patients. If doctors can identify which latent viruses have reactivated and when, they may be able to better predict who is at greater risk of prolonged recovery problems.

The findings also point to new therapeutic questions. Study co-author Esther Melamed told Live Science that if the results involving anelloviruses are validated, there would be greater urgency around understanding those viruses and developing antivirals for them. That is a significant statement because anelloviruses have largely sat outside the center of mainstream drug development, in part because they have not been firmly tied to human disease.

Before any treatment changes, replication will be essential. Researchers will need to determine whether the association between anellovirus reactivation and physical disability holds up in other patient groups and whether reactivation is driving harm, merely reflecting immune dysfunction, or both. They will also need to test whether antiviral interventions, if available, actually improve outcomes.

Even with those uncertainties, the study gives long COVID research a more specific biological lead. Public discussion around long COVID has often been dominated by symptoms, patient experience and broad hypotheses about inflammation or autoimmunity. Those remain important, but this work adds a measurable viral dimension that can be tracked and tested.

A wider view of post-COVID recovery

The broader lesson is that severe COVID-19 may leave behind a more complex biological footprint than acute respiratory infection alone would suggest. For hospitalized patients, especially those with the most serious disease, recovery may depend not only on clearing SARS-CoV-2 but also on how the immune system regains control over other viruses that had long been dormant.

That insight could influence how researchers design follow-up studies, how hospitals monitor survivors of severe infection and how public health officials think about the lasting burden of COVID-19. The pandemic’s acute emergency phase may have passed, but the science of its long-term effects is still evolving. Studies like this one show that the aftershocks can involve hidden viral activity inside the patient as much as the original virus that put them in the hospital.

• The study followed 1,154 adults hospitalized with COVID-19 for one year.
• Nearly half experienced reactivation of at least one dormant virus.
• Anellovirus reactivation was linked to persistent physical disability associated with long COVID.

This article is based on reporting by Live Science. Read the original article.