Severe COVID-19 Reactivates Dormant Viruses, Linked to Long COVID Physical Deficits

When severe COVID-19 strikes, it does more than attack the lungs. It wakes up viruses that have been sleeping in the body for years—dormant infections that the immune system normally keeps under control without a sound. A new study of 1,154 hospitalized COVID-19 patients reveals that this viral awakening happens even in people with healthy immune systems, and that some of these reactivated viruses linger long after recovery, potentially linked to the physical exhaustion and weakness that defines long COVID.

Researchers analyzed blood and respiratory samples from patients admitted to hospitals between May 2020 and March 2021, tracking them for up to a year after discharge. They used RNA sequencing to detect active viral transcripts—not just antibodies suggesting past infection, but evidence of viruses actively replicating. What they found was striking: herpes simplex virus, cytomegalovirus, Epstein-Barr virus, and a family of viruses called Anelloviridae all flared up during acute COVID-19 infection. These are viruses most people carry quietly in their bodies, held in check by a functioning immune system. Severe COVID-19 disrupted that balance.

The pattern varied by virus and by where researchers looked. Epstein-Barr virus appeared early in blood samples, then gradually faded. Anelloviridae remained stubbornly present in blood cells, declining slowly over weeks. Cytomegalovirus and herpes simplex showed up later, primarily in respiratory samples. The viruses that reactivated correlated directly with how sick patients became. Those with cytomegalovirus, Epstein-Barr, or herpes simplex transcripts in their respiratory or nasal samples were more likely to die within a year. Patients with these viral reactivations also experienced more severe complications: pneumothorax, shock, blood clots, kidney failure, liver damage, and infections that spread through the bloodstream.

What makes this finding unsettling is that it challenges the long-held assumption that dormant viruses only reactivate in people whose immune systems are already broken—transplant recipients, cancer patients on chemotherapy, people with HIV. Here, the reactivation happened in immunocompetent individuals, people whose immune systems should have been working normally. Only 17 percent of those with Anelloviridae reactivation were even taking immunosuppressive medications. The virus itself—SARS-CoV-2—appeared to overwhelm the immune system's ability to keep these chronic infections in check, at least temporarily.

But the story extends beyond the acute hospital stay. When researchers looked at samples collected months later, during the recovery phase, Anelloviridae transcripts were still detectable. And here is where it connects to long COVID: patients who had persistent Anelloviridae in their blood during convalescence were significantly more likely to report physical deficits—the kind of persistent weakness, fatigue, and reduced physical capacity that characterizes long COVID. This association held even after accounting for age, sex, how sick they had been initially, and whether they were on immunosuppressive drugs.

The researchers are careful to note they have not proven causation. Anelloviridae reactivation might cause the physical deficits, or it might simply be a marker of something else happening in the body—a sign of ongoing immune dysregulation or tissue damage. The study cannot say which. What it does show is a correlation strong enough to suggest a new avenue for understanding why some COVID-19 survivors struggle with persistent physical symptoms while others recover fully.

The implications are practical. If future studies confirm these findings, doctors could test hospitalized COVID-19 patients for reactivated chronic viruses using standard PCR testing, then use those results to identify who is at highest risk for severe complications or long-term disability. It would be a form of personalized medicine born from understanding the virus's collateral damage—not just what SARS-CoV-2 does directly, but what it awakens in the body. The authors caution, though, that their study included only unvaccinated patients hospitalized with ancestral COVID-19 strains. Whether these patterns hold in vaccinated populations, in milder infections, or against newer variants remains unknown. The work is preliminary, but it points toward a more complete picture of how severe COVID-19 leaves its mark.