That makes anelloviruses an unlikely suspect in long COVID, a condition that has resisted a single explanation for six years.
Of the 11 viruses, anelloviruses were the ones most strongly associated with long-term physical disability and with long COVID.
“This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition,” Dr. Levy said.
“Although many no longer think of COVID being a problem, up to 50,000 Americans died of COVID in 2025-2026 respiratory season and some estimates suggest over 10 million U.S. adults suffer from long COVID,” he noted.
“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,” Dr. Levy said.
Most adults carry old viruses that stopped causing symptoms years ago.
Epstein-Barr, cytomegalovirus, and herpes simplex infect people when they’re young, and then go dormant for decades.
Severe COVID-19 reawakened 11 of those dormant viruses in hospitalized patients. The one most strongly linked to lasting illness belongs to a family few people have ever heard of.
Dr. Ofer Levy, a physician and researcher at Boston Children’s Hospital, was a site principal investigator on the work. He directs the hospital’s Precision Vaccines Program.
Viruses that live in almost everyone
The little-known family of viruses is called Anelloviridae. About 90 percent of people carry anelloviruses, usually without symptoms or any obvious harm.
Researchers still know little about what they do when they are active. Viruses that reawaken this way have been linked to autoimmune disease and other long-running conditions, which is the reason anyone was watching them.
That makes anelloviruses an unlikely suspect in long COVID, a condition that has resisted a single explanation for six years.
Of the 11 viruses, anelloviruses were the ones most strongly associated with long-term physical disability and with long COVID.
According to Dr. Levy, that connection matters.
“This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition,” Dr. Levy said.
Eleven viruses in 40 days
Dr. Levy’s team worked on a project funded by the National Institutes of Health that enrolled 1,154 hospitalized COVID-19 patients at 20 U.S. hospitals.
Fifteen research institutions took part. The experts set out to find blood markers that predict who gets sicker.
Infections the body cleared long ago can wake up when it comes under strain, so the team looked for those too. The researchers read the genetic material in patients’ samples for viruses that should have stayed dormant.
Within 40 days of admission they counted 11 that had not. Epstein-Barr, herpes simplex 1, cytomegalovirus and the anelloviruses were detected most often.
Joann Diray Arce leads the study’s clinical and data coordinating center at Boston Children’s Hospital and oversees data analysis for the Precision Vaccines Program.
“This is the largest and most comprehensive biomarker study of COVID-19, in which we followed more than one thousand patients, collected more than 200,000 samples, and generated more than 1 billion data points over the course of a year for this public resource,” Diray Arce said.
Inflammation woke the viruses
Doctors usually interpret this kind of reactivation as a sign that the immune system has been knocked down. Chemotherapy, transplant drugs, and untreated HIV all let old viruses return.
Dr. Levy’s team found something else in the patients’ blood. Epstein-Barr and cytomegalovirus reactivated in people whose immune defenses appeared to be working normally.
Those same patients had more inflammation throughout the body. The team concluded that the inflammation, rather than any weakening of the immune system, is what triggered the viruses.
That turns the usual explanation around. A body fighting hard can wake its own dormant infections.
The researchers argue that a doctor who knows which viruses have reawakened in a patient could anticipate the complications coming next and treat accordingly.
“Traditionally, viral reactivation is most associated with weakened immunity/immunocompromise. Here we noted viral reactivation in the context of strong inflammatory responses which is more unusual and might reflect distinct aspects of long COVID pathophysiology,” Dr. Levy told Earth.com in an exclusive interview.
Ten million Americans with long COVID
Dr. Levy said the scale of the problem has not shrunk the way public attention has.
“Although many no longer think of COVID being a problem, up to 50,000 Americans died of COVID in 2025-2026 respiratory season and some estimates suggest over 10 million U.S. adults suffer from long COVID,” he noted.
“We need to help these patients recover with the best outcomes.”
“Moreover, sooner or later, there may be another coronavirus pandemic, which means we need to learn all the lessons we can from COVID-19 to be better prepared.”
What the study cannot prove
No one has shown that a reawakened virus causes long COVID rather than arriving alongside it.
Everyone in this study was sick enough to be admitted to a hospital, so the millions who had mild COVID at home are not covered.
No one has traced what a reawakened anellovirus actually does inside a person either, because the family itself is so poorly understood.
“We need to learn more about Anelloviruses. Traditionally considered harmless, it is possible they may contribute to disease, and follow-up studies are needed to assess that possibility,” Dr. Levy told Earth.com.
“If so, then there may be rationale for developing antivirals against anelloviruses as well.”
Treatments for reactivated viruses
The team is now working out how the immune system answers these viruses across the course of a COVID infection.
The researchers now want to identify treatments that can control these reactivated viruses and determine when to give them, since timing could be critical to whether an intervention works.
“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,” Dr. Levy said.
The full study was published in the journal Nature.
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