Most people become infected with a virus at some point in their lives, be it one that causes the flu or one that causes the common cold. Usually, our bodies can fully clear them out. But some stick around, sleeping in the body until something reawakens them. The herpesvirus that causes chickenpox, for instance, can later lead to shingles
Now, researchers have found that Covid-19 might be one of those triggers. Out of more than 1,000 unvaccinated patients who were hospitalized with the respiratory illness, nearly half experienced a reactivation of dormant viruses, and some were associated with more severe Covid-19 or long Covid. The findings, published in the journal Nature on August 5, provide a better understanding of the connections and could help pave the way for new medicines
“The next step is determining whether identifying and treating reactivated viruses can improve outcomes for patients with acute Covid-19 and long Covid,” says study co-author Esther Melamed, a neuroimmunologist at the University of Texas at Austin, in a statement
Researchers have noticed some links between Covid-19 and certain viruses that stay in the body. Those include connections with cytomegalovirus (CMV), which can cause flu-like symptoms, and the Epstein-Barr virus, which causes mononucleosis—the “kissing disease”—and is associated with some cancers and autoimmune diseases. Both are herpesviruses, a common class of viruses that most people worldwide are carrying, even without symptoms
Past research on Covid-19 and viral reactivation has involved relatively few participants. So Melamed and colleagues examined 1,154 unvaccinated patients hospitalized with Covid-19 between May 2020 and March 2021. They had provided nasal swabs, blood samples and lung fluids during their hospital stays and for the following 12 months
Quick fact: How many Covid-19 cases?
There have been more than 779 million reported cases of Covid-19 reported worldwide, according to the World Health Organization
Analyses identified 11 reactivated viruses among nearly half the participants within 40 days of hospital admission. Some of the most common were CMV, Epstein-Barr virus and Herpes simplex virus type 1 (HSV1), which causes cold sores, although they followed different timelines. Epstein-Barr virus generally peaked early on, while CMV and HSV1 appeared about three weeks later. Additionally, anelloviruses—widespread viruses that are typically considered harmless—showed up around the time of hospital admission and declined several weeks later.
The “most striking” result is that these reactivations can happen in people with otherwise healthy immune systems, says Resia Pretorius, a biomedical scientist at Stellenbosch University in South Africa who was not involved in the study, to Max Kozlov at Nature. Many researchers suspect that weakened immune systems play a vital role in viral reactivation, so the new study challenges that assumption
What’s more, several observations hint that reawakened viruses might contribute to Covid-19 severity and length, the team found. Viral reactivation was associated with higher levels of certain proteins associated with inflammation, as well as increases in activated immune cells. Participants with reactivated herpesviruses also had fewer of certain types of molecules that help protect cells from oxidative stress, hinting that the reawakening might contribute to cellular damage
The findings about anelloviruses are particularly intriguing. Previously, their role in disease was debated because there was no evidence they directly caused illness, the authors write in the study. But the researchers found an association between the reactivation of anelloviruses and some symptoms of long Covid, such as fatigue and other physical difficulties
Additionally, reactivated anellovirus was associated with increased activity in certain white blood cells, hinting at an inflammatory response. That suggests these viruses “may not be entirely passive bystanders, but are actually contributing to immune dysregulation,” Melamed tells Science’s Catherine Offord
Still, the study doesn’t precisely answer whether anelloviruses cause long Covid or are just a sign of an overworked immune system, Danny Altmann, an immunologist at Imperial College London who wasn’t involved in the research, tells Nature
The new work also has several limitations, especially since it only included unvaccinated individuals infected early in the pandemic. “These are critically ill people that are sick with a very inflammatory virus,” says Timothy Henrich, an infectious diseases researcher at the University of California, San Francisco, to Science. It’s unclear how these findings would apply to a vaccinated individual who was infected with a more recent strain of Covid-19, for instance
Nevertheless, the researchers believe the work provides a new understanding of severe infections and possible treatment strategies, especially as Covid-19 continues to infect people
“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 ten million U.S. adults suffer from long Covid,” says study co-author Ofer Levy, a physician at Boston Children’s Hospital, in a different statement
“We need to help these patients recover with the best outcomes.”
