COVID-19 May Reactivate Dormant Viruses in the Body

Severe COVID-19 may reactivate dormant viruses that have remained hidden inside the body, according to a study of more than 1,000 people hospitalized with the disease.

Published today in Nature¹, the study links latent virus reactivation with more serious COVID-19 illness and an increased risk of developing long COVID.

If future research confirms that reactivated viruses contribute directly to severe disease or persistent symptoms, the findings could support new treatments for COVID-19 and long COVID, says Esther Melamed, a physician-scientist who studies neuroimmunology at the University of Texas at Austin and co-authored the analysis.

The study did not determine exactly how SARS-CoV-2 causes dormant viruses to become active. Melamed says that COVID-19 “probably induces the stress that triggers the reactivations, and then these reactivations further amplify the inflammation” caused by the infection. In such cases, she adds, “COVID is not really acting on its own.”

Which dormant viruses can reactivate after COVID-19?

Most people are infected with several viruses during childhood or adolescence. Some of these pathogens are never completely eliminated. Instead, they remain latent inside cells for years or even decades, usually controlled by a healthy immune system.

Four lessons COVID taught us about the immune system

Previous research has suggested that latent viruses may become active in people with long COVID. To investigate this relationship, Melamed and her colleagues analyzed blood samples, nasal swabs and lung fluids from people hospitalized with COVID-19 in 2020 and early 2021. Almost half of the participants showed signs that common viruses already present in their bodies had reactivated.

The reactivated pathogens included herpesviruses such as cytomegalovirus and Epstein–Barr virus, which causes glandular fever, also known as mononucleosis. The researchers also detected anelloviruses, which are generally harmless and do not typically cause symptoms. More than 90% of adults worldwide have been infected with at least one of these viruses².

The analysis found that latent viruses do not all reactivate at the same time after infection with SARS-CoV-2, the coronavirus that causes COVID-19. Instead, different virus families follow different timelines. Epstein–Barr virus and anelloviruses tend to increase early in the illness, reaching peak levels soon after hospital admission. Cytomegaloviruses and herpes simplex viruses, by contrast, generally appear about three weeks later, particularly in the respiratory system.

Could long COVID be linked to herpes viruses? Early data offer a hint

The “most striking” finding is that virus reactivation occurred even in people with otherwise healthy immune systems, says Resia Pretorius, a physiologist at Stellenbosch University in South Africa. Scientists had previously assumed that dormant viruses were most likely to reactivate in people with severely weakened immunity, including those with HIV. This study “overturns” that assumption, she says.

Some participants received immunosuppressive drugs during hospitalization for other medical conditions. However, they were no more likely to experience viral reactivation than participants who did not take these medications. The result suggests that the physiological stress caused by COVID-19 alone may be enough to disrupt immune control and allow latent viruses to become active.