Severe COVID-19 infection has been associated with the reactivation of multiple dormant viruses in people who were previously healthy, a large longitudinal study published in Nature finds. Researchers detected reawakening of Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV) and members of the anelloviridae family. Study authors report that persistent activity of anelloviruses correlated with a subset of patients who developed long-term physical disability following COVID-19.
The research followed 1,154 adults hospitalized with COVID-19, collecting serial blood, nasal swab and, for ventilated patients, lung fluid samples at multiple points across the first year after infection. Tests searched for viral RNA and immune markers; nearly half the cohort—550 of 1,148 patients with full data—showed evidence of at least one latent virus reactivating. The timing varied by pathogen: EBV and anelloviruses tended to appear early, while CMV and HSV often emerged later. The main findings were reproduced using samples from a Mount Sinai biobank.
Clinical evaluation linked lingering anellovirus activity with reduced capacity for everyday tasks and profound fatigue—features commonly grouped under long COVID. Reactivation occurred even in patients without known immune suppression. Investigators and outside experts note plausible biological mechanisms: severe infection may divert immune surveillance or produce inflammatory signals such as IL-1 and IL-6 that can trigger latent viruses to exit dormancy. The study also cites parallels in other high-stress settings where herpesviruses have resurfaced despite overall healthy participants.
The authors emphasise important limitations: detection of viral RNA indicates gene activity but does not always prove the presence of new infectious particles, and the observed associations do not establish causation. Independent scientists involved in commentary highlighted the study’s size and repeated sampling as strengths. Moving forward, researchers recommend prospective interventional trials to test whether antiviral therapies targeting reactivated viruses could change outcomes for patients with severe COVID-19 and those with persistent post‑infectious disability. The findings prompt renewed attention to understudied viral families and the need for targeted antiviral development.
