Study Finds Dormant Viruses Reactivate During COVID-19

Researchers who studied 1154 patients hospitalized with COVID-19 found that nearly half experienced reactivation of dormant viruses, including Epstein-Barr virus (EBV), HSV-1, cytomegalovirus (CMV), and viruses in the Anelloviridae family, according to a study published in Nature.¹

The findings, drawn from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study across 20 US hospitals, suggest reactivation is driven by inflammation rather than immune suppression and that one virus family was linked to long-term physical disability among individuals with long COVID. Collaborators on the study described it as the largest and most comprehensive biomarker study of COVID-19 to date.²

Study Draws on Multiomic Data From More Than 1000 Patients

The IMPACC cohort enrolled 1154 patients hospitalized with COVID-19 across 20 US hospitals between May 2020 and March 2021. All participants were vaccine-naive at enrollment. Investigators, led by corresponding author Esther Melamed of Dell Medical School at the University of Texas at Austin, followed participants for up to 12 months and collected blood, nasal, and, in mechanically ventilated patients, endotracheal samples at up to 10 visits per participant.¹

Fifteen biomedical research institutions collaborated on the analysis, which incorporated more than 200,000 samples and over 1 billion data points, according to Boston Children's Hospital, one of the participating sites.²

Investigators used RNA sequencing, cytometry by time of flight, antibody titers, cytokine profiling, and mass spectrometry-based proteomics and metabolomics to detect and characterize reactivation of viruses from the Herpesviridae and Anelloviridae families. Nearly half of participants, 47.9% (550 of 1148), had detectable transcripts from at least 1 chronic virus within the first 40 days of hospitalization, most often EBV, HSV-1, CMV, or Anelloviridae.¹

Each virus followed a distinct timeline. EBV reactivated early and declined gradually, Anelloviridae remained at a constant frequency until around day 20 before slowly declining, and HSV-1 and CMV reactivated later, around day 22, primarily in respiratory samples.¹

Findings Challenge Assumptions About Immunosuppression

Reactivation of EBV and CMV has traditionally been attributed to immunosuppression, but the study found otherwise. Only 17.4% of participants with Anelloviridae reactivation were taking immunosuppressive medications, and reactivation was not significantly associated with steroid or remdesivir use. Investigators concluded that inflammation associated with severe COVID-19, rather than a suppressed immune system, was driving much of the viral reactivation observed, even among immunocompetent patients.¹

Reactivation was also associated with disease severity and, among the most critically ill patients, with mortality. Nasal and endotracheal CMV, nasal EBV, and nasal HSV-1 were all significantly associated with death in this group. CMV reactivation detected in blood cells was additionally linked to complications including bacteremia, pulmonary vascular disease, renal complications, shock, and stroke, while EBV reactivation was associated with liver failure and concurrent infections.¹

"This association with long COVID is an interesting finding as millions around the world suffer from this chronic condition," Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children's Hospital, said in a news release.²

Anelloviridae Reactivation Linked to Long COVID Disability

Among the study's long COVID findings, Anelloviridae transcripts detected during convalescence were significantly associated with a patient-reported outcome group characterized by physical disability and fatigue, independent of sex, age, immunosuppressive medication use, and severity of acute illness.¹

Anelloviridae and enteroviruses were the viruses most frequently detected during the convalescent period, and Anelloviridae showed a consistent gene expression signature between the acute and convalescent phases. The investigators cautioned that their results do not establish that viral reactivation causes these outcomes, though they noted the pattern may reflect ongoing inflammation.¹

"This is the largest and most comprehensive biomarker study of COVID-19," Joann Diray-Arce, PhD, lead of the Precision Vaccines Program's Data Management and Analysis Core at Boston Children's Hospital, said in the news release.²

The findings were replicated in an external whole-blood sequencing cohort, which showed similar reactivation timelines for EBV, CMV, and Anelloviridae over the first 40 days after symptom onset.¹

Implications for Pharmacists

The research adds to a broader body of work on latent viruses such as EBV, which infects more than 90% of the global population and can reactivate in response to physiological stress, including infection.³

EBV reactivation has separately been linked to persistent fatigue and comorbid myalgic encephalomyelitis/chronic fatigue syndrome in patients with long COVID, prompting some clinicians to suggest that blood testing for reactivated latent viruses could eventually become part of a standard long COVID workup to guide more targeted treatment.³

For pharmacists, the findings underscore the importance of monitoring patients recovering from severe COVID-19. More than 10 million US adults are currently estimated to be living with long COVID, and up to 50,000 Americans died of COVID-19 during the 2025-2026 respiratory season, according to Boston Children's Hospital.²

Because CMV reactivation was linked to renal complications and Anelloviridae to physical disability in long COVID, pharmacists involved in post-hospitalization care may want to remain attentive to patients presenting with unexplained fatigue, cognitive symptoms, or changes in kidney function following severe COVID-19 illness and to flag these findings for further clinical workup.

REFERENCES

1. Maguire C, Chen J, Rouphael N, Morse BA, Melamed E, et al. Virus reactivation in acute and long COVID-19. Nature. 2026. doi:10.1038/s41586-026-10740-z

2. Boston Children's Hospital. COVID-19 awakens dormant viruses — and one is linked to long COVID. News release. Boston Children's Hospital. August 14, 2026. Accessed August 17, 2026. https://www.sciencedaily.com/releases/2026/08/260814011034.htm

3. RTHM Medical Team. Viral reactivation and long COVID. RTHM. September 14, 2025. Accessed August 17, 2026. https://www.rthm.com/resources/blogs/viral-reactivation-and-long-covid