Virus reactivation in acute and long COVID-19
Chronically infecting viruses are prevalent in the general population, with individuals carrying 8–12 viruses at any given time1. These viruses are generally innocuous and typically do not cause infectious symptoms. However, emerging evidence suggests that their reactivation may contribute to autoimmune diseases, malignancies and chronic fatigue syndrome1,13,14,15. Additionally, Herpesviridae such as EBV and CMV commonly reactivate in severe infections (for example, malaria or pneumonia) and sepsis18,33,34 and have more recently been implicated in long COVID4,22,35. Thus, there is an urgent need to understand how chronically infecting viruses reactivate in COVID-19 and develop strategies to combat their reactivation. Here we conducted a prospective, multi-omic analysis of 1,154 patients who were hospitalized due to COVID-19, which revealed widespread reactivation of chronic viruses from the Herpesviridae and Anelloviridae families. By integrating cellular and cytokine immunophenotyping, metabolomics and transcriptomics, our findings expand on the complex interplay between SARS-CoV-2 and chronic viral reactivation and provide a deeper understanding of the host immune response. Importantly, our findings demonstrate an association of viral reactivation with COVID-19 and long COVID outcomes. Despite prior studies evaluating viral reactivation in COVID-19 (refs. 2,3,4,5,6,7,22,23) and other infections18,33,34, the exact timing and rates of reactivation for different viruses have not been clearly...
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