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Viral persistence, reactivation, and mechanisms of Long COVID

Chen, B; Julg, B; Mohandas, S; et al., eLife

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Published

May 2023

Journal

eLife

Abstract

The COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has infected hundreds of millions of individuals. Following COVID-19 infection, a subset can develop a wide range of chronic symptoms affecting diverse organ systems referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. A National Institutes of Health-sponsored initiative, RECOVER: Researching COVID to Enhance Recovery, has sought to understand the basis of long COVID in a large cohort. Given the range of symptoms that occur in long COVID, the mechanisms that may underlie these diverse symptoms may also be diverse. In this review, we focus on the emerging literature supporting the role(s) that viral persistence or reactivation of viruses may play in PASC. Persistence of SARS-CoV-2 RNA or antigens is reported in some organs, yet the mechanism by which they do so and how they may be associated with pathogenic immune responses is unclear. Understanding the mechanisms of persistence of RNA, antigen or other reactivated viruses and how they may relate to specific inflammatory responses that drive symptoms of PASC may provide a rationale for treatment.

Authors

Benjamin Chen, Boris Julg, Sindhu Mohandas, Steven B Bradfute; RECOVER Mechanistic Pathways Task Force

Keywords

PASC; Reactivation; SARS-CoV-2; epidemiology; global health; immunology; inflammation; long COVID; viral persistence

Short Summary

This paper summarizes some work of the RECOVER Mechanistic Pathways Task Force. This group does research on what happens in body systems when people have Long COVID. In this study, the authors reviewed existing research about why and for how long SARS-CoV-2, the virus that causes COVID-19, stays in the body. The authors also reviewed research on whether SARS-CoV-2 might become dormant (inactive) and then reactivate later as part of its natural lifecycle. They discuss whether the amount of time the virus stays in the body, also known as the “persistence” of the virus, could be related to whether or not people develop Long COVID. They also describe what is known so far about this topic, what we still need to find out, and the types of research studies that may help answer these questions.  

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