Persistent Viral Reservoirs in Post-COVID Patients: Current Evidence and Clinical Implications

The COVID-19 pandemic has led to an unprecedented global health crisis, with millions recovering from acute infection but experiencing lingering symptoms, collectively referred to as post-acute sequelae of COVID-19 (PASC), or “long COVID.” While the precise mechanisms underlying long COVID remain elusive, one hypothesis gaining traction is the persistence of viral reservoirs in various tissues. Despite evidence of viral RNA and proteins detected in post-acute patients, the concept of viral reservoirs in the context of long COVID remains a subject of debate. This review explores the current scientific evidence for the existence of persistent SARS-CoV-2 in human tissues beyond the acute infection phase, focusing on the molecular mechanisms by which the virus may evade immune surveillance. We examine the role of immune dysregulation, chronic inflammation, and viral persistence in tissues such as the lungs, heart, brain, and gut. Additionally, we explore how these persistent viral elements may be associated with ongoing symptoms in long COVID and discuss the biological plausibility of these links. Finally, we discuss the clinical implications of viral persistence in post-COVID care, potential therapeutic strategies, and the need for further research to resolve the open questions surrounding this phenomenon.