The Potential Role of Viral Persistence in the Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated not only with the development of acute disease but also with long-term symptoms or post-acute sequelae of SARS-CoV-2 (PASC). Multiple lines of evidence support that some viral antigens and RNA can persist for up to 15 months in multiple organs in the body, often after apparent clearance from the upper respiratory system, possibly leading to the persistence of symptoms. Activation of the immune system to viral antigens is observed for a prolonged time, providing indirect evidence of the persistence of viral elements after acute infection. In the gastrointestinal tract, the persistence of some antigens could stimulate the immune system, shaping the local microbiota with potential systemic effects. All of these interactions need to be investigated, taking into account predisposing factors, multiplicity of pathogenic mechanisms, and stratifying populations of vulnerable individuals, particularly women, children, and immunocompromised individuals, where SARS-CoV-2 may present additional challenges.