text: Implications of Innate Immunity in Post Acute Sequelae of Non Persistent Viral Infections Non persistent viruses classically cause transient acute infections triggering immune responses aimed at the elimination of the pathogen Successful viruses evolved strategies to manipulate and evade these anti viral defenses Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers In some patients however symptoms persist or new symptoms emerge beyond the acute phase Conditions resulting from previous transient infection are termed post acute sequelae PAS and were reported for a wide range of non persistent viruses such as rota influenza or polioviruses Here we provide an overview of non persistent viral pathogens reported to be associated with diverse PAS among them chronic fatigue auto immune disorders or neurological complications and highlight known mechanistic details Recently the emergence of post acute sequelae of COVID 19 PASC or long COVID highlighted the impact of PAS Notably PAS of non persistent infections often resemble symptoms of persistent viral infections defined by chronic inflammation Inflammation maintained after the acute phase may be a key driver of PAS of non persistent viruses Therefore we explore current insights into aberrant activation of innate immune signaling pathways in the post acute phase of non persistent viruses Finally conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed 