PANDAS/PANS in the COVID-19 Age: Autoimmunity and Epstein-Barr Virus Reactivation as Trigger Agents?

Abstract

COVID-19 impacted the entire world's population, frequently resulting in long-lasting neuropsychiatric complications. Furthermore, social distancing, lockdowns and fear for one's personal health worsen individual psychological wellbeing, especially in children and adolescents. Herein, we discuss the results of studies that specifically reported data about the impact of the COVID-19 pandemic or infection on children with Pediatric Acute-Onset Neuropsychiatric Disorders (PANS). Furthermore, we present the cases of five adolescents with PANS whose symptomatology increased following SARS-CoV-2 infection. What emerged from this study was that COVID-19 resulted in the exacerbation of obsessions, tics, anxiety and mood symptoms and decreased wellbeing. Moreover, new symptoms, as well as new PANS cases, are reported to have arisen after COVID-19 infection. Here, we hypothesize that the pathogenic mechanisms of silent viruses, such as the Epstein-Barr virus, are related to neuroinflammation, immune responses and reactivation, with additional roles played by social-isolation-related inflammatory processes. The discussion of PANS, which represents a model of immune-mediated neuropsychiatric manifestations, is particularly relevant, with the aim of uncovering the mechanisms that lead to neuropsychiatric Post-Acute COVID-19 Syndrome (PACS). Prospects for future studies and treatment implications are discussed.

Keywords: COVID-19; PANDAS; PANS; immunology; neuroinflammation.

Figure 1

The hypothesized mechanism of the effects of COVID-19 infection on PANS. COVID-19, as well as social isolation related to the pandemic, could have triggered an immune response which led to a reactivation of silent viruses and to aberrant inflammation, which could target the cortico-striatal networks. Considering the involvement of these circuits in the symptomatology of PANS and further disruption caused by the phenomena elicited post-COVID, PANS patients could have experienced an exacerbation of their symptoms.