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.

Microbes and Mental Illness: Past, Present, and Future

“…The proposed mechanisms for PASC [ 433 , 434 , 435 , 436 , 437 , 438 ] include persistent reservoirs of pathogens or pathogen remnants (e.g., SARS-CoV-2 structural proteins such as spike protein or spike protein fragments such as the S1 subunit); the development of autoimmunity due to molecular mimicry between pathogen and host proteins; the reactivation of other latent pathogens; dysbiosis from SARS-CoV-2–host-microbiome interactions; and resultant organ system or tissue damage from the infection and associated immunopathology, including vasculopathy, coagulopathy, and clotting issues. These potential contributors may act independently or in combination to cause persistent symptoms.…”

“…Since the original description of PANDAS, it has subsequently become recognized as part of a broader category called pediatric acute-onset neuropsychiatric syndrome (PANS) [ 243 , 498 ]. Unlike PANDAS, the name PANS recognizes that the neuropsychiatric and other manifestations of this syndrome can be triggered by not just streptococcal infections but also a variety of other infections [ 243 , 499 ] (e.g., Mycoplasma [ 263 ], Borrelia (Lyme disease) [ 500 ], Bartonella [ 162 ], SARS-CoV-2 [ 82 , 425 , 437 ]), as well as, potentially, non-infectious triggers, such as environmental exposure to toxins or other inducers of inflammatory reactions [ 498 , 501 ]. As originally defined, the primary symptoms of PANS are the sudden onset of obsessive–compulsive symptoms or restricted eating behaviors.…”

Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children

“…If chronic or recurrent EBV infection affects epithelial cells, systemic lupus erythematosus and Sjögren’s syndrome can occur, and when B cells are infected, chronic arthritis, multiple sclerosis, and other diseases can occur. These secondary autoimmune diseases present as overlapping syndromes with clinical and biological manifestations expressed by specific autoantibodies (e.g., antinuclear antibodies and rheumatoid factors) that reflect epithelial and/or B-cell infection [ 148 , 149 , 150 , 151 , 152 ].…”