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

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.

COVID-19 Related Distress in Gambling Disorder.

The COVID-19 pandemic has exerted a dramatic impact on everyday life globally. In this context, it has been reported that the lockdown and social distancing may have exerted an impact even on gambling behavior, not only by increasing gambling behavior in those affected by this disorder but even contributing to the occurrence of new cases. To explore such a possibility, we designed a cross-sectional web survey addressing a general population sample that lasted 3 weeks (March 23-April 20). Participants completed a survey including a demographic information section, a question regarding the presence of pathological gambling in the past and several questionnaires. These included the Perceived Stress Scale (PSS), the Kellner's Symptom Questionnaire (SQ), and the version of The Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS) that investigated the presence of gambling behaviors in the last week. The final sample was composed by 254 subjects (112 males, 44.1%; 142 females, 55.9%). According to PG-YBOCS total score, pathological gambling has been found in 23.6% (n = 60) of the sample (53 males, 88.3%; 7 females, 11.7%), which is a high frequency compared to that reported by the existing literature. Among gamblers, 20.9% (n = 53) reported both past and current problem gambling (they have been defined as "chronic gamblers"), whereas 2.8% (n = 7) did not report to use gambling platforms in the past but only in the last week (defined as "new gamblers"). Data analysis showed a statistically significant difference between gamblers and people who do not gamble in age but not in education, and higher level of perceived stress, distress, and hostility in both chronic and new gamblers compared to those who did not report gambling behavior. A consistent proportion of business owners and unemployed individuals reported problem gambling during the lockdown period.

Advances in problematic usage of the internet research - A narrative review by experts from the European network for problematic usage of the internet.

Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion. A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives. However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders.

Modulating neuroinflammation in COVID-19 patients with obsessive-compulsive disorder.

Exacerbation of symptoms of obsessive-compulsive disorder (OCD) during COVID-19 or new onset of the OCD symptoms resulting from COVID-19 infection is an understudied area of research. It is possible that increased proinflammatory immune status is associated with the onset of obsessive-compulsive symptoms in patients with COVID-19 and that targeted anti-inflammatory treatments for COVID-19 infection can mitigate the new onset of Obsessive-Compulsive (OC) spectrum symptoms. In this review, we cover OCD pathogenesis as related to COVID-19, summarize the impact of cytokines on behavior, and suggest that anti-cytokine treatments can help mitigate post-COVID-19 and new onset of the OC symptoms.

Presentation and management of anxiety in individuals with acute symptomatic or asymptomatic COVID-19 infection, and in the post-COVID-19 recovery phase.

COVID-19 is associated with neuropsychiatric complications, the most frequent one being anxiety. Multiple biological and psychosocial factors contribute to anxiety in COVID-19. Among the biological factors, stress, genetics, gender, immune system, resilience, anosmia, hypogeusia, and central nervous system infection with SARS-CoV-2 are key. Anxiety is a complication of COVID-19 that may exacerbate the infection course, and the infection may exacerbate anxiety. We present the mechanisms of anxiety in symptomatic or asymptomatic COVID-19. We discuss the presentation of anxiety in patients without or with prior psychiatric illness, and with co-morbidities. Timely diagnosis and management of anxiety in COVID-19 patients is important. Given the frequent complication of COVID-19 with Acute Respiratory Distress Syndrome and Intensive Care Unit stay, anxiety may be a long-term complication. We review the diagnostic tools for anxiety in COVID-19, and summarise pharmacologic and non-pharmacologic treatments. We provide recommendations for diagnosis, treatment, prevention and follow up of anxiety in COVID-19.Key pointsPatients with COVID-19 (symptomatic or asymptomatic) exhibit a high frequency of neuropsychiatric complications with highest percentage attributed to anxiety.Multiple biological and psychosocial risk factors for anxiety exist in COVID-19-ill individuals. Biological risk factors include stress, resilience, genetics, gender, age, immune system, direct infection of the central nervous system (CNS) with SARS-CoV-2, comorbid psychiatric and general medical illnesses, ARDS and ICU stay. Anosmia and hypogeusia are COVID-19-specific anxiety risk factors. Knowledge of the anxiety risk factors is essential to focus on timely interventions, because anxiety may be a complication of and exacerbate the COVID-19 course.An inverse correlation exists between resilience and anxiety because of COVID-19, and therefore efforts should be made to increase resilience in COVID-19 patients.In COVID-19, important anxiety mechanism is neuroinflammation resulting from activation of the immune system and an ensuing cytokine storm.The general approach to management of anxiety in COVID-19 should be compassionate, similar to that during trauma or disaster, with efforts focussed on instilling a sense of hope and resilience.In selecting pharmacological treatment of anxiety, the stress response and immune system effects should be key. Medications with cardio-respiratory adverse effects should be avoided in patients with respiratory problems.Anxiety is a disorder that will require for long-term follow up at least one month after COVID-19.

Neurocovid-19: A clinical neuroscience-based approach to reduce SARS-CoV-2 related mental health sequelae.

Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, is a disaster due to not only its psychosocial impact but it also to its direct effects on the brain. The latest evidence suggests it has neuroinvasive mechanisms, in addition to neurological manifestations, and as seen in past pandemics, long-term sequelae are expected. Specific and well-structured interventions are necessary, and that's why it's important to ensure a continuity between primary care, emergency medicine, and psychiatry. Evidence shows that 2003 SARS (Severe Acute Respiratory Syndrome) survivors developed persistent psychiatric comorbidities after the infection, in addition to Chronic Fatigue Syndrome. A proper stratification of patients according not only to psychosocial factors but also an inflammatory panel and SARS-Cov-2's direct effects on the central nervous system (CNS) and the immune system, may improve outcomes. The complexity of COVID-19's pathology and the impact on the brain requires appropriate screening that has to go beyond the psychosocial impact, taking into account how stress and neuroinflammation affects the brain. This is a call for a clinical multidisciplinary approach to treat and prevent Sars-Cov-2 mental health sequelae.

Importance of SARs-Cov-2 anosmia: From phenomenology to neurobiology

Anosmia and hypogeusia, the inability or decreased ability to smell and taste, have been reported as common complaints in SARS-CoV-2 patients who were still in an asymptomatic phase. These impairments affect the ability to sense odors in foods and the environment, obviously affecting quality of life, related to social interactions and general well-being. The British Association of Otorhinolaryngology (ENT-UK) considers loss of sense of smell in their list of COVID-19's markers of infection. Here we present two cases in which early manifestations of anosmia and hypogeusia were experienced with psycho-sensorial and atmospheric phenomena. Psychiatrists, neurologists and physicians in general should be aware of this symptom presentation in order to avoid mistreatment, given that persistent olfactory dysfunction might increase the risks of nutritional deficit and lead to development of adjustment disorders. All clinicians should be aware that the presentation of SARS-CoV-2's symptoms goes far beyond respiratory and sensorial dimensions and involves psychosensorial and neurological dimensions;these clinical observations could shed light on the neurobiological substrates involved in COVID-19 disease.