COVID-19 Vaccination in Patients with Inborn Errors of Immunity Reduces Hospitalization and Critical Care Needs Related to COVID-19: a USIDNET Report.

BACKGROUND: The CDC and ACIP recommend COVID-19 vaccination for patients with inborn errors of immunity (IEI). Not much is known about vaccine safety in IEI, and whether vaccination attenuates infection severity in IEI. OBJECTIVE: To estimate COVID-19 vaccination safety and examine effect on outcomes in patients with IEI. METHODS: We built a secure registry database in conjunction with the US Immunodeficiency Network to examine vaccination frequency and indicators of safety and effectiveness in IEI patients. The registry opened on January 1, 2022, and closed on August 19, 2022. RESULTS: Physicians entered data on 1245 patients from 24 countries. The most common diagnoses were antibody deficiencies (63.7%). At least one COVID-19 vaccine was administered to 806 patients (64.7%), and 216 patients received vaccination prior to the development of COVID-19. The most common vaccines administered were mRNA-based (84.0%). Seventeen patients were reported to seek outpatient clinic or emergency room care for a vaccine-related complication, and one patient was hospitalized for symptomatic anemia. Eight hundred twenty-three patients (66.1%) experienced COVID-19 infection. Of these, 156 patients required hospitalization (19.0%), 47 required ICU care (5.7%), and 28 died (3.4%). Rates of hospitalization (9.3% versus 24.4%, p < 0.001), ICU admission (2.8% versus 7.6%, p = 0.013), and death (2.3% versus 4.3%, p = 0.202) in patients who had COVID-19 were lower in patients who received vaccination prior to infection. In adjusted logistic regression analysis, not having at least one COVID-19 vaccine significantly increased the odds of hospitalization and ICU admission. CONCLUSION: Vaccination for COVID-19 in the IEI population appears safe and attenuates COVID-19 severity.

Management of Atopy with Dupilumab and Omalizumab in CADINS Disease.

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

Implementation of an evidence-based trauma-focused treatment for traumatised children and their families during the war in Ukraine: a project description.

The full-scale invasion of Ukraine by Russia in February 2022 led to an increase of traumatic events and mental health burden in the Ukrainian general population. The (ongoing) traumatisation can have a crucial impact on children and adolescents as they are especially vulnerable for developing trauma-related disorders such as Post Traumatic Stress Disorder (PTSD) or Depression. To date, these children have only very limited access to trauma-focused evidence-based treatments (EBTs) by trained mental health specialists in Ukraine. The fast and effective implementation of these treatments in Ukraine is crucial to improve the psychological wellbeing of this vulnerable population. This letter to the editor describes an ongoing project which implements a trauma-focused EBT called 'Trauma-Focused Cognitive Behavioural Therapy' (TF-CBT) in Ukraine during the war. In collaboration with Ukrainian and international agencies, the project 'TF-CBT Ukraine' was developed and implemented starting in March 2022. The project entails a large training programme for Ukrainian mental health specialists and the implementation of TF-CBT with children and their families in and from Ukraine. All components of the project are scientifically evaluated on a patient and therapist level, cross-sectionally and longitudinally, in a mixed-methods design. All together nine training cohorts with N = 133 Ukrainian therapists started the programme, all monthly case consultations (15 groups) and treatments of patients are still ongoing. Lessons learnt from this first large-scale implementation project on an EBT for children and adolescents impacted by trauma in Ukraine will help inform the field on challenges and also possibilities to expand such efforts. On a broader level, this project could be one small step in the process of helping children overcome the negative effects and experience resilience in the context of a war-torn nation.

Lymphoma in Partial DiGeorge Syndrome: Report of 2 Cases.

Primary immunodeficiency diseases are associated with an increased tendency for noninfectious complications of autoimmunity and malignancy, particularly leukemia and lymphoma. The mechanisms of immune dysregulation have been linked to the combination of dysregulated immune cells and environmental factors such as infections. In particular, dysfunction in T-cell subsets and Epstein-Barr virus contributes to the development of autoimmunity and lymphoproliferative disease in primary immunodeficiency diseases. There are scant reports of patients with partial DiGeorge syndrome and Epstein-Barr virus-driven lymphoma. We report 1 patients with partial DiGeorge syndrome who developed lymphoma, and review reported cases in the literature.

Atopy: A Collection of Comorbid Conditions.

The concept of atopy was initially developed in the first quarter of the 20th century on the basis of clinical observations without any knowledge of pathogenic mechanisms. Atopy involves a collection of comorbidities that share pathogenic features, and atopic comorbidities affect outcomes of concomitant conditions rather than existing synchronously. The clinical importance of understanding the relationship of these conditions is necessary because the treatment of one condition influences the others, and the development of one leads to or precedes the development of another. Environmental influences and multigenetic predispositions result in complex relationships among the atopic conditions sharing a type 2 pathogenesis. The specialty of Allergy and Immunology is devoted to managing the comorbidities of atopy, and better understanding of their connections can improve patient care.

An intensive form of trauma focused cognitive behaviour therapy in an acute adolescent inpatient unit: An uncontrolled open trial.

PURPOSE: Post-traumatic stress disorder (PTSD) rates among hospitalised adolescents are between 21% and 32%, and there is a lack of evidence-based interventions for this population. Trauma-focused cognitive behaviour therapy (TF-CBT) is an evidence-based intervention for children and adolescents with PTSD; however, it has not been implemented in an acute adolescent inpatient unit. This study examines the implementation of an intensive form of TF-CBT in an adolescent inpatient unit. METHOD: An uncontrolled open trail study was conducted where 15 adolescents diagnosed with PTSD were treated with an intensive form of TF-CBT. Measures used were the University of California, Los Angeles' (UCLA) PTSD Reaction Index for Diagnostic and Statistical Manual of Mental Disorders (4th ed., Adolescent Version; DSM-IV-Adolescent Version), the National Stressful Events Survey PTSD Short Scale (NSESSS) and the Children's Global Assessment Scale (CGAS). RESULTS: Adolescents received an average of nine sessions of TF-CBT over a period of 28 days. The average NSESSS on admission was 23.73 and 8.27 at discharge; the CGAS average on admission was 19 and on discharge was 48.7; both were statistically significant changes. CONCLUSION: Preliminary findings support the use of an intensive form of TF-CBT to treat adolescents with PTSD admitted to acute adolescent inpatient units indicating the need for further research in this area.