Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test ( n = 25) and/or a lung tomography scoring (CORADS) ≥4 ( n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p < .001). Concerning predictive roles of laboratory markers at admission, deceased subjects compared to survived had significantly higher CRP, procalcitonin, Troponin‐T, ferritin, and total‐lung‐score ( p = .020, p = .003, p = .014, p = .013, p = .020; respectively), and lower absolute lymphocyte count, albumin, and trough IgG ( p = .012, p = .022, p = .011; respectively). Conclusion Our data disclose a highly vulnerable IEI subgroup particularly disadvantaged for COVID‐19 despite their youth. Future studies should address this vulnerability and consider giving priority to these subjects in SARS‐Cov‐2 therapy trials.

Introduction The COVID‐19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim To understand how CU patients are affected by the COVID‐19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID‐19. Materials and Methods Our cross‐sectional, international, questionnaire‐based, multicenter UCARE COVID‐CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results The COVID‐19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID‐19 patient care, which negatively impacted on the care of urticaria patients. The rate of face‐to‐face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19. Conclusions The COVID‐19 pandemic brings major changes and challenges for CU patients and their physicians. The long‐term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.

Background Lockdown was imposed for children for 75 days in Turkey to limit the spread of COVID‐19. During this period, children have to stay indoors, which might probably increase their exposures to indoor allergens and pollutants. Besides, reduced exposures to respiratory tract infections and outdoor pollutants might be favorable outcomes of this lockdown period. We evaluated the effects of the lockdown on house dust mite (HDM)–sensitized children with respiratory allergies. Methods Three‐month clinical and medication data of 165 mild‐moderate asthmatic children with or without allergic rhinitis (AR), who were grouped according to their HDM sensitization status, were retrieved from patient records. Demographics, asthma control tests, nasal visual analog scores, and outdoor air quality monitoring data were used for assessments in comparisons with the same period in the previous year. Results Eighty‐four patients had asthma, and 81 patients had asthma with AR. Sensitization to HDM was present in 61.8% of the children. Patients experienced reduced numbers of upper respiratory tract infections (P = .008) and reduced asthma exacerbations (P < .001) compared with the same period in the previous year. Asthma control tests were significantly improved (P < .001), and cumulative inhaled corticosteroid usages were significantly reduced (P < .001). Noteworthily, nasal symptoms were significantly worsened in HDM‐sensitized asthmatics with AR (P < .001). Conclusions This study highlighted that reduction in respiratory tract infections and outdoor pollution may play roles in asthma control and prevent exacerbations despite continuous indoor allergen exposure. Besides, worsening of nasal symptoms in HDM‐sensitized asthmatics with AR implies the importance of indoor avoidance measures for AR control.

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next‐generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon‐based targeted NGS panel, which contained 18 most common SCID‐related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease‐causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom‐made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK− SCID). Incidence of autosomal‐recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom‐made sequencing panel was able to identify and confirm the previously known and novel disease‐causing variants with high accuracy.

The capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is an autosomal recessive inborn error of immunity (IEI) leading to combined T-cell, B-cell, and NK cell defects. 1,2 CARMIL2, also known as RGD motif, leucine-rich repeats, tropomodulin domain, and proline-rich containing protein (RLTPR), is a member of the CARMIL family. This family consists of three paralogous genes (CARMIL1, CARMIL2, and CARMIL3), producing multidomain proteins with high sequence homology. They contain an N-terminal pleckstrin homology (PH) domain, a leucine-rich repeat (LRR) domain, a homodimerization domain (HD), and a C-terminal domain including a capping protein binding region (CBR) and a proline-rich region (PRR).While all CARMILs have a capacity to bind to the capping proteins and regulate actin assembly, each protein also has a unique cellular function. 3 CARMIL1 activates the Trio-Rac1 pathway to enhance Arp2/3-mediated actin polymerization, 4,5 whereas CARMIL2 binds to cellular membranes via vimentin, and activates T cells by ligating CD28 and CARMA1 to mediate NFk B signaling. 6,7 Mice expressing mutated Carmil2 gene are not able to conduct CD28-mediated activation of its effector protein kinase C theta (PKCθ), abrogating effector memory CD4 + T and regulatory T cells (Treg) development. 7,8 CARMIL2 is also necessary for invadopodia formation, cell polarity, lamellipodial assembly, membrane ruffling, macropinocytosis, and cell migration. 3 The CARMIL3 is expressed mainly in the brain and spinal cord, and identified as oncofetal gene; however, recently, it was demonstrated as essential regulator of the proinflammatory cytokines in macrophages. 3,9 The human CARMIL2 gene was originally identified by Matsuzaka et al. and shown to be downregulated in affected skin cells of psoriasis vulgaris patients. 10 The CARMIL2 protein is expressed in the cytoplasm, especially in the skin, lymphoid tissue, and gastrointestinal system, and was demonstrated to play a role in wound healing. 3 So far, fewer than 40 cases of CARMIL2 deficiency have been reported worldwide. Patients with CARMIL2 deficiency present with a broad range of symptoms, including cutaneous and respiratory allergies mainly characterized by eczematous lesions, early-onset