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.

Transplant-acquired allergy (TAA) was firstly described as transplant-acquired food allergy (TAFA) after bone marrow transplantations and mostly observed in a transient form. The picture is complicated by numerous case reports of TAFA after the receipt of liver grafts from donors with no documented history of food allergy. The estimated prevalence of TAFA among young children in the literature has been documented in various studies ranging from 6% to 57%. Although TAA is mostly found to be associated with liver transplantation; it has been recently reported to be related with heart, intestinal, lung and even renal transplantations in adults. Previous reviews of published cases of liver TAA misleadingly emphasized the predominance of children and the absence of TAA in cardiac, pulmonary, and renal transplant recipients. In different studies, the male/female ratio is equal. Literature data suggest that children with TAFA typically present within the first year after surgery and are typically allergic to multiple foods. The pathogenesis of TAA is not still completely understood. Most of the studies support the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is one of the main contributors to TAA in these patients. In the light of recent findings, other possible mechanisms can be summarized as following: (1) the recovery of delayed type hypersensitivity; (2) late manifestation of food allergy; (3) intestinal injury as well as inhibition of cellular energy production by tacrolimus; and (4) transfer of food-specific IgE or lymphocytes. Thus, interplay between hematopoietic cells from the transplanted organ and recipient specific factors (e.g., younger age and atopic background) seem to underlie the development of TAA. Most patients will have symptomatic improvement following reduced immunosuppression and an appropriately restricted diet. Nevertheless, some studies suggest that atopic diseases occur in some of pediatric liver transplant recipients, with manifestations including food allergy, eczema, allergic rhinitis, and asthma. More studies would be needed including greater number of patients to determine whether TAA is transient or not in pediatric/adult solid organ recipients.

Development of the child's immune system tends to be directed toward a T-helper 2 (Th2) phenotype in infants. To prevent development of childhood allergic/atopic diseases, immature Th2-dominant neonatal responses must undergo environment-driven maturation via microbial contact in the early postnatal period. Lactic acid bacteria and bifidobacteria are found more commonly in the composition of the intestinal flora of nonallergic children. Epidemiological data also showed that atopic children have a different intestinal flora from healthy children. Probiotics are ingested live health-promoting microbes that can modify intestinal microbial populations in a way that benefits the host; and enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against atopy. There is insufficient but very promising evidence to recommend the addition of probiotics to foods for prevention and treatment of allergic diseases, especially atopic dermatitis. Clinical improvement especially in allergic rhinitis and IgE-sensitized (atopic) eczema has been reported too. Literature data for food allergy/hypersensitivity and asthma are not adequate for this guaranteed conclusion; however, clinical benefit of probiotic therapy depends on numerous factors, such as type of bacterium, dosing regimen, delivery method, and other underlying host factors, e.g., the age and diet of the host. The selection of the most beneficial probiotic strain, the dose, and the timing of supplementation still need to be determined. Accordingly, probiotics can not be recommended generally for primary prevention of atopic disease; and if probiotics are used in atopic infants/children for any reason, such as therapy or prevention, cautionary approach ought to be taken.

Mast cells are a subtype of white blood cells and are involved in the immune system. These cells contain many chemical substances called mediators, which are involved in the allergic response. The fact that mast cells play a role in many events that require urgent intervention, especially anaphylaxis, has led to a more detailed study of these cells. The diseases also caused by dysfunctions of mast cells have been examined in many circumstances. For instance, mast cell activation syndrome is known as an augmented number of cells due to decreased cell death, resulting in clinical symptoms affecting many systems. The main common symptoms include flushing, hypotension, urticaria, angioedema, headache, vomiting and diarrhea. Although the underlying mechanism is not yet clearly known, we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.