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.

Primary immune regulatory disorders (PIRD) are a group of diseases belong to inborn errors of immunity (IEI). They usually exhibit lymphoproliferation, autoimmunities, and malignancies, with less susceptibility to recurrent infections. Unlike to classical primary immune deficiencies, the autoimmune manifestations, such as cytopenias, enteropathy can be the first symptom of diseases, and they are typically resistant to treatment. Increasing awareness for PIRD among specialists and multidisciplinary team approach would provide early diagnosis and treatment that can prevent end-organ damages related with the diseases. In recent years, many PIRD diseases have been described and understanding the immunological pathways linked to the disorders provides us an opportunity to use directed therapies for specific molecules, which usually offer better disease control than known classical immunosuppressants. In this review, in the light of last literature researches, we will discuss the common PIRD diseases and explain their clinical symptoms and recent treatment modalities.

Background: Childhood asthma is clinically heterogeneous, yet simple clinical approaches for describing concurrent disease burden are limited. We tested whether a two-axis phenotype matrix—built from early-onset and/or high-burden wheeze and atopic load—is associated cross-sectionally with treatment-defined severity and control in school-aged children with asthma. This exploratory, unvalidated classification requires prospective external validation before clinical use. Methods: In a two-center retrospective cross-sectional study, 337 children aged 6–12 years with physician-confirmed asthma were classified into four clinical strata (low-burden, familial/atopic-dominant, wheeze-dominant, atopic-wheezing). The primary outcome was moderate-to-severe asthma, defined by controller treatment step and deliberately independent of acute events. Variables independently associated with the outcomes were identified using multivariable logistic regression with prespecified sensitivity analyses; trends across ordered wheezing-onset categories were assessed using the Cochran–Armitage trend test, adjusted associations were confirmed by likelihood-ratio tests, and secondary outcomes were false-discovery-rate corrected. Results: The atopic-wheezing stratum was the largest group (140/337, 41.5%) and carried the highest burden: moderate-to-severe asthma 49.3% vs. 17.4% in low-burden and uncontrolled asthma 42.1% vs. 13.0% (both q < 0.01). Adverse outcomes were generally more frequent with earlier wheezing onset (moderate-to-severe asthma 26.9% to 57.9% from no early wheeze to onset ≤ 12 months; p for trend <0.001). After adjustment, the atopic-wheezing stratum had the largest adjusted odds ratios for both moderate-to-severe asthma (aOR 4.49, 95% CI 1.91–10.54) and uncontrolled asthma (aOR 4.78, 95% CI 1.85–12.35), and remained significant across all sensitivity analyses. Passive smoke exposure was independently associated with uncontrolled asthma (aOR 1.86, 95% CI 1.13–3.05) but not severity. The FEV1/FVC z-score differed significantly across strata and was lowest in the atopic-wheezing group (median z-score −1.28 vs. +0.10 in low-burden; p < 0.001). Conclusions: The co-occurrence of high atopic load with early-onset or high-burden wheezing defined the clinical stratum with the highest observed treatment requirement and poorest control, using only routine history and standard allergy work-up. Passive smoke exposure was independently associated with uncontrolled asthma.