To the Editor, Many authors recently reported the effect of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on patients affected by Inborn Errors of Immunity (IEI). 1,2 Although mostly experiencing a mild disease and the course of the infection is comparable or even less symptomatic than the general population, young male IEIs patients were more severely affected and more frequently admitted to intensive care unit compared with the age-matched healthy peers. 3 Most viral variants were actually first described in immunocompromised patients. 4,5 Indeed, impaired B and/or T cell function can be responsible for persisting viral shedding often observed in IEI patients with subsequent higher risk of persistent viral replication and mutation within the host. 6 Noteworthily, in the last 2 years Inborn Errors of type I IFN immunity and autoantibodymediated phenocopies of IEIs were identified as responsible for life-threatening COVID-19. These conditions were not considered in the studies about IEIs and SARS-CoV-2 infection. 7,8 Predisposition to increased risk and most severe infection in IEI, despite a lack of clear data in favor of a high risk for progression to severe COVID-19, led the scientific community to recommend the use of early SARS-CoV2-directed treatments to potentially reduce the incidence of long-lasting infection, as well as morbidity and mortality risk. 9Casirivimab-imdevimab, also known as REGEN-COV, is an antispike mAb that has been authorized for the treatment of high-risk patients (>12 years of age, >40 kg) with mild-to-moderate COVID-19. 10 Bamlanivimab, named LY-CoV555, then combined with etesevimab, showed a beneficial effect for accelerating the natural decline of the viral load over time. In December 2021, it was approved by FDA for patients<12 years. 10 Sotrovimab, formerly known as VIR-7831, is an engineered human mAb that neutralizes SARS-CoV-2. 10 There are several data confirming the safety and efficacy in both adults and pediatric population. 11 We describe a cohort of 63 SARS-CoV-2-infected IEI patients, providing the first case series report on the early employment of anti-SARS-CoV-2 treatments with antiviral drugs and MAbs in these patients (Table S1). Thirty-nine patients were younger than 18 years (median age 9.5 years), whereas 24 were adults (median age 33 years). Male-to-female ratio was 1:1. Seven individuals have been

Background Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune‐mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was established in particular in the combined and chronic forms. Objective Aim of this study is to provide clinical‐immunological parameters to hematologists useful for a prompt identification of children with immune cytopenias deserving a deeper immunological and genetic evaluation. Methods We retrospectively collected 47 pediatric patients with at least one hematological disorder among which persistent/chronic ITP, AIHA, and AIN, aged 0–18 years at onset of immune cytopenias and/or immune‐dysregulation. The cohort was divided into two groups (IEI+ and IEI−), based on the presence/absence of underlying IEI diagnosis. IEI+ group, formed by 19/47 individuals, included: common variable immune deficiency (CVID; 9/19), autoimmune lymphoproliferative syndrome (ALPS; 4/19), DiGeorge syndrome (1/19), and unclassified IEI (5/19). Results IEI prevalence among patients with ITP, AIHA, AIN, and Evans Syndrome was respectively of 42%, 64%, 36%, and 62%. In IEI+ group the extended immunophenotyping identified the presence of statistically significant (p < .05) specific characteristics, namely T/B lymphopenia, decrease in naїve T‐cells%, switched memory B‐cells%, plasmablasts%, and/or immunoglobulins, increase in effector/central memory T‐cells% and CD21low B‐cells%. Except for DiGeorge and three ALPS patients, only 2/9 CVID patients had a molecular diagnosis for IEI: one carrying the pathogenic variant CR2:c.826delT, the likely pathogenic variant PRF1:c.272C> and the compound heterozygous TNFRSF13B variants p.Ser144Ter (pathogenic) and p.Cys193Arg (variant of uncertain significance), the other one carrying the likely pathogenic monoallelic variant TNFRSF13B:p.Ile87Asn. Conclusion The synergy between hematologists and immunologists can improve and fasten diagnosis and management of patients with immune cytopenias through a wide focused clinical/immunophenotypical characterization, which identifies children worthy of IEI‐related molecular analysis, favouring a genetic IEI diagnosis and potentially unveiling new targeted‐gene variants responsible for IEI phenotype.

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Sickle cell disease (SCD) is a condition of functional hypo-/a-splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune-dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform an in-depth immunophenotypical characterization of SCD pediatric patients, looking for plausible correlations between immunological biomarkers, the impact of hydroxyurea (HU) treatment and clinical course. This was an observational case–control study including 43 patients. The cohort was divided into two main groups, SCD subjects (19/43) and controls (24/43), differing in the presence/absence of an SCD diagnosis. The SCD group was split up into HU+ (12/19) and HU− (7/19) subgroups, respectively receiving or not a concomitant HU treatment. The principal outcomes measured were differences in the immunophenotyping between SCD patients and controls through chi-squared tests, t-tests, and Pearson’s correlation analysis between clinical and immunological parameters. Leukocyte and neutrophil increase, T-cell depletion with prevalence of memory T-cell compartment, NK and B-naïve subset elevation with memory and CD21low B subset reduction, and IgG expansion, significantly distinguished the SCD HU− subgroup from controls, with naïve T cells, switched-memory B cells and IgG maintaining differences between the SCD HU+ group and controls (p-value of <0.05). The mean CD4+ central-memory T-cell% count was the single independent variable showing a positive correlation with vaso-occlusive crisis score in the SCD group (Pearson’s R = 0.039). We report preliminary data assessing plausible clinical implications of baseline and HU-related SCD immunophenotypical alterations, which need to be validated in larger samples, but potentially affecting hypo-/a-splenism immuno-chemoprophylactic recommendations.

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