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Current understanding of how immunodeficiencies impact protective responses against viral infections and vaccination is primarily derived from adult cohorts that may not accurately reflect the pediatric, adolescent, and young adult population. This cross-sectional study aimed to evaluate immune responses in this underrepresented population affected by various immunodeficiencies after SARS-CoV-2 infection, two doses of the mRNA BNT162b2 vaccine, or after a combination of both. We analyzed blood samples from 102 immunocompromised patients (IC) (5–25 years) categorized into groups of primary immunodeficiencies (PID, n=17), bronchial asthma and allergic rhinitis (BA-AR, n=39), rheumatoid diseases (RD, n=21), and individuals who had undergone hematopoietic stem cell transplantation (HSCT, n=28), as well as 30 healthy individuals (9–26 years). We measured titres of Spike-specific IgM, IgA, and IgG antibody classes (including IgG subclasses) in plasma using ELISA and evaluated their inhibitory potential in a Spike-ACE2 cell-based internalization assay. Spike-specific CD4 T-cells were examined using a flow cytometry-based proliferation assay (FASCIA). In the IC group, all participants except eight generated detectable levels of IgG antibodies. The IgG titres induced by vaccination (Geometric mean titre (GMT vac ) = 205023, 95% CI: 116074-362136) and a combination of vaccination and infection (GMT hyb = 172819, 95% CI: 33133-901403) were higher than after infection (GMT inf = 3323, 95% CI: 578-19109, P vac/inf = .006 and P hyb/inf = .001). On the other hand, the hybrid immunity induced the highest IgA titres (GMT hyb = 2672, 95% CI: 566-12623) compared to vaccination (GMP vac = 275, 95% CI: 97-777, P hyb/vac = .016) and infection (GMT inf = 60, 95% CI: 13-280, P hyb/inf = .002). The IgG titres in vaccinated and hybrid immunity groups strongly correlated (r Spearman = 0.86, P <.0001) with the levels of antibodies inhibiting the internalization of Spike protein (S protein) in a cell-based assay. Most IC patients (except five) also developed above-threshold Spike-specific CD4 T-cell responses, which were not statistically different from the responses in the healthy control group. Our data show that infection and vaccination can induce protective humoral or cellular responses against SARS-CoV-2 in IC patients. The activated cellular response in patients with agammaglobulinemia may assist them in overcoming viral infections.

Recently emerged SARS-CoV-2 variants show resistance to some antibodies that were authorized for emergency use. We employed hybridoma technology combined with authentic virus assays to develop second-generation antibodies, which were specifically selected for their ability to neutralize new variants of SARS-CoV-2. AX290 and AX677, two monoclonal antibodies with non-overlapping epitopes, exhibit subnanomolar or nanomolar affinities to the receptor binding domain of the viral Spike protein carrying amino acid substitutions N501Y, N439K, E484K, K417N, and a combination N501Y/E484K/K417N found in the circulating virus variants. The antibodies showed excellent neutralization of an authentic SARS-CoV-2 virus representing strains circulating in Europe in spring 2020 and also the variants of concern B.1.1.7 and B.1.351. Finally, the combination of the two antibodies prevented the appearance of escape mutations of the authentic SARS-CoV-2 virus. The neutralizing properties were fully reproduced in chimeric mouse-human versions, which may represent a promising tool for COVID-19 therapy.

Introduction Despite the continuously growing number of therapeutic options for type 2 diabetes mellitus (T2DM) including insulins, a large percentage of patients fail to achieve HbA1c targets. Several real-world studies focused on patients with T2DM receiving insulin treatment in outpatient settings were conducted, but information about real-world in-hospital insulin management is lacking. The aim of this study was to describe the management of insulin therapy with a focus on basal-bolus and premixed insulin regimens in patients with T2DM under routine in-hospital medical practice in the Czech Republic. Methods This non-interventional prospective study was conducted from June 2014 to December 2017 in 22 centers in the Czech Republic under routine clinical practice conditions. Adult patients admitted to hospital with metabolically uncontrolled T2DM [HbA1c ≥ 60 mmol/mol; > 7.6% Diabetes Control and Complications Trial (DCCT)] and there treated with basal-bolus and premixed insulin regimens were documented during hospitalization. Results Overall, 369 patients with T2DM (54.7% male, mean age 64.44 ± 13.84 years, BMI 31.10 ± 6.00 kg/m 2 , duration of diabetes 8.11 ± 9.93 years, HbA1c 95.90 ± 24.38 mmol/mol, length of stay was 7.94 ± 4.53 days) were included. The percentage of glucose values under 10 mmol/l at time of randomization (the group with basal-bolus insulin regimen vs. the premix insulin regimen group) was 24.2% vs. 33.5% ( p  = 0.053), at time of first insulin dose adjustment it was 43.1% vs. 50.0% ( p  = 0.330), and 1 day before hospital discharge it was 61.7% vs. 61.4% ( p  = 0.107). A hypoglycemic event occurred in a total of 15 patients in the basal-bolus regimen group, and no hypoglycemic event occurred in the premixed insulin regimen group. Conclusion In-hospital insulin management regarding basal-bolus and premixed insulin regimens is safe and in concordance with current international recommendations.

Spindle cell hemangioma is a benign vascular tumor typically occurring in the dermis or subcutis of distal extremities as red–brown lesions that can grow in both size and number over time. They can be very painful and potentially disabling. A family history of cancer or previous history may be relevant and must be taken into consideration. Juxtaglomerular cell tumor (reninoma) is an extremely rare cause of secondary hypertension diagnosed mostly among adolescents and young adults. Excessive renin secretion results in secondary hyperaldosteronism. Subsequent hypokalemia and metabolic alkalosis, together with high blood pressure, are clues for clinical diagnosis. Histological examination of the excised tumor leads to a definitive diagnosis. Reninoma is found in subcapsular localization, in most cases as a solitary mass, in imaging studies of kidneys. Exceptionally, it can be located in another part of a kidney. Both spindle cell hemangioma and reninoma are extremely rare tumors in children and adolescents. Herein, the authors present a case report of a patient with hereditary BRCA1 interacting protein C-terminal helicase 1 (BRIP1) mutation, spindle cell hemangioma, and secondary hypertension caused by atypically localized reninoma.