Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Immune response to SARS-CoV-2 in children: A review of the current knowledge

Host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID-19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. The deciphering of children's immune responses during COVID-19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID-19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS-CoV-2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS-CoV-2 infection and adaptive memory immunity is vital to prevent reinfection

SARS-CoV-2 variants and effectiveness of vaccines: a review of current evidence

The SARS-CoV-2 virus is rapidly evolving via mutagenesis, lengthening the pandemic, and threatening the public health. Until August 2021, 12 variants of SARS-CoV-2 named as variants of concern (VOC; Alpha to Delta) or variants of interest (VOI; Epsilon to Mu), with significant impact on transmissibility, morbidity, possible reinfection and mortality, have been identified. The VOC Delta (B.1.617.2) of Indian origin is now the dominant and the most contagious variant worldwide as it provokes a strong binding to the human ACE2 receptor, increases transmissibility and manifests considerable immune escape strategies after natural infection or vaccination. Although the development and administration of SARS-CoV-2 vaccines, based on different technologies (mRNA, adenovirus carrier, recombinant protein, etc.), are very promising for the control of the pandemic, their effectiveness and neutralizing activity against VOCs varies significantly. In this review, we describe the most significant circulating variants of SARS-CoV-2, and the known effectiveness of currently available vaccines against them

Association of clinical and epidemiological characteristics with COVID-19 BNT162b2 mRNA vaccine short-term adverse reactions in healthcare workers

Introduction The aim of the study was to investigate the prevalence and severity of adverse reactions (ARs) after immunization of healthcare workers (HCWs) with BNT162b2 vaccine and to associate them with clinical and epidemiological characteristics. Methods A form containing demographic and clinical data as well as ARs after both doses of the vaccine was completed, and statistical association analysis was performed. Results A total of 502 HCWs (females 78.3%) with mean age (±SD) 48.17 years (±12.97) participated. After the first dose, 404 (80.5%) HCWs reported at least one local AR (LAR) and 366 (72.9%) after the second dose (p-value=0.004). After the first dose, 121 (24.1%) HCWs reported at least one systemic AR (SAR) and 275 (54.8%) after the second dose (p-value<0.0001). In the logistic regression analysis, there was no association of gender or medical history of underlying disease with LARs. There was a negative association of age with the cumulative score (CS) of LARs (OR: 0.82, 95% CI: 0.69–0.96) after the first dose. Females had a positive association with CS of SARs following both doses (OR, 95% CI: 2.57, 1.39–4.73 and 2.71, 1.76–4.19, respectively). Age was negatively associated with CS of SARs (OR: 0.66, 95% CI: 0.57–0.76) after the second dose. Severe ARs included Bell’s palsy (1) and tinnitus with temporary hearing loss (1). Conclusion The administration of the BNT162b2 vaccine in our HCWs cohort had a good safety profile with the most common ARs being self-limited. An increasing rate of SARs following the second vaccine dose was noticed. Rare but severe possible ARs should be further investigated

Molecular Epidemiology of Enterovirus in Children with Central Nervous System Infections

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0&ndash;16 years) with suspected meningitis&ndash;encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray&reg; ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1&ndash;60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates

SARS-CoV-2 seroepidemiological study in healthcare workers and discordant results using seven different diagnostic methods

The aim of the study was to access the SARS-CoV-2 antibody seroprevalence in healthcare workers (HCWs) of a tertiary pediatric hospital after the first wave of the pandemic and to compare the results among seven commercially available antibody detection assays, including chemiluminescence (CMIA), electroluminescence (ECLIA), Epsilon nzyme-Linked Immunosorbent Assay (ELISA), and rapid immunochromatography (RIC). SARS-CoV-2 antibody detection was performed in serum samples of 1216 HCWs, using a reference CMIA assay and 8/1216 (0.66%) were detected positive. Positive serum samples were further tested with other assays; however, only one sample was positive by all tests. The rest 7 cases were negative with ECLIA and ELISA and gave discordant results with RIC test. Six months later, new serum samples of seropositive HCWs were analyzed with the same 7 tests, with inconsistent results again. Identification of reliable SARS-CoV-2 antibody tests is important to determine the actual number of past infections, the duration of antibodies, and guide public health decisions

Whole Exome Sequencing Points towards a Multi-Gene Synergistic Action in the Pathogenesis of Congenital Combined Pituitary Hormone Deficiency

Combined pituitary hormone deficiency (CPHD) is characterized by deficiency of growth hormone and at least one other pituitary hormone. Pathogenic variants in more than 30 genes expressed during the development of the head, hypothalamus, and/or pituitary have been identified so far to cause genetic forms of CPHD. However, the etiology of around 85% of the cases remains unknown. The aim of this study was to unveil the genetic etiology of CPHD due to congenital hypopituitarism employing whole exome sequencing (WES) in two newborn patients, initially tested and found to be negative for PROP1, LHX3, LHX4 and HESX1 pathogenic variants by Sanger sequencing and for copy number variations by MLPA. In this study, the application of WES in these CPHD newborns revealed the presence of three different heterozygous gene variants in each patient. Specifically in patient 1, the variants BMP4; p.Ala42Pro, GNRH1; p.Arg73Ter and SRA1; p.Gln32Glu, and in patient 2, the SOX9; p.Val95Ile, HS6ST1; p.Arg306Gln, and IL17RD; p.Pro566Ser were identified as candidate gene variants. These findings further support the hypothesis that CPHD constitutes an oligogenic rather than a monogenic disease and that there is a genetic overlap between CPHD and congenital hypogonadotropic hypogonadism

First Report of Diabetes Phenotype due to a Loss-of-Function ABCC8 Mutation Previously Known to Cause Congenital Hyperinsulinism

Monogenic Diabetes is relatively rare, representing only 1-2% of total diabetes cases; nevertheless, it is often misdiagnosed primarily as type 1 diabetes, leading to unnecessary insulin therapy and delayed recognition of affected family members. In the present article, we describe a case of a young, male patient who presented with hyperglycemia in the absence of ketosis and following genetic testing; he proved to harbor the loss-of-function p.Arg1353His (c.4058G>A) mutation in the ABCC8 gene, inherited from his mother. This mutation has been previously described in patients with Congenital Hyperinsulinism. Furthermore, different mutations in the ABCC8 gene have been linked with MODY 12, type 2, and gestational diabetes; however, to the best of our knowledge, this is the first report that associates this specific mutation with diabetes phenotype. ABCC8-related diabetes is characterized by remarkable heterogeneity in terms of clinical presentation and therapeutic approach. Early diagnosis and individualized treatment are essential to achieving metabolic targets and avoiding long-term diabetes complications

First Report of Diabetes Phenotype due to a Loss-of-Function ABCC8 Mutation Previously Known to Cause Congenital Hyperinsulinism.

Monogenic Diabetes is relatively rare, representing only 1-2% of total diabetes cases; nevertheless, it is often misdiagnosed primarily as type 1 diabetes, leading to unnecessary insulin therapy and delayed recognition of affected family members. In the present article, we describe a case of a young, male patient who presented with hyperglycemia in the absence of ketosis and following genetic testing; he proved to harbor the loss-of-function p.Arg1353His (c.4058G&gt;A) mutation in the ABCC8 gene, inherited from his mother. This mutation has been previously described in patients with Congenital Hyperinsulinism. Furthermore, different mutations in the ABCC8 gene have been linked with MODY 12, type 2, and gestational diabetes; however, to the best of our knowledge, this is the first report that associates this specific mutation with diabetes phenotype. ABCC8-related diabetes is characterized by remarkable heterogeneity in terms of clinical presentation and therapeutic approach. Early diagnosis and individualized treatment are essential to achieving metabolic targets and avoiding long-term diabetes complications

Ultra-Fast and Sensitive Screening for Antibodies against the SARS-CoV-2 S1 Spike Antigen with a Portable Bioelectric Biosensor

As a consequence of the progress of the global vaccination against the COVID-19 disease, fast, accurate and affordable assays are needed for monitoring the efficiency of developing immunity against the coronavirus at the population level. In this context, we herewith report the proof-of-concept development of an innovative bioelectric biosensor for the ultra-detection (in less than three minutes) of IgG antibodies against the SARS-CoV-2 S1 spike antigen. The biosensor comprises a disposable set of screen-printed electrodes upon which are immobilized cells engineered to bear the S1 protein on their surface. When anti-S1 antibodies are presented to the engineered cell population, a rapid, specific, and selective change of the cell membrane potential occurs; this is in turn recorded by a bespoke portable potentiometer. End results are communicated via Bluetooth to a smartphone equipped with a customized user interface. By using the novel biosensor, anti-S1 antibodies could be detected at concentrations as low as 5 ng/mL. In a preliminary clinical trial, positive results were derived from patients vaccinated or previously infected by the virus. Selectivity over other respiratory viruses was demonstrated by the lack of cross-reactivity to antibodies against rhinovirus. After further clinical validation and extension to also screen IgM, IgA and possible neutralizing antibodies, our approach is intended to facilitate the mass and reliable detection of antibodies in the early stages following vaccination and to monitor the duration and level of acquired immunity both in a clinical and self-testing environment