Stress hyperglycemia, Diabetes mellitus and COVID-19 infection: The impact on newly diagnosed type 1 diabetes.

Several recent studies have documented an increased incidence of newly diagnosed type 1 Diabetes (T1D) cases in children and adolescents during the COVID-19 pandemic and a more severe presentation at diabetes onset. In this descriptive study, we present the experience of the Diabetes Centre of the Division of Endocrinology, Diabetes, and Metabolism of the First Department of Pediatrics of the National and Kapodistrian University of Athens Medical School at "Aghia Sophia" Children's Hospital in Athens, Greece, concerning new cases of T1D diagnosis during the COVID-19 pandemic (March 2020- December 2021). Patients who had already been diagnosed with T1D and needed hospitalization due to poor control during the pandemic have been excluded from this study. Eighty- three children and adolescents with a mean age of 8,5 ± 4.02 years were admitted to the hospital due to newly diagnosed T1D during this 22 months' period in comparison to 34 new cases in the previous year. All patients admitted during the pandemic with a new diagnosis of T1D, presented in their majority with DKA (Ph: 7.2) representing an increase of new severe cases in comparison to previous years (Ph 7.2 versus 7.3, p value: 0.021, in the previous year), [p-value: 0.027]. 49 cases presented with DKA, of which 24 were characterized moderate and 14 severe DKA (28.9% and 16,9%, respectively), while 5 patients newly diagnosed, needed to be admitted to the ICU to recover from severe acidosis. Whether a previous COVID- 19 infection could have been the triggering factor is not supported by the SARS-Cov2 specific antibodies analysis in our cohort of patients. As far as HbA1c is concerned there was no statistically significant difference between the pre COVID-19 year and the years of the pandemic (11.6% versus 11.9%, p- value: 0.461). Triglycerides values were significantly higher in patients with new onset T1D during COVID-19 years compared to those before the pandemic (p value= 0.032). Additionally, there is a statistically significant correlation between Ph and Triglycerides for the whole period 2020-2021 (p-value<0.001), while this correlation is not significant for the year 2019. More large- scale studies are required to confirm these observations.

COVID-19 in patients with pulmonary alveolar proteinosis: a European multicentre study.

Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.

SARS-CoV-2 seroepidemiology in paediatric population during Delta and Omicron predominance.

Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0-16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24-144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-value<0.0001). Seropositivity increased for all age groups, except for the age group of 0-1 year (P-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12-16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12-16 years [32.2 COI (7-77.1) vs. 11.4 COI(2.8-50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.

NFB-15. "Cognitive Impairments in Children and Adolescents with Neurofibromatosis"

INTRODUCTION-BACKGROUND: Cognitive, learning and/or behavioral disorders are common (up to 70%) complications of neurofibromatosis (NF). The first multidisciplinary-clinic for neurocutaneous-disorders was established at the Aghia Sophia Children’s Hospital in Athens, Greece, in 2016. Since then, more than 200 children and adolescents with NF have been examined. SCOPE: Acknowledging and indicating awareness on the devastating life-long consequences (poor academic performance, behavioral problems, and limited career prospectives) that can result from cognitive impairment, a research collaboration with educational specialists was recently implemented to examine the neurocognitive functions of children and adolescents with NF. MATERIALS: Children and adolescents aged 7-14 years who suffer from NF type I or type II, were eligible for study entry. The third edition of the Wechsler Intelligence Scale (WISC-III) was used to measure participants’ cognitive function. RESULTS: Preliminary results of this ongoing study are presented. Patients’ recruitment was limited by the coronavirus disease 2019 (COVID-19) restrictions. At this stage, the research involved 10 participants suffering from NF, with mean (± SD) age of 11.55 (± 1.80) years and a male-to-female ratio of 1. The mean (± SD) full-scale intelligence quotient (IQ) was 85.50 (± 18.80), corresponding to the 0.3rd to 73th percentile range. The mean (± SD) scores of performance IQ and verbal IQ were 84.90 (± 17.43) and 89.40 (± 17.23) respectively, corresponding to the 1st to 73rd percentile range for both subscales. CONCLUSION: Significant cognitive deficits, according to the percentile scores of WISC-III, were demonstrated in the small number of children and adolescents suffering from NF (type I or type II). Cognitive assessment, as part of the multidisciplinary approach of these patients is warranted, to aid timely educational interventions and improve patient learning outcomes.

COVID-19 in patients with Pulmonary Alveolar Proteinosis A European multicenter study

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) signaling is essential in both alveolar macrophages (AMs) differentiation and activation of lung immune cells [1]. Differentiated AMs are crucial in both the elimination of alveolar microbes and surfactant clearance. The disruption of the GM-CSF axis in alveolar macrophages leads to the development of pulmonary alveolar proteinosis (PAP) [1]. In the majority of patients this relates to the presence of autoantibodies against GM-CSF autoimmune (a)PAP but there are multiple other causes [1, 2, 3]. GM-CSF deficient animals may have impaired lung inflammatory response to commensal microbes and humans with PAP may occasionally develop opportunistic lung infections [4]. The mainstay of pharmacological treatment in aPAP is inhaled GM-CSF which is off-label but increasingly used worldwide [5, 6, 7, 8, 9].

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.

Perceived Changes in Emotions, Worries and Everyday Behaviors in Children and Adolescents Aged 5-18 Years with Type 1 Diabetes during the COVID-19 Pandemic.

The COVID-19 pandemic and the consequent restrictive measures may be related to increased stress and anxiety and to changes in daily behaviors. Children with type 1 diabetes (T1D) are a vulnerable group due to their difficulties in achieving glycemic control and to their medical and psychological comorbidities. The purpose of the current study was to the investigate the changes on emotional and behavioral parameters in children with T1D due to the Coronavirus crisis. A total of 152 children and adolescents, aged 5-18, were studied: 114 (62 boys) with T1D and 38 (19 boys) healthy volunteers (HV) (controls). The study was performed at the Diabetes Center, Aghia Sofia Children's Hospital, during the first national lockdown in Greece. The CRISIS questionnaire was completed by parents/caregivers. The data were collected in May 2020 and referred to two time-points: three months prior (before the pandemic), and the past two weeks. During the lockdown, it was observed significant aggravation in the "Emotion/Worries (EW)" symptoms in both groups (logEW-before vs. logEW-during the crisis, T1D: 2.66 ± 0.23 vs. 3.00 ± 0.21, p < 0.001 and HV: 2.62 ± 0.16 vs. 2.83 ± 0.18, p < 0.001). Deterioration of "ΕW" was recorded for 93.0% of those with T1D and 92.1% of the HV. "EW" during the lockdown were affected by: previous psychological condition, COVID-related concerns, and "Life Changes due to the COVID-19 crisis in the past two weeks (LC)". Deterioration was observed in the "daily behaviors" and "use of digital media" for all of the children. The crisis and the associated restrictions negatively affected both the lifestyle parameters and the behavioral and emotional variables of the children with T1D.

Coagulation Abnormalities and Management in Hospitalized Pediatric Patients With COVID-19.

BACKGROUND: The incidence and severity of coagulation abnormalities have not been extensively studied in pediatric populations with coronavirus disease 2019 (COVID-19). Moreover, their association with an increased risk for thromboembolic events remains unclear, and there is a lack of evidence for optimal prophylactic antithrombotic management. The aim of our study was to present our experience in evaluation, management, and long-term outcomes of coagulation abnormalities in pediatric hospitalized patients with COVID-19. METHODS: A prospective study was performed in all children hospitalized for COVID-19 during a 6-month period focusing on patients' coagulation abnormalities, the normalization of the coagulation profile with or without anticoagulation prophylaxis and the clinical outcome of the disease. RESULTS: Two hundred twenty-three patients (median age: 11.4 months) were enrolled in the study. Coagulation abnormalities were detected in 92.4% of patients with increased D-dimer levels to be the most common abnormality detected in 84.3% of patients. Prophylactic anticoagulation was initiated only in 7 (3.1%) selected patients with severe COVID-19 and at least 2 risk factors for venous thromboembolism (VTE) and in all patients with previous history of VTE. Follow-up coagulation profile in 85 patients showed that changes over time had a tendency towards normalization irrespectively of the initiation of anticoagulant thromboprophylaxis. No thrombotic complications were observed 3 months upon discharge. CONCLUSIONS: Although abnormal findings in coagulation profile were very common, they were not associated with risk for VTE even in severe cases. A trend of normalization early in the course of the disease was observed regardless of the use of anticoagulant thromboprophylaxis.

Autoimmune pulmonary alveolar proteinosis in children.

In childhood, a multitude of causes lead to pulmonary alveolar proteinosis (PAP), an excessive surfactant accumulation in the alveolar space, limiting gas exchange. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) causing autoimmune PAP, the principal aetiology in adults, are rare. In this first case series on autoimmune PAP, we detail the presentation and management issues of four children. Whereas three children presented insidiously with progressive dyspnoea, one was acutely sick with suspected pneumonia. During management, one patient was hospitalised with coronavirus disease 2019, noninvasively ventilated, and recovered. All treatment modalities known from adults including whole-lung lavage, augmentation of GM-CSF by inhaled GM-CSF, removal of neutralising antibody by plasmapheresis and interruption of antibody production using rituximab were considered; however, not all options were available at all sites. Inhaled GM-CSF appeared to be a noninvasive and comfortable therapeutic approach. The management with best benefit-to-harm ratio in autoimmune PAP is unknown and specialised physicians must select the least invasive and most effective treatment. To collect this cohort in a rare condition became feasible as patients were submitted to an appropriate registry. To accelerate the authorisation of novel treatments for autoimmune PAP, competent authorities should grant an inclusion of adolescents into trials in adults.

Angiotensin-Converting Enzyme 2 (ACE2) As a Novel Biorecognition Element in A Cell-Based Biosensor for the Ultra-Rapid, Ultra-Sensitive Detection of the SARS-CoV-2 S1 Spike Protein Antigen

Antigen screening for the SARS-CoV-2 S1 spike protein is among the most promising tools for the mass monitoring of asymptomatic carriers of the virus, especially in limited resource environments. Herewith, we report on the possible use of the angiotensin-converting enzyme 2 (ACE2), the natural receptor and entry point of the virus, as a biorecognition element for the detection of the S1 antigen combined with an established bioelectric biosensor based on membrane-engineered cells. The working principle of our approach is based on the measurable change of the electric potential of membrane-engineered mammalian cells bearing ACE2 after attachment of the respective viral protein. We demonstrate that sensitive and selective detection of the S1 antigen is feasible in just three min, with a limit of detection of 20 fg/mL. In a preliminary clinical application, positive patient-derived samples were identified with a 87.9% score compared to RT-PCR. No cross-reactivity was observed against a wide range of nucleocapsid protein concentrations. The novel biosensor is embedded in a commercially ready-to-use testing platform, complete with the consumable immobilized cell–electrode interface and a portable read-out device operable through smartphone or tablet. In addition, the possible application of the system for the high throughput screening of potential pharmacological inhibitors of the ACE2 receptor-S1 RBD interaction is discussed.

Daily Behaviors, Worries and Emotions in Children and Adolescents with ADHD and Learning Difficulties during the COVID-19 Pandemic.

The aim of the present study was to investigate the effects of the coronavirus crisis on behavioral and emotional parameters in children and adolescents with ADHD and Learning Difficulties. A total of 101 children, 5-18 years old, were included in the study, 63 (44 boys) of which were diagnosed with ADHD and learning difficulties (ADHD/LD) and 38 were healthy children (19 boys). The CRISIS questionnaire for parents/caregivers was used. The questionnaire was completed during the first national lockdown in Greece and the data referred to two time-points: 3 months before, and the past 2 weeks. A significant deterioration in the "Emotion/Worries (EW)" symptoms was observed during the pandemic in the control group (2.62 ± 0.16 vs. 2.83 ± 0.18, p < 0.001). No such differences were noted in the ADHD group: 3.08 ± 0.25 vs. 3.12 ± 0.29, p = 0.12. Provision of educational and activities support was related to increased EW before the crisis. In ADHD/LD children, higher parental education and child's younger age were related to increased symptoms of EW. In the entire group, previous mental health conditions, increasing stress due to restrictions, and increased COVID-related worries were positively associated with the EW symptoms during the crisis. Less affected relations with friends and less reduction in contact with people outside the home were negatively related with EW during the crisis. The study revealed specific parameters that negatively affected the emotional and behavioral variables of children with ADHD and learning difficulties.

Clinical management of patients with genetic obesity during COVID-19 pandemic: position paper of the ESE Growth & Genetic Obesity COVID-19 Study Group and Rare Endo-ERN main thematic group on Growth and Obesity.

This article aims to provide guidance on prevention and treatment of COVID-19 in patients with genetic obesity. Key principals of the management of patients with genetic obesity during COVID-19 pandemic for patients that have contracted COVID-19 are to be aware of: possible adrenal insufficiency (e.g., POMC deficiency, PWS); a more severe course in patients with concomitant immunodeficiency (e.g., LEP and LEPR deficiency), although defective leptin signalling could also be protective against the pro-inflammatory phenotype of COVID-19; disease severity being masked by insufficient awareness of symptoms in syndromic obesity patients with intellectual deficit (in particular PWS); to adjust medication dose to increased body size, preferably use dosing in m2; the high risk of malnutrition in patients with Sars-Cov2 infection, even in case of obesity. Key principals of the obesity management during the pandemic are to strive for optimal obesity management and a healthy lifestyle within the possibilities of the regulations to prevent weight (re)gain and to address anxiety within consultations, since prevalence of anxiety for COVID-19 is underestimated.