AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report.

Introduction: The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion: Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.

Trends and cyclic variation in the incidence of childhood type 1 diabetes in two Italian regions over 33 years and during the COVID-19 pandemic.

AIM: There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here, we analysed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data. MATERIALS AND METHODS: This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models. RESULTS: There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4-4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: -1.3 to 2.4). There was a significant 4-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0-30.9) was significantly higher than expected (19.5, 95% CI: 17.6-21.4; p = .010). CONCLUSION: Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID-19 on new-onset type 1 diabetes in children.

Reduced burden of antibiotic prescription in an italian pediatric primary care clinic during the first wave of COVID-19 pandemic: a shot in the arm for antimicrobial resistance?

Rates of antibiotic-resistant bacteria have increased worldwide over recent years, but the Italian Institute of Health reported a disruption to this trend in 2021 compared with 2020. Children are often recipients of unnecessary antibiotic prescriptions, especially for respiratory tract infections (RTIs). During the initial phase of the COVID-19 pandemic, common RTIs substantially decreased, so it is conceivable that antibiotic prescriptions also reduced during this time. To test this hypothesis, we retrospectively collected data on all visits to a pediatric primary care clinic in Northern Italy from February 20, 2020 to June 2, 2020 and compared data with the same period in 2019. We evaluated the antibiotic prescription rate according to the diagnosis at discharge. While the total number of visits significantly decreased (1335 in 2020 vs. 4899 in 2019), there was only a slight reduction in the antibiotic prescription rate (1039 in 2019, 21.2%, vs. 272 in 2020, 20.4%). However, this corresponded to a 73.8% decrease in the total number of antibiotic prescriptions, with antibiotics for RTI accounting for 69% of the total reduction. It is possible that, at the larger scale, reduced antibiotic prescription in pediatrics during the COVID-19 pandemic resulted in a slight reduction in antimicrobial resistance.

Clinical and Forensic Aspects of the Management of Child Abuse: The Experience of the Paediatric Emergency Department in Novara, North-West Italy.

BACKGROUND: Child abuse is an endemic phenomenon that refers to any form of violence aimed at children and adolescents. The Emergency Room is often the entry point to healthcare for the abused child. METHODS: This is a cross-sectional study including minors, aged 0-18 years, of all genders, who experienced any form of violence examined at the Paediatric Emergency Department of the 'Maggiore della Carità' Hospital in Novara (North-West Italy) between 1 January 2017 to 31 December 2021. Data were extrapolated by looking at the diagnosis at discharge. A comparison of the different variables collected was made between the pre-COVID-19 period and the COVID era. RESULTS: 120 minors presented to the paediatric emergency room seeking help for violence. The average age was 10 years, 55% of the victims were male and 75% of them were Italian. In the pre-COVID period, the number of presentations for abuse was 62, while in the COVID period it was 58 with an increase of peer violence (from 38.71% to 62.07%) and with a statistically significant impact of the pandemic on the phenomenon (p-value < 0.00001). In general, peer violence accounts for 50% of the cases reviewed and resulted in fewer reports to the judicial authority and requests for forensic advice. CONCLUSION: The SARS-CoV-2-related pandemic has had an impact on total emergency room admissions and the types of abuse perpetrated.

#Stayathome If You Have a Cold: High SARS-CoV-2 Salivary Viral Loads in Pediatric Patients with Nasopharyngeal Symptoms.

The choice of the best SARS-CoV-2 detection approach is crucial to predict which children with SARS-CoV-2 are at high risk of spreading the virus in order to manage public health measures and policies. In this prospective observational study of 35 children admitted to the Pediatric Emergency Departments of two tertiary hospitals in Northern Italy who tested positive for SARS-CoV-2 by standard RT-PCR in nasopharyngeal swab (NPS), we evaluated their presenting symptoms according to their salivary viral load (SVL) determined by droplet digital PCR (ddPCR). Despite an overall low concordance between SARS-CoV-2 detected by salivary ddPCR and NPS RT-PCR (54.3%), when only patients with nasopharyngeal symptoms were analyzed, the sensitivity of ddPCR in saliva specimens increased to 71.4%, and over half of these patients had high SVL (>105 copies/mL), which was significantly more frequent than in children without nasopharyngeal symptoms (57.1% vs. 14.3%, OR = 8, CI 95% 1.28−50.03, p = 0.03). All asymptomatic children had low SVL values. Our findings support the hypothesis that children with nasopharyngeal symptoms are at higher risk of spreading SARS-CoV-2 due to their high SVL and, conversely, asymptomatic children are unlikely to spread the virus due to their low SVL, regardless of their NPS positivity.

The Importance of RSV Epidemiological Surveillance: A Multicenter Observational Study of RSV Infection during the COVID-19 Pandemic.

The restrictive measures adopted worldwide against SARS-CoV-2 produced a drastic reduction in respiratory pathogens, including RSV, but a dramatic rebound was thereafter reported. In this multicenter retrospective observational study in 15 Pediatric Emergency Departments, all children <3 years old with RSV infection admitted between 1 September and 31 December 2021 were included and compared to those admitted in the same period of 2020 and 2019. The primary aim was to evaluate RSV epidemiology during and after the COVID-19 pandemic peak. The secondary aims were to evaluate the clinical features of children with RSV infection. Overall, 1015 children were enrolled: 100 in 2019, 3 in 2020 and 912 in 2021. In 2019, the peak was recorded in December, and in 2021, it was recorded in November. Comparing 2019 to 2021, in 2021 the median age was significantly higher and the age group 2-3 years was more affected. Admissions were significantly higher in 2021 than in 2020 and 2019, and the per-year hospitalization rate was lower in 2021 (84% vs. 93% in 2019), while the duration of admissions was similar. No difference was found in severity between 2019-2020-2021. In conclusion, after the COVID-19 pandemic, an increase in RSV cases in 2021 exceeding the median seasonal peak was detected, with the involvement of older children, while no difference was found in severity.

High rates of neonatal polycythemia and hyperbilirubinemia during the first phase of COVID-19 pandemic in Italy: a single-center experience.

In our third-level Neonatal Unit in Northern Italy, we recorded a high rate of neonatal hyperbilirubinemia requiring phototherapy in March-November 2020, during the first phase of COVID-19 pandemic, compared to the previous year (198/1348, 14.2%, vs 141/1432, 9.8%, p = 0.0004). Supposing it could be the result of neonatal polycythemia, we evaluated capillary hematocrit (Hct) and the rate of hyperbilirubinemia in all newborns ≥36 weeks gestational age born in December 2020. Out of 73 neonates, 37 had Hct ≥65% (50.7%). However, as capillary blood samples may overestimate Hct by 5-15%, even downsizing all values by 15%, Hct was still ≥65% in 9/73 neonates (12.3%), much higher than 0.4-5% prevalence of polycythemia reported in healthy newborns. All those newborns were singleton and healthy, with no clinical signs of hyperviscosity and no underlying factors predisposing to polycythemia. Out of 73 newborns, 13 (17.8%) developed hyperbilirubinemia requiring phototherapy. Their mean Hct value was 66.3 ± 8.2%. Since hyperbilirubinemia is common in the offspring of women with SARS-CoV-2 infection and we recorded increased rates of neonatal hyperbilirubinemia in the first phase of COVID-19 pandemic, it could be hypothesized that even asymptomatic Sars-CoV2 infection during pregnancy might cause placental vascular malperfusion, eliciting polycythemia in the fetus as a compensatory response, that could be the link between COVID-19 in the mothers and hyperbilirubinemia in the newborns.

Case Report: Role of Ketone Monitoring in Diabetic Ketoacidosis With Acute Kidney Injury: Better Safe Than Sorry.

Background: Type 1 Diabetes (T1D) is a well-known endocrinological disease in children and adolescents that is characterized by immune-mediated destruction of pancreatic ß-cells, leading to partial or total insulin deficiency, with an onset that can be subtle (polydipsia, polyuria, weight loss) or abrupt (Diabetic Keto-Acidosis, hereafter DKA, or, although rarely, Hyperosmolar Hyperglycemic State, hereafter HHS). Severe DKA risk at the onset of T1D has recently significantly increased during the SARS-CoV-2 pandemic with life-threatening complications often due to its management. DKA is marked by low pH (<7.3) and bicarbonates (<15 mmol/L) in the presence of ketone bodies in plasma or urine, while HHS has normal pH (>7.3) and bicarbonates (>15 mmol/L) with no or very low ketone bodies. Despite this, ketone monitoring is not universally available, and DKA diagnosis is mainly based on pH and bicarbonates. A proper diagnosis of the right form with main elements (pH, bicarbonates, ketones) is essential to begin the right treatment and to identify organ damage (such as acute kidney injury). Case Presentations: In this series, we describe 3 case reports in which the onset of T1D was abrupt with severe acidosis (pH < 7.1) in the absence of both DKA and HHS. In a further evaluation, all 3 patients showed acute kidney injury, which caused low bicarbonates and severe acidosis without increasing ketone bodies. Conclusion: Even if it is not routinely recommended, a proper treatment that included bicarbonates was then started, with a good response in terms of clinical and laboratory values. With this case series, we would like to encourage emergency physicians to monitor ketones, which are diriment for a proper diagnosis and treatment of DKA.

Corrigendum: MIS-C Treatment: Is IVIG Always Necessary?

[This corrects the article DOI: 10.3389/fped.2021.753123.].

MIS-C Treatment: Is IVIG Always Necessary?

Background: MIS-C is a potentially severe inflammatory syndrome associated with SARS-CoV-2 exposure. Intravenous immunoglobulin (IVIG) is considered the first-tier therapy, but it implies infusion of large fluid volumes that may worsen cardiac function. Patients and Methods: Since April 2020, we have developed a treatment protocol that avoids the infusion of IVIG as first-line therapy in the early phase of MIS-C. In this study, we retrospectively analyzed a cohort of consecutive patients treated according to this protocol between 01/04/2020 and 01/04/2021. Results: In the last year, 31 patients have been treated according to the protocol: 25 with high-dose pulse MP (10 mg/kg) and 6 with 2 mg/kg. 67.7% of the patients responded to the initial treatment, while the others needed a step-up, either with Anakinra (25.8%) or with MP dose increase (6.5%). IVIG was administered in four patients. Overall, only one patient (3.2%) needed ICU admission and inotropic support; one patient developed a small coronary artery aneurysm. Conclusions: Timely start of MP therapy and careful fluid management might improve the outcomes of MIS-C patients.

Changing Admission Patterns in Pediatric Emergency Departments during the COVID-19 Pandemic in Italy Were Due to Reductions in Inappropriate Accesses.

During the initial phase of the national lockdown, we found that there were sharp decreases in admissions to two pediatric emergency departments (EDs) in northern Italy (Cremona and Novara). Here we present a detailed analysis of these admission patterns and types of admissions over a longer timeframe. ED admissions data were anonymously extracted from the departmental management software. Admissions data from 2019 and 2020 were analyzed and compared separately for each ED and combined. There was a 73.2% decrease in total admissions compared with the same period in 2019. With respect to admission diagnoses, there was a significant (p < 0.001) drop in infectious (-51%), respiratory (-25.5%), and nervous systems diseases (-50%) and injuries and poisoning (-17%) but not endocrine, metabolic, neoplastic, circulatory, or musculoskeletal diseases. White codes (patients with minor injuries for whom ED medical care is not required) significantly decreased by 56.3% (p < 0.001). Even if the COVID-19 pandemic represented an enormous healthcare burden in Italy, especially during the first months of the pandemic (late February to May), the workload of pediatric EDs was significantly reduced, especially for unnecessary accesses (white codes).

A Global Overview of COVID-19 Research in the Pediatric Field: Bibliometric Review.

BACKGROUND: Since the beginning of the COVID-19 pandemic, a great number of papers have been published in the pediatric field. OBJECTIVE: We aimed to assess research around the globe on COVID-19 in the pediatric field by bibliometric analysis, identifying publication trends and topic dissemination and showing the relevance of publishing authors, institutions, and countries. METHODS: The Scopus database was comprehensively searched for all indexed documents published between January 1, 2020, and June 11, 2020, dealing with COVID-19 in the pediatric population (0-18 years). A machine learning bibliometric methodology was applied to evaluate the total number of papers and citations, journal and publication types, the top productive institutions and countries and their scientific collaboration, and core keywords. RESULTS: A total of 2301 papers were retrieved, with an average of 4.8 citations per article. Of this, 1078 (46.9%) were research articles, 436 (18.9%) were reviews, 363 (15.8%) were letters, 186 (8.1%) were editorials, 7 (0.3%) were conference papers, and 231 (10%) were categorized as others. The studies were published in 969 different journals, headed by The Lancet. The retrieved papers were published by a total of 12,657 authors from 114 countries. The most productive countries were the United States, China, and Italy. The four main clusters of keywords were pathogenesis and clinical characteristics (keyword occurrences: n=2240), public health issues (n=352), mental health (n=82), and therapeutic aspects (n=70). CONCLUSIONS: In the pediatric field, a large number of articles were published within a limited period on COVID-19, testifying to the rush to spread new findings on the topic in a timely manner. The leading authors, countries, and institutions evidently belonged to the most impacted geographical areas. A focus on the pediatric population was often included in general articles, and pediatric research about COVID-19 mainly focused on the clinical features, public health issues, and psychological impact of the disease.