COVID-19 and diabetes in children.

This review describes the impact of coronavirus disease 2019 (COVID-19) in children and adolescents, investigating changes in diabetes presentation during the COVID-19 pandemic, possible links between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and diabetes, and mechanisms of pancreatic ß-cell destruction. Although glycemic control in individuals with already known diabetes mellitus did not worsen during the pandemic, there was a worrying increase in diabetic ketoacidosis in children with new-onset diabetes, probably due to containment measures and delayed access to emergency departments. Moreover, new evidence suggests that SARS-CoV-2 has the capacity to directly and indirectly induce pancreatic ß-cell destruction, and the risk of newly diagnosed diabetes after COVID-19 increased in both children and adults. While long-term studies continue to follow children with SARS-CoV-2 infection, this review discusses available findings on the relationship between COVID-19 and diabetes. It is important to emphasize the need to maintain close links between families of children with chronic conditions and their pediatricians, as well as to promote early access to healthcare services, in order to reduce dangerous delays in diabetes diagnosis and prevent diabetic ketoacidosis.

Case report: Increased troponin level in 125 children during COVID-19.

Introduction: Increase in cardiac biomarkers during Coronavirus disease 2019 (COVID-19) was frequent regardless of the presence of myocarditis and multisystem inflammatory syndrome in children (MIS-C). Several studies described MIS-C, but few papers evaluated cardiac manifestations in children with SARS-CoV-2 infection without MIS-C and investigated the role of troponin in absence of electrocardiogram (ECG) and echocardiographic alterations. The aim of this case series is to describe the cardiac manifestations during COVID-19 in children, trying to explain the meaning of laboratory findings during COVID-19, especially of increased troponin. Materials and methods: We conducted a retrospective case series of children aged <18 years admitted at the Department of Pediatrics, University of Chieti, for SARS-CoV-2 infection between 1st March 2020 and 31th July 2022. All patients with documented SARS-CoV-2 infection underwent a laboratory evaluation at admission. Children with increased troponin I and/or BNP underwent electrocardiographic and echocardiographic exams. Results: 125 children were admitted for SARS-CoV-2 infection to our Department of Pediatrics, of whom 17 (13.6% of cases) with different patterns of cardiac involvement. Specifically, 5 subjects (4.0% of admitted children) were diagnosed as MIS-C and 12 children (9.6%) manifested a cardiac involvement in terms of increased troponin with or without ECG and echocardiography anomalies. Troponin, C-reactive protein, procalcitonin and BNP values resulted higher in patients with MIS-C compared to patients without MIS-C. Furthermore, patients with MIS-C had higher neutrophils and lower lymphocytes compared to patients without MIS-C. ECG abnormalities were found in 4/5 patients with MIS-C and in 2/12 patients without MIS-C. Echocardiographic anomalies were found in all patients with MIS-C, especially in terms of valve regurgitation and ejection fraction reduction and in 2/12 patients without MIS-C, especially in terms of pericardial effusion. Despite high troponin levels, children presented a favorable clinical evolution. Conclusion: The increase in troponin level in children with COVID-19 could also be due to respiratory causes or a massive inflammatory state. In our case series, patients with increased troponin associated to COVID-19 presented a favorable clinical course with clinical and laboratory remission almost always within 7 days.

Endocrine Disruptor Chemicals and Children's Health.

We are all exposed to endocrine-disrupting chemicals (EDCs) starting from embryonic life. The fetus and child set up crucial developmental processes allowing adaptation to the environment throughout life: they are extremely sensitive to very low doses of hormones and EDCs because they are developing organisms. Considering the developmental origin of well-being and diseases, every adult organism expresses consequences of the environment in which it developed. The molecular mechanisms through which the main EDCs manifest their effects and their potential association with endocrine disorders, such as diabetes, obesity, thyroid disease and alteration of adrenal hormones, will be reviewed here. Despite 40 years having passed since the first study on EDCs, little is yet known about them; therefore, our purpose is to take stock of the situation to establish a starting point for further studies. Since there is plenty of evidence showing that exposure to EDCs may adversely impact the health of adults and children through altered endocrine function-suggesting their link to endocrinopathies-it is essential in this context to bear in mind what is already known about endocrine disruptors and to deepen our knowledge to establish rules of conduct aimed at limiting exposure to EDCs' negative effects. Considering that during the COVID-19 pandemic an increase in endocrine disruptor effects has been reported, it will also be useful to address this new phenomenon for better understanding its basis and limiting its consequences.

Early and precocious puberty during the COVID-19 pandemic.

During the year 2020, the COVID-19 pandemic rapidly became a severe health emergency worldwide. In order to contrast the spread of the novel SARS-CoV-2, many countries implemented extraordinary restrictive measures, such as a strict lockdown and school closures. The pandemic had a great impact on children and adolescents' daily life, leading to a much more sedentary lifestyle, to larger use of electronic devices and to an increase in stress-related symptoms. These conspicuous changes acted as disruptors of children's normal development. Since the beginning of the pandemic, many studies reported an increase in the number of precocious puberty cases as well as a faster progression rate of puberty itself, if compared to the pre-pandemic years. In this review, our aim was to evaluate the incidence of new cases of early and precocious puberty during the COVID-19 pandemic, analyzing variations in the timing of puberty and in pubertal progression rate, and to investigate the role of environmental and lifestyle factors during the pandemic in modulating the physiopathology of pubertal development. While a direct effect of SARS-CoV-2 infection remains, at the moment, a remote hypothesis, both physical and psychological factors related to the pandemic seem to have a role in triggering GnRH pulsatile secretion leading to earlier pubertal onset. It is indeed important to stress the need to clarify the exact role of COVID-19 in early pubertal onset comparing data from all over the world; long-term comprehensive studies are also pivotal to explain whether this phenomenon will continue while we resume pre-pandemic habits.

A 5-Year-Old Child with a Deep Neck Abscess Complicated by Laryngeal Obstruction.

Deep neck space infections (DNSI) are defined as infections in the potential spaces and fascial planes of the neck. We show the clinical case of a retro and para-pharyngeal abscess in a healthy 5-year-old child complicated by compression and dislocation of the larynx with marked airway caliber reduction and potentially fatal extension up to the mediastinal aditus. DNSI can occur at any age and, due to its rapid progression, requires immediate treatment in children. In healthy children, concurrent abscesses in separate neck spaces are rare. DNSI recurrence should alert the physician to the possibility of a congenital problem, and if imaging fails, laryngoscopy may be the best diagnostic technique.

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020.

Aim/Hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019. Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019. Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively). Conclusions/Interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.

The bad rainbow of COVID-19 time: effects on glucose metabolism in children and adolescents with obesity and overweight.

BACKGROUND: COVID-19 restriction measurements have enhanced the obesity status in the pediatric population which might further contribute to obesity-related glucose-insulin metabolism alterations. Therefore, we retrospectively compared anthropometric and OGTT data on children with obesity during the 13 years before and during the COVID-19 pandemic. SUBJECTS/METHODS: Data from 741 children with obesity and overweight were retrieved and clustered into seven groups starting from year 2008-2009 until 2020-2021. Differences in anthropometric measurements and glucose/insulin metabolism were evaluated between the different groups. RESULTS: Children with overweight and obesity in the COVID-19 restriction group did not present increased values of SDS-Body Mass Index (BMI). Significantly higher values for Waist Circumference (WC), SDS-WC, Waist/Height ratio (WHtR), and body mass fat were detected in these children (all P < 0.01). Fasting glycaemia, glucose, and insulin excursions were significantly higher compared to pre- pandemic children (all P < 0.01). Insulin resistance was higher while insulin secretion was lower (all P < 0.01) determining a significantly higher percentage of impaired glucose tolerance in the COVID-19 restriction group (P < 0.002). Furthermore, High-Density Lipoprotein (HDL) cholesterol was significantly lower (P < 0.01) and SDS for systolic and diastolic blood pressure values were significantly higher (P = 0.03 and P = 0.02, respectively). CONCLUSIONS: COVID-19 restriction measurements determined profound alterations in glucose and insulin metabolism in children with obesity and overweight. Urgent strategies are needed in order to reverse COVID-19 restriction measures' effects on glucose and insulin metabolism.

Liver Steatosis: A Marker of Metabolic Risk in Children

Obesity is one of the greatest health challenges affecting children of all ages and ethnicities. Almost 19% of children and adolescents worldwide are overweight or obese, with an upward trend in the last decades. These reports imply an increased risk of fat accumulation in hepatic cells leading to a series of histological hepatic damages gathered under the acronym NAFLD (Non-Alcoholic Fatty Liver Disease). Due to the complex dynamics underlying this condition, it has been recently renamed as ‘Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)’, supporting the hypothesis that hepatic steatosis is a key component of the large group of clinical and laboratory abnormalities of Metabolic Syndrome (MetS). This review aims to share the latest scientific knowledge on MAFLD in children in an attempt to offer novel insights into the complex dynamics underlying this condition, focusing on the novel molecular aspects. Although there is still no treatment with a proven efficacy for this condition, starting from the molecular basis of the disease, MAFLD’s therapeutic landscape is rapidly expanding, and different medications seem to act as modifiers of liver steatosis, inflammation, and fibrosis.

Peculiar characteristics of new-onset Type 1 Diabetes during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic period is having a strong impact on the management of diabetes as well as other chronic diseases as shown by the most severe clinical presentation at onset. The aim of this study was to evaluate the severity of diabetic ketoacidosis (DKA) in youth with newly diagnosed type 1 diabetes in "Santissima Annunziata Hospital" (Chieti, Italy) during COVID-19 pandemic in comparison to the five previous years. METHODS: A retrospective population-based incidence study was performed. Data were obtained from hospital records of 172 patients with new onset type 1 diabetes divided into two groups according to the diagnosis: Group I, between January 2015 and February 2020; Group II, between March 2020 and April 2021. Data regarding anthropometric, socio-economic and laboratory test were analyzed. DKA (pH < 7.30) and different severity of the disease (severe pH < 7.10; moderate pH < 7.20, mild pH < 7.30) were evaluated. A Spearman correlation between pH values and the main variables of interest was performed. RESULTS: DKA frequency was increased by 19 percentage in Group II compared to Group I (55% vs 36%; P = 0.03) with a significant increased risk of severe DKA cases compared to the previous five years (severe DKA 22.5% vs. 8.4%, P = 0.01). pH values were significantly related with HbA1c, blood glucose and c-peptide values in all groups. In addition, in Group II but not in Group I, pH values correlated with Triglycerides and TG/HDL cholesterol ratio. CONCLUSIONS: During COVID-19 pandemic the risk of more severe clinical presentation of type 1 diabetes at onset is increased. The correlation with lipid profile might suppose an additional effect of lifestyle changes beside the delay in the diagnosis. Modifications of health care system need to be implemented during this peculiar situation in order to avoid such a relevant complication at onset.

Emergency Department Visits for allergy related-disorders among children: experience of a single Italian hospital during the first wave of the COVID-19 pandemic.

Introduction: The aim of this study was to compare the number of the Pediatric Emergency Department (PED) visits for young allergic patients with respiratory or cutaneous symptoms during the first wave of the coronavirus disease 19 (COVID-19) pandemic in 2020 with the same period in 2019, evaluating the percentage of positive cases to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We carried out a retrospective analysis using data from young patients who visited the PED with cutaneous or respiratory symptoms in the period from 20th February to 12th May of the years 2020 and 2019. Data on allergy and COVID-19 nasal swab were also collected. We observed eleven (28.2%) PED visits for allergic patients with respiratory or cutaneous symptoms for the period from 20th February to 12th May of the year 2020 and ninety-three (31.8%) PED visits for the same time frame of the year 2019 (p=0.645). Only a two-month-old child out of 39 patients with non-allergic respiratory or cutaneous symptoms resulted positive for SARS-CoV-2. Specifically, we found for all the PED visits: 21 (7.2%) in 2019 vs 2 (5.1%) in 2020 for patients with urticaria/angioedema or atopic dermatitis (p=0.634); 3 (1.0%) in 2019 vs 3 (7.7%) in 2020 for patients with anaphylaxis (p=0.003); 19 (6.5%) in 2019 vs 2 (5.1%) in 2020 for those with asthma (p=0.740); 11(3.8%) in 2019 vs 1(2.6%) in 2020 for those with lower respiratory diseases, excluding asthma (p=0.706); 39(13.4%) in 2019 vs 3 (7.7%) in 2020 for those with upper respiratory diseases (URDs) (p=0.318). We also showed a substantial decrease (~80%) in all PED visits compared with the same time frame in 2019 (absolute number 263 vs 1,211, respectively). Among all the PED visits a significant reduction was mostly found for URDs [155 (12.8%) in 2019 vs 17 (6.5%) in 2020; p=0.045)]. The total number of PED visits for allergic patients with respiratory or cutaneous symptoms dropped precipitously in 2020. It is very tricky to estimate whether it was a protective action of allergy or the fear of contagion or the lockdown or a reduction in air pollution that kept children with allergy from visiting the PED. Further studies are needed to better understand the impact of underlying allergies on COVID-19 susceptibility and disease severity.

Usefulness of Lung Ultrasound in Paediatric Respiratory Diseases.

Respiratory infection diseases are among the major causes of morbidity and mortality in children. Diagnosis is focused on clinical presentation, yet signs and symptoms are not specific and there is a need for new non-radiating diagnostic tools. Among these, lung ultrasound (LUS) has recently been included in point-of-care protocols showing interesting results. In comparison to other imaging techniques, such as chest X-ray and computed tomography, ultrasonography does not use ionizing radiations. Therefore, it is particularly suitable for clinical follow-up of paediatric patients. LUS requires only 5-10 min and allows physicians to make quick decisions about the patient's management. Nowadays, LUS has become an early diagnostic tool to detect pneumonia during the COVID-19 pandemic. In this narrative review, we show the most recent scientific literature about advantages and limits of LUS performance in children. Furthermore, we discuss the major paediatric indications separately, with a paragraph fully dedicated to COVID-19. Finally, we mention potential future perspectives about LUS application in paediatric respiratory diseases.

Case Report: Mitral Valve Involvement and First-Degree Atrial-Ventricular Block in Two Patients With Multisystem Inflammatory Syndrome in Children.

COVID-19 seems to be less frequent and severe in children compared to adults. Despite the very few symptoms usually found in children, great attention was recorded when in April 2020 a hyperinflammatory process in children with fever and multiorgan involvement after a paucisymptomatic COVID infection was reported. The United States Centers for Disease Control and the World Health Organization recognized and defined this syndrome as "Multisystem Inflammatory Syndrome in Children (MIS-C)." We describe two cases of MIS-C presenting with fever, cutaneous rash, and a mild cardiac involvement expressed with a transient mitral valve involvement and a first-degree atrioventricular block. Acute treatment was managed with intravenous immunoglobulin, oral aspirin, and intravenous corticosteroids reaching consequent good outcome. Clinical characteristics, treatment management, follow-up, and long-term evolution of children with MIS-C are still poorly defined. Further research is needed to better understand the pathogenesis of this newly described condition, to validate a high-level recommended therapy and a specific therapy tapering timings.

Evaluation of sleep quality and anxiety in Italian pediatric healthcare workers during the first wave of COVID-19 pandemic.

OBJECTIVE: The aim of this study was to evaluate sleep quality and psychological effects on pediatric healthcare workers during the first wave of COVID-19 epidemic in Italy and to evaluate differences between primary and secondary care operators. Pediatric healthcare workers were involved in an online survey to assess sleep quality, stress and anxiety level, self-efficacy and social support in Italian pediatric healthcare workers during COVID-19 pandemic. RESULTS: We found that 67.4% of our sample suffered from sleep disturbance and 19.4% of subjects suffered from anxiety. Lower values of anxiety and social support were found in primary care staff compared to secondary care one. The associations between healthcare professional figures (being primary or secondary care operators) and mental health outcomes were not statistically significant. However, sex, age and having a SARS-CoV-2 infected relative/friend had an independent effect on mental health outcomes. It is crucial to provide social and psychological support to pediatric healthcare workers. A tailored psychological screening would be desirable for female healthcare workers and for those who have a SARS-CoV-2 infected relative/friend.

An Outbreak of Kawasaki-like Disease in children during SARS-CoV- 2 Epidemic: No Surprise?

BACKGROUND AND AIM: Kawasaki disease is an acute systemic febrile illness of unknown aetiology, which usually affects children under 5 years of age. It is well known that Kawasaki disease is one of the most common causes of acquired heart diseases in children in the developed countries. Many studies, have suggested that heterogeneous infectious agents, such as common viruses, may trigger Kawasaki disease in young children with genetic background.  Nowadays we are facing a pandemic caused by a Novel Coronavirus named SARS-CoV-2. Consequently, it could be possible that once exposed to this new coronavirus, some children, genetically predisposed, may mount an exaggerated inflammatory response which clinically manifests as Kawasaki Disease. METHODS: from January to May 2020 a systematic search was performed on Pubmed for the following search terms: "COVID-19", "children", "SARS-CoV-2", "complications", "Kawasaki disease", "cytokine storm". RESULTS: Usually, infants and children present milder symptoms of SARS-CoV-2 disease with a better outcome than adults. At variance, some children may be genetically disposed to a more robust inflammatory response to SARS-CoV-2, similar to Kawasaki disease. In fact, Kawasaki disease is the result of an abnormal immune response, in susceptible children, to an external trigger such as an infection. Thus, according to the pathogenesis of Kawasaki disease, paediatricians may expect an increase in cases of Kawasaki disease during the COVID-19 pandemic.

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. OBJECTIVE: We explored the clinical management of inpatients with COVID-19 in Italy. METHODS: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. RESULTS: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. CONCLUSIONS: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Novel coronavirus infection and children.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS: We searched Pubmed, from January to April 2020, for the following search terms: "COVID-19", "children", "SARS-COV2", "complications", "epidemiology", "clinical features", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS: Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.