Essential headaches in developmental age: What is changed before, during and after the lockdown for COVID-19 pandemic. Clinical study.

Introduction: Essential headache is one of the main causes of pain in children, and has an important impact on their quality of life. In children with essential headaches play an important role in both triggers like stress, excessive use of video terminals, or physical fatigue but also comorbidities like anxiety, depression, and sleep disturbances. CoViD-19 Pandemic was very stressful, especially for children, and amplified all headache triggers and comorbidities. Study objective: In this work, we studied the aspects concerning the headache,lifestyle, habits, and mental health of children before, during, and after the lockdown and the differences between some categories (selected by age, gender, and headache status before the lockdown). Methods: This study was conducted on 90 patients with primary headaches followed at the AOUP Neuropediatrics Clinic from January 2018 to March 2022. Participants answered a questionnaire of 21 questions. For every question, the answer was divided into three periods: before, during, or after the lockdown. All dates have been converted and inserted into a database and we used SPSS technology for statistical analysis. Results: In our study, 51,1% were females and 48,9% were males and there was a prevalence of adolescents (56,7%) compared to children from 5 to 11 years (43,3%). Regarding the headache onset, 77,7% of patients started to suffer from headaches before 10 years, moreover, 68,9% had familiarity with the headache. Using Cohen's K- Concordance Test, we performed a Concordance Analysis, studying the questions in the three periods above mentioned: considering headache characteristics there is poor concordance about the trend of headache; modest concordance (K: 0,2-0,4) about the frequency and the type (migraine or tension headache); moderate concordance (K: 0,41-0,61) about the acute use of analgesic. Analyzing lifestyle the lockdown had a significant impact on sports (practiced much less) and on the use of video terminals (used much more). Conclusion: The pandemic and lockdown aren't events that led to strong and unidirectional responses in patients, there is great variability in the answers about headache, lifestyle, and psychology, and each patient had individualized reactions. However, these considerations are not applied to physical activity and the use of video terminals, because both have been inevitably modified by the pandemic situations and so were not affected by subjective influence.

Neurovisual Manifestations in Children with Mild COVID-19: An Association to Remember.

Neurovisual involvement has been reported in a number of patients with severe SARS-CoV-2 disease (COVID-19), mainly among adult patients. In children, such involvement has been reported in rare cases, often in those presenting with severe forms of COVID-19. The aim of this work is to explore the association between mild COVID-19 and neurovisual manifestations. We report the cases of three previously healthy children who developed neurovisual manifestations following mild acute COVID-19, analysing the clinical phenotype, the latency between the onset of acute COVID-19 and neurovisual involvement, and the kinetic of resolution. Our patients developed different clinical patterns, including visual impairment and ophthalmoplegia. In two cases, these clinical features occurred during acute COVID-19, while in the third patient their development was delayed after 10 days from disease onset. Furthermore, the dynamics of resolution were different, with one patient showing remission after 24 hours, the second after 30 days, and the third showing persistence of the strabismus after 2 months of follow-up. The spreading of COVID-19 among the paediatric population will probably lead to an increase of atypical disease forms, including those presenting with neurovisual involvement. Therefore, a better knowledge of the pathogenic and clinical features of these manifestations is warranted.

Case Report: MIS-C With Prominent Hepatic and Pancreatic Involvement in a Vaccinated Adolescent - A Critical Reasoning.

Multisystem inflammatory syndrome in children (MIS-C) is a pathologic condition that has emerged during the coronavirus disease 2019 (COVID-19) pandemic. Although the epidemiological evidence of association between MIS-C and SARS-CoV-2 infection has been demonstrated, its pathogenic mechanism is still undefined. We describe the case of a 17-year old female, previously vaccinated against SARS-CoV-2, presenting with a history of asthenia, fever, cough, anorexia, abdominal pain, and vomiting. During the hospitalization, the patient developed bilateral conjunctivitis, hand vasculitis, cutaneous rash, and multiple pulmonary nodules, following by hepatitis and pancreatitis. As she reported a high-risk contact with a SARS-CoV-2 positive patient 10 days before admission, the epidemiological link and the clinical picture characterized by multi-system organ disfunction and inflammatory biomarkers increase led us to the diagnosis of MIS-C. Therefore, the patient was treated with intravenous immunoglobulin and corticosteroids, resulting in a rapid resolution of fever, cutaneous, and pulmonary involvement, while the recovery of hepatitis and pancreatitis was observed in the following weeks. This case leads to the discussion on whether SARS-CoV-2 immunized children and adolescents should be considered at risk of developing MIS-C and on their possible presentation with non-classic clinical features. Additionally, due to the increasing number of vaccinated children and adolescents, the issues resulting either from the diagnostic suspect of MIS-C or from the consequent need of an early therapeutic approach are discussed.

Central Precocious Puberty in Boys and Girls: Similarities and Differences

Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes.

Long COVID-19 in Children: From the Pathogenesis to the Biologically Plausible Roots of the Syndrome.

Long Coronavirus disease-19 (COVID-19) refers to the persistence of symptoms related to the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This condition is described as persistent and can manifest in various combinations of signs and symptoms, such as fatigue, headache, dyspnea, depression, cognitive impairment, and altered perception of smells and tastes. Long COVID-19 may be due to long-term damage to different organs-such as lung, brain, kidney, and heart-caused by persisting viral-induced inflammation, immune dysregulation, autoimmunity, diffuse endothelial damage, and micro thrombosis. In this review, we discuss the potential and biologically plausible role of some vitamins, essential elements, and functional foods based on the hypothesis that an individual's dietary status may play an important adjunctive role in protective immunity against COVID-19 and possibly against its long-term consequences.

Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study.

BACKGROUND: The long-term sequelae of coronavirus disease 2019 (COVID-19) in children remain poorly characterised. This study aimed to assess long-term outcomes in children previously hospitalised with COVID-19 and associated risk factors. METHODS: This is a prospective cohort study of children (≤18 years old) admitted to hospital with confirmed COVID-19. Children admitted between 2 April 2020 and 26 August 2020 were included. Telephone interviews used the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 Health and Wellbeing Follow-up Survey for Children. Persistent symptoms (>5 months) were further categorised by system(s) involved. RESULTS: 518 out of 853 (61%) eligible children were available for the follow-up assessment and included in the study. Median (interquartile range (IQR)) age was 10.4 (3-15.2) years and 270 (52.1%) were girls. Median (IQR) follow-up since hospital discharge was 256 (223-271) days. At the time of the follow-up interview 126 (24.3%) participants reported persistent symptoms, among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%) and sensory problems (29, 5.6%) were the most common. Multiple symptoms were experienced by 44 (8.4%) participants. Risk factors for persistent symptoms were: older age "6-11 years" (OR 2.74, 95% CI 1.37-5.75) and "12-18 years" (OR 2.68, 95% CI 1.41-5.4), and a history of allergic diseases (OR 1.67, 95% CI 1.04-2.67). CONCLUSIONS: A quarter of children experienced persistent symptoms months after hospitalisation with acute COVID-19 infection, with almost one in 10 experiencing multisystem involvement. Older age and allergic diseases were associated with higher risk of persistent symptoms at follow-up.

Uptake of Vaccinations among Children with Chronic Diseases Is Affected by Knowledge Gaps and Implementation Challenges in Italy.

(1) Background: Children with chronic medical conditions may be at increased risk for severe complications related to vaccine-preventable infections. Therefore, additional booster doses or supplementary vaccines are recommended, over and above the routine immunization schedule for healthy children. The aim of this study was to investigate attitude, knowledge, and practices toward additional vaccinations for children affected by chronic conditions among pediatricians and parents. (2) Methods: This study is based on two surveys: (i) a national cross-sectional survey, targeting pediatrician working in hospitals or in the primary health sector; (ii) a local cross-sectional survey, targeting parents of children with a previous diagnosis of chronic disease. (3) Results: Despite the fact that most of the health professionals and parents interviewed had an overall positive vaccine attitude, most pediatricians did not show an adequate knowledge of additional vaccinations for children affected by chronic diseases. Moreover, the coverage of additional recommended vaccinations in chronic pediatric patients was low. (4) Conclusions: This research highlighted important existing challenges hampering optimal vaccination coverage among pediatric chronic patients, including knowledge gaps on tailored vaccination schedules among pediatricians and organizational issues. The ongoing review of the Italian national immunization plan is a not-to-be-missed-opportunity to include evidence-based, detailed, and comprehensive recommendations on vaccinations for children affected by chronic conditions.

Chronic respiratory diseases other than asthma in children: the COVID-19 tsunami.

Coronavirus disease 2019 (COVID-19) affects all components of the respiratory system, including the neuromuscular breathing apparatus, conducting and respiratory airways, pulmonary vascular endothelium, and pulmonary blood flow. In contrast to other respiratory viruses, children have less severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A minority of children experience a post-infectious inflammatory syndrome, the pathology and long-term outcomes of which are poorly understood. The reason for the lower burden of symptomatic disease in children is not yet clear, but several pathophysiological characteristics are postulated. The SARS-CoV-2 pandemic has brought distinct challenges to the care of children globally. Proper recommendations have been proposed for a range of non-asthmatic respiratory disorders in children, including primary ciliary dyskinesia and cystic fibrosis. These recommendations involve the continuation of the treatment during this period and ways to maintain stability. School closures, loss of follow-up visit attendance, and loss of other protective systems for children are the indirect outcomes of measures to mitigate the COVID-19 pandemic. Moreover, COVID-19 has reshaped the delivery of respiratory care in children, with non-urgent and elective procedures being postponed, and distancing imperatives have led to rapid scaling of telemedicine. The pandemic has seen an unprecedented reorientation in clinical trial research towards COVID-19 and a disruption in other trials worldwide, which will have long-lasting effects on medical science. In this narrative review, we sought to outline the most recent findings on the direct and indirect effects of SARS-CoV-2 pandemic on pediatric respiratory chronic diseases other than asthma, by critically revising the most recent literature on the subject.

Probiotics as Adjuvants in Vaccine Strategy: Is There More Room for Improvement?

BACKGROUND: It has been recognized that microbiota plays a key role in shaping immune system maturation and activity. Since probiotic administration influences the microbiota composition and acts as a biological response modifier, the efficacy of an adjuvant for boosting vaccine-specific immunity is investigated. METHODS: A review of the literature was performed, starting from the mechanisms to laboratory and clinical evidence. RESULTS: The mechanisms, and in vitro and animal models provide biological plausibility for microbiota use. Probiotics have been investigated as adjuvants in farm conditions and as models to understand their potential in human vaccinations with promising results. In human studies, although probiotics were effective in ameliorating seroconversion to vaccines for influenza, rotavirus and other micro-organisms, the results for clinical use are still controversial, especially in particular settings, such as during the last trimester of pregnancy. CONCLUSION: Although this topic remains controversial, the use of probiotics as adjuvant factors in vaccination represents a strategic key for different applications. The available data are deeply influenced by heterogeneity among studies in terms of strains, timing and duration of administration, and patients. Although these do not allow us to draw definitive conclusions, probiotics as adjuvants in vaccination should be considered in future studies, especially in the elderly and in children, where vaccine effectiveness and duration of immunization really matter.

Asthma and COVID-19: a dangerous liaison?

The coronavirus disease 2019 (COVID-19) pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), provoked the most striking international public health crisis of our time. COVID-19 can cause a range of breathing problems, from mild to critical, with potential evolution to respiratory failure and acute respiratory distress syndrome. Elderly adults and those affected with chronic cardiovascular, metabolic, and respiratory conditions carry a higher risk of severe COVID-19. Given the global burden of asthma, there are well-founded concerns that the relationship between COVID-19 and asthma could represent a "dangerous liaison".Here we aim to review the latest evidence on the links between asthma and COVID-19 and provide reasoned answers to current concerns, such as the risk of developing SARS-CoV-2 infection and/or severe COVID-19 stratified by asthmatic patients, the contribution of type-2 vs. non-type-2 asthma and asthma-COPD overlap to the risk of COVID-19 development. We also address the potential role of both standard anti-inflammatory asthma therapies and new biological agents for severe asthma, such as mepolizumab, reslizumab, and benralizumab, on the susceptibility to SARS-CoV-2 infection and severe COVID-19 outcomes.

Management of patients with X-linked hypophosphatemic rickets during Covid-19 pandemic lockdown.

OBJECTIVES: To identify a safe pathway for management and treatment of patients with X-linked hypophosphatemic rickets (XLH) during Covid-19 pandemic lockdown. METHODS: Twenty-six patients with XLH (age 3.1-25.7 years) were enrolled in Pediatric Endocrine Unit; nine of them were receiving human monoclonal anti-fibroblast growth factor 23 antibody (burosumab) and 17 (pediatric patients, age 9.5-17.9 years, n=7; young-adult patients, age 20.1-25.7 years, n=10) received conventional treatment with inorganic oral phosphate salts and active vitamin D metabolites. A Covid-19 free pathway was addressed for XLH patients receiving burosumab treatment in hospital. XLH patients receiving conventional treatment were followed by phone calls, e-mails, or telemedicine. RESULTS: All XLH patients receiving burosumab continued the scheduled follow-up and treatment; none of them was infected by Covid-19. Seven XLH patients out of 17 (41%) receiving conventional treatment showed some complication related to the disease itself or its treatment: periapical abscess with gingival fistula was diagnosed in five patients (three children and two young-adults) and treated with antibiotics with complete resolution; one child showed abdominal pain due to the administration of high doses of inorganic oral phosphate salts solved by reducing the dosage, and one child had severe legs pain during deambulation after orthopedic surgery solved with common analgesics. CONCLUSIONS: Covid-19 free pathway was safe and effective to manage XLH patients receiving burosumab. E-health technologies were useful methods to follow XLH patients receiving conventional treatment during Covid-19 pandemic lockdown.

Could nutritional supplements act as therapeutic adjuvants in COVID-19?

BACKGROUND: The role of the immune system and inflammatory response in the pathogenesis of the severe manifestations of coronavirus disease 2019 (COVID-19) is well known. Currently, different therapies active on the immune system are used for the management of COVID-19. The involvement of the immune system also opens the opportunity for the use of nutritional supplements with antimicrobial and immunomodulatory activity. MAIN ASPECTS: Nutritional supplements with antimicrobial and immunomodulatory activity are promising therapeutic adjuvants for the treatment of COVID-19, and also for the prevention of viral spreading. In particular, the role of vitamin D, probiotics, lactoferrin, and zinc is of significant clinical interest, although there are only a few data on their use in COVID-19 patients. Their molecular actions, together with the results of studies performed on other respiratory infections, strongly suggest their potential utility in COVID-19. This article discusses the main properties of these nutritional supplements and their potential applicability in the prevention and treatment of COVID-19. CONCLUSION: The supplementation with vitamin D, probiotics, lactoferrin and zinc could have a role both in preventing SARS-CoV-2 infection and in mitigating the clinical course in infected patients, contributing in the prevention of immune-mediated organ damage.

PTSD in parents of children with severe diseases: a systematic review to face Covid-19 impact.

CONTEXT: The literature agrees on the impact of post-traumatic stress symptoms in parents of seriously ill children but there is less clarity about the real extent and gender differences of this psychopathological risk. The recent Covid-19 outbreak highlighted new burdens for researchers on Post Traumatic Stress Disorder (PTSD) and clear evidence-based knowledge on this issue is timely needed. OBJECTIVE: In this review, we present a synthesis of the updated evidence on PTSD rates in parents of children with severe diseases. We also aim to try to understand if research in this field has been refined over time with the long-term intent to better face the new challenges of Covid-19 in the paediatric field. DATA SOURCES: The PubMed database was searched. STUDY SELECTION: Studies were included if they assessed PTSD in parents of children diagnosed with physical illnesses. DATA EXTRACTION: Of 240 studies, 4 were included. RESULTS: Analysis of the 4 studies revealed 2 studies with PTSD rates around 20% and in line with previous best-evidence. All 4 studies tried to provide more data on fathers, however, all the studies present the lack of a control group. LIMITATIONS: The limited number of studies, which also differ widely in the methodology used. CONCLUSIONS: Methodological errors evidenced in all the 4 studies limit their reliability, making the understanding of the paediatric caregiver's concern regarding PTSD still difficult. More sound research is needed.

Challenges and management of neurological and psychiatric manifestations in SARS-CoV-2 (COVID-19) patients.

COVID-19 is a pandemic caused by human coronavirus (HCoV) SARS-CoV-2, which originated in Wuhan, China, at the end of 2019 and spread globally during 2020. Due to the difficulty of clinical decision-making during this period, our study group reviewed current literature focusing on the neurological and psychiatric aspects of COVID-19. Despite the knowledge on this newly discovered virus which is constantly evolving, different pieces of evidence reported an association between COVID-19 and neurological symptoms like headache, dizziness, taste and smell disorders and complications involving the nervous system eventually triggered by the pathologic processes elicited by SARS-CoV-2. It seems that younger patients are less prone to develop severe forms of COVID-19. However, neurological signs have been reported in paediatric patients as well, and in some cases, the infection presented neurological sequelae. Furthermore, children with particular neurological diseases or treated with specific drugs (e.g. immune-suppressant therapies) must be carefully monitored during this pandemic. Neurologists should be aware of the main drug-drug interactions and the neurological side effects of COVID-19 treatments. Notably, adverse mental health impact has been reported in patients with SARS-CoV-2, which could be related either to the social strain or to the eventual neurotropic effects of the virus, which in other infections have been proven to promote the onset of psychiatric symptoms. Further, psychiatric population may be more vulnerable to the infection and at higher risk for adverse outcomes.

Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic.

The COVID-19 pandemic has surprised the entire population. The world has had to face an unprecedented pandemic. Only, Spanish flu had similar disastrous consequences. As a result, drastic measures (lockdown) have been adopted worldwide. Healthcare service has been overwhelmed by the extraordinary influx of patients, often requiring high intensity of care. Mortality has been associated with severe comorbidities, including chronic diseases. Patients with frailty were, therefore, the victim of the SARS-COV-2 infection. Allergy and asthma are the most prevalent chronic disorders in children and adolescents, so they need careful attention and, if necessary, an adaptation of their regular treatment plans. Fortunately, at present, young people are less suffering from COVID-19, both as incidence and severity. However, any age, including infancy, could be affected by the pandemic.Based on this background, the Italian Society of Pediatric Allergy and Immunology has felt it necessary to provide a Consensus Statement. This expert panel consensus document offers a rationale to help guide decision-making in the management of children and adolescents with allergic or immunologic diseases.