SARS-CoV-2 infection in children: A 24 months experience with focus on risk factors in a pediatric tertiary care hospital in Milan, Italy.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is characterized by a wide variety of expressions ranging from asymptomatic to, rarely, critical illness. The basis of this variability is not yet fully understood. The aim of this study was to identify clinical and genetic risk factors predisposing to disease susceptibility and progression in children. Methods: We enrolled 181 consecutive children aged less than 18 years hospitalized with or for SARS-CoV-2 infection during a period of 24 months. Demographic, clinical, laboratory, and microbiological data were collected. The development of coronavirus disease 2019 (COVID-19)-related complications and their specific therapies were assessed. In a subset of 79 children, a genetic analysis was carried out to evaluate the role of common COVID-19 genetic risk factors (chromosome 3 cluster; ABO-blood group system; FUT2, IFNAR2, OAS1/2/3, and DPP9 loci). Results: The mean age of hospitalized children was 5.7 years, 30.9% of them being under 1 year of age. The majority of children (63%) were hospitalized for reasons different than COVID-19 and incidentally tested positive for SARS-CoV-2, while 37% were admitted for SARS-CoV-2 infection. Chronic underlying diseases were reported in 29.8% of children. The majority of children were asymptomatic or mildly symptomatic; only 12.7% developed a moderate to critical disease. A concomitant pathogen, mainly respiratory viruses, was isolated in 53.3%. Complications were reported in 7% of children admitted for other reasons and in 28.3% of those hospitalized for COVID-19. The respiratory system was most frequently involved, and the C-reactive protein was the laboratory test most related to the development of critical clinical complications. The main risk factors for complication development were prematurity [relative risk (RR) 3.8, 95% confidence interval (CI) 2.4-6.1], comorbidities (RR 4.5, 95% CI 3.3-5.6), and the presence of coinfections (RR 2.5, 95% CI 1.1-5.75). The OAS1/2/3 risk variant was the main genetic risk factor for pneumonia development [Odds ratio (OR) 3.28, 95% CI 1-10.7; p value 0.049]. Conclusion: Our study confirmed that COVID-19 is generally less severe in children, although complications can develop, especially in those with comorbidities (chronic diseases or prematurity) and coinfections. Variation at the OAS1/2/3 genes cluster is the main genetic risk factor predisposing to COVID-19 pneumonia in children.

Meningococcal Disease in Pediatric Age: A Focus on Epidemiology and Prevention.

Meningococcal disease is caused by Neisseria meningitidis; 13 serogroups have been identified and differentiated from each other through their capsular polysaccharide. Serotypes A, B, C, W, X, and Y are responsible for nearly all infections worldwide. The most common clinical manifestations are meningitis and invasive meningococcal disease, both characterized by high mortality and long-term sequelae. The infection rate is higher in children younger than 1 year and in adolescents, who are frequently asymptomatic carriers. Vaccination is the most effective method of preventing infection and transmission. Currently, both monovalent meningococcal vaccines (against A, B, and C serotypes) and quadrivalent meningococcal vaccines (against serogroups ACYW) are available and recommended according to local epidemiology. The purpose of this article is to describe the meningococcal vaccines and to identify instruments that are useful for reducing transmission and implementing the vaccination coverage. This aim could be reached by switching from the monovalent to the quadrivalent vaccine in the first year of life, increasing vaccine promotion against ACYW serotypes among adolescents, and extending the free offer of the anti-meningococcal B vaccine to teens, co-administering it with others proposed in the same age group. Greater awareness of the severity of the disease and increased health education through web and social networks could represent the best strategies for promoting adhesion and active participation in the vaccination campaign. Finally, the development of a licensed universal meningococcal vaccine should be another important objective.

Incidental occurrence of neutropenia in children hospitalised for COVID-19.

BACKGROUND: Investigations on haematological alterations in paediatric COVID-19 have been focused mostly on lymphocytes and clotting profiles. Neutropenia has been occasionally reported and its course and impact on the disease have not been elucidated. The aim of this study was to describe the epidemiology, course, and impact of neutropenia in children with COVID-19 hospitalised in a tertiary care referral paediatric ward. METHODS: A single-centre retrospective study was conducted. Hospitalised children between 1 month and 18 years with confirmed COVID-19 and neutropenia were included and compared to non neutropenic patients. Complete blood picture with differential blood count, serum biochemistry, clotting profiles were performed; clinical data, length of hospitalisation, and prescription of drugs were collected. RESULTS: Twelve out of 95 patients (12.63%) with documented SARS-CoV-2 infection were neutropenic and met the inclusion criteria. The mean age was 161 days (range 38-490 days). The mean duration of symptoms in neutropenic children was 3.82 days, while the mean length of hospitalisation was 7.67 days. These findings were not significantly different in the two study groups. All patients had mild clinical manifestations and were discharged without sequelae. CONCLUSIONS: We provided the first comprehensive study on neutropenia in mild paediatric COVID-19 infection. Our findings show that the main features of this haematological disorder in COVID-19 are analogous to the well-known transient benign neutropenia associated with other common viral infections. In our setting, neutropenia does not emerge as a potential negative prognostic factor in paediatric COVID-19.

Panton-valentine leukocidin Staphylococcus aureus severe infection in an infant: a case report and a review of the literature.

BACKGROUND: Panton-Valentine leukocidin (PVL) is one of the major virulence factor of Staphylococcus aureus (SA) that might be associated with invasive life-threating infections. A prompt diagnosis and adequate treatment are essential in achieving the best outcome and avoiding serious sequelae. We describe a case of severe invasive PVL-SA infection in an infant. A literature review starting from 2010 was also performed in order to discuss clinical presentations, radiological findings, treatment and outcome. CASE PRESENTATION: This is a case of a 6-month-old boy who rapidly developed high fever and poor general condition. He was diagnosed as having multiple muscular abscesses, multiple foci of osteomyelitis and bloodstream infections caused by Panton-Valentine leukocidin Methicillin-resistant Staphylococcus aureus. He received intravenous antibiotics and surgical drainage of the abscess with progressive recovery. CONCLUSION: Our report highlights the importance of improving awareness of this severe infection, as a prompt diagnosis and adequate manage is essential in order to save life and to prevent serious complications.

Pediatric Septic Arthritis of the Knee Due to a Multi-Sensitive Streptococcus pyogenes Strain Responsive to Clindamycin-A Case Report.

Septic arthritis is an inflammatory process usually generated by a bacterial infection. The knee is one of the most frequently involved joints. The etiology varies depending on age, and hematogenous spread remains the primary cause in children. Herein, we report a case of a previously healthy three-year-old female who was referred to our institution for acute swelling of her right knee. After a clinical and radiological diagnosis of septic arthritis, an empirical treatment with a combination of cefotaxime and clindamycin was initiated. The isolation of a multi-sensitive Streptococcus pyogenes strain from the joint's effusion prompted the discontinuation of clindamycin and the usage of cefotaxime alone. One week later, an ultrasound was executed due to worsening in the patient's clinical conditions, and an organized corpuscular intra-articular effusion with diffuse synovial thickening was revealed. Cefotaxime was therefore replaced with clindamycin, which improved the symptoms. Despite the antibiotic sensitivity test having revealed a microorganism with sensitivity to both cephalosporin and clindamycin, clinical resistance to cefotaxime was encountered and a shift in the antimicrobial treatment was necessary to ensure a full recovery. This case study confirms that an antibiotic regimen based solely on a susceptibility test may be ineffective for such cases.

Diagnosis of SARS-CoV-2 in children: accuracy of nasopharyngeal swab compared to nasopharyngeal aspirate.

The tests currently used for the identification of SARS-CoV-2 include specimens taken from the upper and lower respiratory tract. Although recommendations from the World Health Organization prioritise the usage of a nasopharyngeal swab (NS), nasopharyngeal aspirates (NPA) are thought to be superior in identifying SARS-CoV-2 in children. To our knowledge, however, no paediatric study has been published on the subject. The aim of this study is to evaluate the diagnostic performances of NS referred to NPA for SARS-CoV-2 in children. We calculated the sensitivity and specificity of the NS referred to the NPA of the whole sample and considered both age and collection period as covariates in different analyses. We collected 300 paired samples. The NS had a specificity of 97.7% and a sensitivity of 58.1%. We found similar results for the group of subjects ≥ 6 years old, while for subjects < 6 years old, the sensitivity was 66.7% and the specificity 97.8%. Considering period as a covariate, the sensitivity and specificity for patients hospitalised in March (31 patients, 52 records) were 70.0% and 97.6%, while for patients involved in the follow-up (16 patients, 57 records), they were 57.2% and 89.7%. The NS has a low sensitivity in detecting SARS-CoV-2 in children when referred to the NPA, whereas its specificity is high. Our results suggest that in children under 6 years of age, NSs should be preferred whenever possible. Though statistically not significant, the sensitivity of the NS rises when performed before the NPA.

Pediatric otogenic cerebral venous sinus thrombosis: a case report and a literature review.

BACKGROUND: Cerebral venous sinus thrombosis in children is a rare but potentially fatal complication of acute mastoiditis, one of the most common pediatric infectious diseases. Due to its subtle clinical presentation, suspicion is essential for a prompt diagnosis and appropriate management. Unfortunately, no standard treatment options are available. To discuss the possible clinical presentation, microbiology, and management, we here report the case of a child with otogenic cerebral venous sinus thrombosis and perform a literature review starting from 2011. CASE PRESENTATION: The child, a 10-months-old male, presented clinical signs of right acute otitis media and mastoiditis. Brain computed tomography scan detected right sigmoid and transverse sinus thrombosis, as well as a subperiosteal abscess. Fusobacterium necrophorum and Haemophilus Influentiae were detected on cultural sampling. A multidisciplinary approach along with a combination of medical and surgical therapy allowed the patient's full recovery. CONCLUSION: Cerebral venous sinus thrombosis is a rare but severe complication of acute otitis media and mastoiditis. The management of this pathological condition is always challenging and an interdisciplinary approach is frequently required. Current therapeutic options include a combination of medical and surgical therapy. A patient-centered approach should guide timing and treatment management.

Abscess of the clivus in an adolescent with complicated acute rhinosinusitis: a case report.

BACKGROUND: Complications of acute sinusitis affecting multiple sites are very uncommon, and generally develop for a delayed diagnosis of the primary infection, with possible severe and life-threatening evolution. Patients can have variable presentations according to the site and extent of the infection. Multiple forms generally include the coexistence of orbital manifestations and intracranial infections. We here present a case with unusual multiple sites locations (i.e.: intraorbital intraconic abscess, sigmoid sinus thrombosis, preclival abscess, multiple splanchnocranium osteomyelitic processes). CASE PRESENTATION: A 13-year-old male presented at our hospital with right progressive orbital oedema with eyesight worsening and signs of meningitis. Computed tomography and magnetic resonance (MRI) demonstrated right intraorbital intraconic abscess, left sphenoidal sinusitis, transverse and sigmoid sinus thrombosis. Ophthalmologic evaluation documented a right optic nerve sufferance. Endoscopic and superior right trans-palpebral surgical decompression was performed, and the abscess was drained. Microbiological analysis revealed the presence of multi-sensitive Streptococcus Intermedius. Subsequent prolonged antibiotic and anti-thrombotic treatments were started. In the following two-weeks the sinusal and ophthalmologic clinical conditions improved, whereas the patients complained of mild to moderate cervical pain and suffered from intermittent pyrexia. Control MRI documented clival abscess extending up to preclival soft tissues posterior to the nasopharynx, associated with mandible osteomyelitis, occipital condyles and anterior part of the temporal bone hyper intensity. Endoscopic trans-nasal surgical approach to the clival compartment with neurosurgery navigation-guided achieved preclival abscess drainage. Complete clinical and radiological recovery was achieved after 45 days of medical treatment. CONCLUSIONS: Multiple sites complicated rhinosinusitis is uncommon, and its management is challenging. A proper history and thorough clinical examination along with a radiological evaluation are key factors in the final diagnosis of patients with complicated multiple sites acute rhinosinusitis. A quick multidisciplinary approach is always necessary to avoid unwanted life-threatening complications.

Henoch-Schönlein Purpura in children: not only kidney but also lung.

BACKGROUND: Henoch-Schönlein Purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels. Pulmonary involvement is a rare complication of HSP and diffuse alveolar hemorrhage (DAH) is the most frequent clinical presentation. Little is known about the real incidence of lung involvement during HSP in the pediatric age and about its diagnosis, management and outcome. METHODS: In order to discuss the main clinical findings and the diagnosis and management of lung involvement in children with HSP, we performed a review of the literature of the last 40 years. RESULTS: We identified 23 pediatric cases of HSP with lung involvement. DAH was the most frequent clinical presentation of the disease. Although it can be identified by chest x-ray (CXR), bronchoalveolar lavage (BAL) is the gold standard for diagnosis. Pulse methylprednisolone is the first-line of therapy in children with DAH. An immunosuppressive regimen consisting of cyclophosphamide or azathioprine plus corticosteroids is required when respiratory failure occurs. Four of the twenty-three patients died, while 18 children had a resolution of the pulmonary involvement. CONCLUSIONS: DAH is a life-threatening complication of HSP. Prompt diagnosis and adequate treatment are essential in order to achieve the best outcome.

Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract development, leading to a severe, lifelong disease. In this review, what is presently known regarding BPD pathogenesis, its impact on long-term pulmonary morbidity and mortality and the available preventive and therapeutic strategies are discussed. MAIN BODY: Bronchopulmonary dysplasia is associated with persistent lung impairment later in life, significantly impacting health services because subjects with BPD have, in most cases, frequent respiratory diseases and reductions in quality of life and life expectancy. Prematurity per se is associated with an increased risk of long-term lung problems. However, in children with BPD, impairment of pulmonary structures and function is even greater, although the characterization of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment. Prenatal and postnatal preventive measures are extremely important to reduce the risk of BPD. CONCLUSION: Bronchopulmonary dysplasia is a respiratory condition that presently occurs in preterm neonates and can lead to chronic respiratory problems. Although knowledge about BPD pathogenesis has significantly increased in recent years, not all of the mechanisms that lead to lung damage are completely understood, which explains why therapeutic approaches that are theoretically effective have been only partly satisfactory or useless and, in some cases, potentially negative. However, prevention of prematurity, systematic use of nonaggressive ventilator measures, avoiding supraphysiologic oxygen exposure and administration of surfactant, caffeine and vitamin A can significantly reduce the risk of BPD development. Cell therapy is the most fascinating new measure to address the lung damage due to BPD. It is desirable that ongoing studies yield positive results to definitively solve a major clinical, social and economic problem.

A spectrum of inflammation and demyelination in acute disseminated encephalomyelitis (ADEM) of children.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that involves multifocal areas of the white matter, rarely the gray matter and spinal cord, mainly affecting children and mostly occurring 1-2weeks after infections or more rarely after vaccinations. Though a specific etiologic agent is not constantly identified, to evaluate carefully patient's clinical history and obtain adequate samples for the search of a potential ADEM causal agent is crucial. In the case of a prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with full recovery, but in the case of diagnostic delays or inappropriate treatment some patients might display neurological sequelae and persistent deficits or even show an evolution to multiple sclerosis. The suspicion of ADEM rises on a clinical basis and derives from systemic and neurologic signs combined with magnetic resonance imaging of the central nervous system. Other advanced imaging techniques may help an appropriate differential diagnosis and definition of exact disease extension. Although there is no standardized protocol or management for ADEM, corticosteroids, intravenous immunoglobulin, and plasmapheresis have been successfully used. There is no marker that permits to identify the subset of children with worse prognosis and future studies should try to detect any biological clue for prevision of neurologic damage as well as should optimize treatment strategies using an approach based on the effective risk of negative evolution.