Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

High Cardiac Troponin Levels in Infants with Acute SARS-CoV-2 Infection: A Prospective Comparative Study.

OBJECTIVE: To investigate the specific role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in inducing elevation of marker of myocardial injury in infants with acute coronavirus disease 2019 (COVID-19). STUDY DESIGN: A prospective, multicentric 3-arm comparative study (March 2020 through March 2022) enrolling 152 infants hospitalized for COVID-19, 79 children with acute infections other than SARS-CoV-2, and 71 healthy controls. Determination of high-sensitivity cardiac troponin (hs-cTn) levels was the primary outcome. RESULTS: The proportion of children with hs-cTn values above the upper limit of normal (44 [28.9%]), as well as with a 3-fold increased value (20 [13.2%]) were significantly higher in the COVID-19 group than those in both control groups. The risk of presenting a 3-fold increased hs-cTn value was higher in children with SARS-CoV-2 infection compared with either healthy children (OR, 5.23; 95% CI, 1.19-23.02) or those with other infections (OR, 11.89; 95% CI, 1.56-89.79). In children with COVID-19, hs-cTn elevation was associated with neither clinical nor biochemical characteristics, nor perinatal risk factors, but with an age of <3 months (P < .001). After adjustment for age, sex, and underlying clinical conditions, elevated hs-cTn was independently associated with COVID-19 in a multivariable regression model. All children showed a progressive reduction of hs-cTn until normalization over time, without clinical, ECG, or echocardiographic manifestations up to 1 year of follow-up. CONCLUSIONS: Infants with acute SARS-CoV-2 infection may show a subclinical and transient alteration of myocardial injury markers, especially in the first months of life. hs-cTn levels normalized during follow-up and were not associated with cardiac functional impairment; nevertheless, long-term consequences are unknown and should be followed carefully.

The diagnostic and therapeutic challenge of atrial flutter in children: a case report.

BACKGROUND: Palpitations represent a common cause for consultation in the pediatric Emergency Department (ED). Unlike adults, palpitations in children are less frequently dependent from the heart, recognizing other causes. CASE PRESENTATION: A 11-year-old male came to our pediatric ED for epigastric pain, vomiting and palpitations. During the previous 6 month the patient was affected by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus). Electrocardiogram (ECG) revealed supraventricular tachycardia. Therefore, adenosine was administered unsuccessfully. The administration of adenosine, however, allowed us to make diagnosis of atypical atrial flutter. Multiple attempts at both electrical cardioversion, transesophageal atrial overdrive, and drug monotherapy were unsuccessful in our patient. Consequently, a triple therapy with amiodarone, flecainide, and beta-blocker was gradually designed to control the arrhythmic pattern with the restoration of a left upper atrial rhythm. There was not any evidence of sinus rhythm in the patient clinical history. CONCLUSIONS: The present study underlines the rarity of this type of dysrhythmia in childhood and the difficulties in diagnosis and management, above all in a patient who has never showed sinus rhythm. Raising awareness of all available treatment options is essential for a better management of dysrhythmia in children.

Incomplete Kawasaki Disease with Peripheral Facial Nerve Palsy and Lung Nodules: A Case Report and Literature Review.

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher incidence of coronary arteries lesions and may be an indicator of a more severe disease. Here, we describe a case of lower motor neuron facial nerve palsy complicating KD and perform an extensive literature review to better characterize clinical features and treatment of patients with KD-associated facial nerve palsy. The patient was diagnosed at the sixth day of disease and presented extensive coronary artery lesions. A prompt treatment with intravenous immunoglobulins, aspirin and steroids obtained a good clinical and laboratory response, with resolution of facial nerve palsy and improvement of coronary lesions. The incidence of facial nerve palsy is 0.9-1.3%; it is often unilateral, transient, more frequent on the left and seemingly associated with coronary impairment. Our literature review showed coronary artery involvement in the majority of reported cases (27/35, 77%) of KD with facial nerve palsy. Unexplained facial nerve palsy in young children with a prolonged febrile illness should prompt consideration of echocardiography to exclude KD and start the appropriate treatment.

SARS-CoV-2-related bronchiolitis: a multicentre international study.

BACKGROUND: Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited. OBJECTIVE: To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses. SETTING, PATIENTS, INTERVENTIONS: A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected. MAIN OUTCOME MEASURES: The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative. RESULTS: 2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85). CONCLUSIONS: SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.

Seizures in Children with SARS-CoV-2 Infection: Epidemiological, Clinical and Neurophysiological Characterization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide variety of symptoms, including neurological manifestations. We investigated clinical, demographic, laboratory, neurophysiological and imaging characteristics of SARS-CoV-2-positive children with seizures and analyzed differences between children admitted during the periods with prevalent circulation of the Alpha/Delta and Omicron variants, respectively. Patients' characteristics were analyzed according to the presence or absence of seizures and then according to the SARS-CoV-2 variants. Five-hundred and four SARS-CoV-2-positive patients were included: 93 (18.4%) with seizures and 411 (81.6%) without. Patients with seizures were older, had more commonly an underlying epilepsy and had more frequently altered C-reactive protein than those without seizures. Electroencephalography was abnormal in 5/38 cases. According to the SARS-CoV-2 variant, seizures were recorded in 4.7% of the total number of hospitalized patients during the Alpha/Delta period, and in 16.9% of patients admitted during the Omicron period. During the Alpha/Delta variants, seizures were more commonly observed in patients with epilepsy compared to those observed during the Omicron period. Our findings suggest that although SARS-CoV-2 may potentially trigger seizures, they are generally not severe and do not require intensive care admission.

MIS-C: A COVID-19-as sociated condition between hypoimmunity and hyperimmunity.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of COVID-19. A better knowledge of immunological, cellular, and genetic characteristics of MIS-C could help better understand the pathogenesis of the disease and contribute to identifying specific diagnostic biomarkers and develop targeted therapies. We studied 37 MIS-C children at hospital admission and 24 healthy controls analyzing serum cytokines (IFN-α, IFN-ß, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70 and TNF), lymphocyte populations by flow cytometry and 386 genes related to autoimmune diseases, autoinflammation and primary immunodeficiencies by NGS. MIS-C patients showed a significant increase of serum IFNγ (despite a significant reduction of activated Th1) and ILs, even if with a great heterogeneity among patients, revealing different pathways involved in MIS-C pathogenesis and suggesting that serum cytokines at admission may help to select the inflammatory pathways to target in each patient. Flow cytometry demonstrated a relevant reduction of T populations while the percentage of B cell was increased in agreement with an autoimmune pathogenesis of MIS-C. Genetic analysis identified variants in 34 genes and 83.3% of patients had at least one gene variant. Among these, 9 were mutated in more patients. Most genes are related to autoimmune diseases like ATM, NCF1, MCM4, FCN3, and DOCK8 or to autoinflammatory diseases associated to the release of IFNγ like PRF1, NOD2, and MEF. Thus, an incomplete clearance of the Sars-CoV2 during the acute phase may induce tissue damage and self-antigen exposure and genetic variants can predispose to hyper-reactive immune dysregulation events of MIS-C-syndrome. Type II IFN activation and cytokine responses (mainly IL-6 and IL-10) may cause a cytokine storm in some patients with a more severe acute phase of the disease, lymphopenia and multisystemic organ involvement. The timely identification of such patients with an immunocytometric panel might be critical for targeted therapeutic management.

Immunophenotyping of peripheral blood cells allows to discriminate MIS-C and Kawasaki disease.

Background: The pathogenesis of the novel described multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) is still debated as it is not clear if they are the same or different nosological entities. However, for both the diseases a rapid and unequivocal diagnosis is mandatory to start the therapy before the onset of severe complications. In this study, we aimed to evaluate the white cell populations in MIS-C and KD as potential markers to discriminate between the two diseases. Methods: We studied white cell populations by flow cytometry in 46 MIS-C and 28 KD patients in comparison to 70 age-matched healthy children. Results: MIS-C patients had a significant lymphopenia that involved both B and T populations while KD patients showed a significant neutrophilia and thrombocythemia. Granulocyte/lymphocyte ratio helped to diagnose both MIS-C and KD with a high diagnostic sensitivity, while a multivariate analysis of granulocyte and T lymphocyte number contributed to discriminate between the two diseases. Conclusions: The relevant lymphopenia observed in MIS-C patients suggests that the disease would be a post-infectious sequel of COVID-19 immunologically amplified by a massive cytokine release, while the significant neutrophilia and thrombocythemia observed in KD confirmed that the disorder has the genesis of a systemic vasculitis. The analysis of a panel of circulating cells may help to early diagnose and to discriminate between the two diseases. Supplementary Information: The online version contains supplementary material available at 10.1186/s41231-022-00128-2.

Changing Epidemiology of Acute Viral Respiratory Infections in Hospitalized Children: The Post-Lockdown Effect.

Several reports highlighted how public health measures aimed at limiting severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) circulation have likely contributed to reducing the circulation of other respiratory viruses, particularly during the first year of the COVID-19 pandemic. We evaluated the epidemiology of acute respiratory infections in a large cohort of hospitalized children during the third year of the pandemic (2021−2022). We retrospectively analyzed data from the health records of children (<14 years) hospitalized for acute respiratory infections between 1 July 2021 and 31 March 2022. A total of 1763 respiratory panels were collected. Overall, 1269 (72%) panels hadpositive results for at least one pathogen. Most positive panels (53.8%) belonged to patients aged 1−12 months. The most detected pathogen was respiratory syncytial virus (RSV) (57.8% of positive panels). The RSV peak occurred in November 2021. Nine hundred and forty-five (74.5%) panels were positive for one pathogen while three hundred and twenty-four (25.5%) showed multiple infections. Patients with multiple infections were significantly older than those with a single infection. The 2021−2022 peak of RSV infection in Italy occurred earlier than in the previous pre-pandemic seasons. A high number of children have been hospitalized because of acute viral infections also due to less aggressive viruses.

Biomarkers of Endothelial Damage in Distinct Phases of Multisystem Inflammatory Syndrome in Children.

Endothelial hyperinflammation and vasculitis are known hallmarks of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C). They are due to the direct effect of the virus on endothelial cells enhanced by pro-inflammatory modulators and may cause venous/arterial thrombosis. Therefore, it is essential to identify patients with endothelial damage early in order to establish specific therapies. We studied the monocyte chemoattractant protein 1 (MCP-1), the perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), and the vascular endothelial growth factor A (VEGF-A) in serum from 45 MIS-C patients at hospital admission and 24 healthy controls (HC). For 13/45 MIS-C patients, we measured the three serum biomarkers also after one week from hospitalization. At admission, MIS-C patients had significantly higher levels of MCP-1 and VEGF-A than the HC, but no significant differences were observed for pANCA. While after one week, MCP-1 was significantly lower, pANCA was higher and VEGF-A levels were not significantly different from the admission values. These findings suggest an involvement of epithelium in MIS-C with an acute phase, showing high MCP-1 and VEGF-A, followed by an increase in pANCA that suggests a vasculitis development. The serum biomarker levels may help to drive personalized therapies in these phases with anticoagulant prophylaxis, immunomodulators, and/or anti-angiogenic drugs.

Distinctive Phenotype of Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 According to Patients' Age: A Monocentric Experience.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a disease temporally related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is characterized by fever, conjunctival injections, rash, gastrointestinal symptoms, and cardiovascular complications. We evaluated the clinical presentation, laboratory findings, imaging features, therapeutic interventions, and hospital course of a monocentric cohort, and we analyzed these findings according to two age groups. Methods: Patients with MIS-C admitted to a Tertiary Care Pediatric Hospital from November 2020 to November 2021 were considered for the enrollment. Results: Overall, 35 consecutive patients were included. Most of the children did not require intensive care unit at the admission. The clinical presentation of MIS-C slightly differs according to age groups. Mucocutaneus involvement was more frequent in younger patients, while abdominal symptoms were present in 54% of patients aged less than 5 years and in 95% of patients aged more than 5 years (p < 0.05). In addition, the number of cases with troponin above the normal reference value was significantly higher in older patients (77%) compared to younger cases (15%) (p < 0.01). Conclusions: MIS-C is a new emerging condition and represents a challenge to pediatricians due to the severity of presentation. Further studies to better characterize the long-term outcome of MIS-C patients are mandatory.

Liver and Pancreatic Involvement in Children with Multisystem Inflammatory Syndrome Related to SARS-CoV-2: A Monocentric Study.

Liver and pancreatic involvement in children with Multisystem Inflammatory Syndrome related to SARS-CoV-2 (MIS-C) has been poorly investigated so far. We reviewed a cohort of MIS-C patients to analyze the prevalence of acute liver injury (ALI) and pancreatic injury and their correlation with clinical outcomes. Demographic, clinical, laboratory and imaging features of children with MIS-C at admission and during hospital stay were prospectively collected. Fifty-five patients (mean age 6.5 ± 3.7 years) were included. At admission, 16 patients showed ALI and 5 had increased total serum lipase. During observation, 10 more patients developed ALI and 19 more subjects presented raised pancreatic enzymes. In comparison to those with normal ALT, subjects with ALI were significantly older (p = 0.0004), whereas pancreatic involvement was associated to a longer duration of hospital stay compared with patients with normal pancreatic enzymes (p = 0.004). Time between hospital admission and onset of ALI was shorter compared to the onset of raised pancreatic enzymes (3.2 ± 3.9 versus 5.3 ± 2.7 days, respectively; p = 0.035). Abdominal ultrasound showed liver steatosis in 3/26 (12%) and hepatomegaly in 6/26 (16%) patients with ALI; 2 patients presented enlarged pancreas. Although liver and pancreatic involvement is commonly observed in MIS-C patients, it is mild in most cases with a complete recovery.

Brugada Pattern in a Child with Severe SARS-CoV-2 Related Multisystem Inflammatory Syndrome.

This report presents the first case of Brugada pattern complicated by a supraventricular arrhythmia in a child with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C). A 7-year-old boy came to our Emergency Department with 7 days of abdominal pain and fever. MIS-C was diagnosed on the basis of the clinical, laboratory and instrumental tests. On admission, ECG showed type 1 Brugada pattern in the right precordial leads. During hospitalization the onset of supraventricular arrhythmias complicated the clinical picture. This case underlines management complexity of supraventricular arrhythmic events, different from atrial fibrillation, in patients with Brugada pattern in the context of a systemic inflammatory condition with significant cardiac involvement. All potential therapeutic choices should be considered to ensure the best outcomes.

Italian consensus on the therapeutic management of uncomplicated acute hematogenous osteomyelitis in children.

BACKGROUND: Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient's age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. METHODS: A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. RESULTS: Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. CONCLUSIONS: The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.