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.

Clinical Presentation and Severity of SARS-CoV-2 Infection Compared to Respiratory Syncytial Virus and Other Viral Respiratory Infections in Children Less than Two Years of Age.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the implementation of restrictive measures led to a dramatic reduction in respiratory syncytial virus (RSV) occurrence together with rare and mild bronchiolitis induced by SARS-CoV-2. We described the respiratory picture of SARS-CoV-2 infection and evaluated the frequency and the severity of SARS-CoV-2 bronchiolitis comparing it with other respiratory viral infections in children less than two years of age. The severity of respiratory involvement was evaluated based on the need for oxygen therapy, intravenous hydration, and the length of hospital stay. A total of 138 children hospitalized for respiratory symptoms were enrolled: 60 with SARS-CoV-2 and 78 with RSV. In the group of SARS-CoV-2-infected children, 13/60 (21%) received a diagnosis of co-infection. Among the enrolled children, 87/138 (63%) received a diagnosis of bronchiolitis. The comparative evaluation showed a higher risk of the need for oxygen therapy and intravenous hydration in children with RSV infection and co-infection compared to children with SARS-CoV-2 infection. In the children with a diagnosis of bronchiolitis, no differences in the main outcomes among the groups were observed. Although children with SARS-CoV-2 infection have less severe respiratory effects than adults, the pediatrician should pay attention to bronchiolitis due to SARS-CoV-2, which could have a severe clinical course in younger children.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as "COVID toes," remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as "COVID toes", remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients. Summary: NET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, Setting, and Participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main Outcomes and Measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and Relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.

Non-invasive tools for detection of liver disease in children and adolescents with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multi-organ genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes the CFTR protein. CF-associated liver disease (CFLD) is a common complication; diagnosis is based on clinical, laboratory findings and abdominal imaging. However, non-invasive diagnostic approaches are needed to early detect CFLD, its progression and severity. Recent studies demonstrate a possible role of point shear wave elastography (p-SWE) with liver stiffness measurement (LSM) as a tool for CFLD diagnosis also in children. This non-invasive technique measures liver stiffness to assess liver fibrosis and is suggested to be less operator-dependent compared to ultrasonography. Aim of our prospective observational study is to investigate the role of p-SWE with LSM for CFLD diagnosis in children and adolescents with CF and to compare this finding with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on four factors (FIB-4) and gamma-glutamyl-transpeptidase to platelet ratio (GPR) indices. METHODS: Fifty-nine children with CF, who had routinely undergone abdominal imaging, were consecutively enrolled. Laboratory findings and clinical data were recorded, as abdominal ultrasound and shear wave elastography at baseline. The cases were divided into two groups based on collected data and classified as CFLD and CFnoLD (without liver disease) according to Debray criteria. APRI, FIB-4 and GPR fibrosis indices were also evaluated. RESULTS: Twenty-four/59 (40.7%) were defined as CFLD. LSM test is superior to the APRI (P<0.001), the FIB-4 test (P=0.001) and the GPR test for early detection of liver fibrosis. LSM had an area under receiver operating characteristic (ROC) curve =0.818 (95% CI: 0.702-0.934) compared with APRI (0.571, 95% CI: 0.421-0.722), FIB-4 (0.656, 95% CI: 0.511-0.801) and GPR (0.632, 95% CI: 0.485-0.779). At a cut-off of ≥6.2 LSM show a sensitivity of 75.0% and a specificity of 88.6%. CONCLUSIONS: LSM by transient p-SWE is a non-invasive, highly accessible, reliable, and reproducible test that can be used to assess early detection of liver fibrosis and its severity in children and adolescents with CF, limiting the use of liver biopsy. These preliminary observations point to the need of larger study population to confirm our data.

Health-care organization for the management and surveillance of SARS-CoV-2 infection in children during pandemic in Campania region, Italy.

BACKGROUND: In comparison with adults, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in children has a milder course. The management of children with suspected or confirmed coronavirus disease (COVID-19) needs to be appropriately targeted. METHODS: We designed a hub-and-spoke system to provide healthcare indications based on the use of telemedicine and stringent admission criteria, coordinate local stakeholders and disseminate information. RESULT: Between March 24th and September 24th 2020, the Hub Centre managed a total of 208 children (52% males, median age, 5.2, IQR 2-9.6 years) with suspected or confirmed COVID-19. Among them, 174 were managed in cooperation with family pediatricians and 34 with hospital-based physicians. One hundred-four (50%) received a final diagnosis of SARS-CoV-2 infection. Application of stringent criteria for hospital admission based on clinical conditions, risk factors and respect of biocontainment measures, allowed to manage the majority of cases (74, 71.1%) through telemedicine. Thirty children (28%) were hospitalized (median length 10 days, IQR 5-19 days), mainly due to the presence of persistent fever, mild respiratory distress or co-infection occurring in infant or children with underlying conditions. However, the reasons for admission slightly changed over time. CONCLUSION: An hub-and-spoke system is effective in coordinate territorial health-care structures involved in management paediatric COVID-19 cases through telemedicine and the definition of stringent hospital admission criteria. The management of children with COVID-19 should be based on clinical conditions, assessed on a case-by-case critical evaluation, as well as on isolation measures, but may vary according to local epidemiological changes.

Dieulafoy lesion: two pediatric case reports.

BACKGROUND: Massive gastrointestinal bleeding in children is uncommon. Dieulafoy lesion is an uncommon disease which may lead to massive and repeated upper gastrointestinal hemorrhage. We report two cases of gastric Dieulafoy lesion successfully treated with either band ligation or endoscopic hemoclipping. CASE PRESENTATION: First case report: A previously healthy 18-month-old female infant with E. coli sepsis, pneumonia and respiratory failure with bilateral pneumothorax requiring chest drainage. Over a few days, the patient presented hematemesis and melena with progressively worsening anemia. The esophagogastroduodenoscopy revealed an arterial vessel with eroded apex located between the body and the fundus of the stomach. Two elastic bands were applied which resulted in resolution of hematemesis and melena and improvement of the anemia. Second case report: A 8-year-old male was admitted to our department with sudden massive hematemesis and melena. Clinical examination revealed anemia (hemoglobin, 6.8 g/dl). Esophagogastroduodenoscopy revealed a mucosal erosion with visible vessel located along the small curvature, close to the antrum. Three hemostatic clips were placed on the Dieulafoy lesion and hemostasis was obtained. CONCLUSIONS: we showed that, similar to gastric DL in adult patients,, gastric DL in pediatric patients can be successfully treated with endoscopic therapy, and both hemoclipping and band ligation are suitable techniques.

Management options for cholestatic liver disease in children.

INTRODUCTION: Due to a peculiar age-dependent increased susceptibility, neonatal cholestasis affects the liver of approximately 1 in every 2500 term infants. A high index of suspicion is the key to an early diagnosis, and to implement timely, often life-saving treatments. Even when specific treatment is not available or curative, prompt medical management and optimization of nutrition are of paramount importance to survival and avoidance of complications. Areas covered: The present article will prominently focus on a series of newer diagnostic and therapeutic options of cholestasis in neonates and infants blended with consolidated established paradigms. The overview of strategies for the management reported here is based on a systematic literature search published in English using accessible databases (PubMed, MEDLINE) with the keywords biliary atresia, choleretics and neonatal cholestasis. References lists from retrieved articles were also reviewed. Expert commentary: A large number of uncommon and rare hepatobiliary disorders may present with cholestasis during the neonatal and infantile period. Potentially life-saving disease-specific pharmacological and surgical therapeutic approaches are currently available. Advances in hepatobiliary transport mechanisms have started clarifying fundamental aspects of inherited and acquired cholestasis, laying the foundation for the development of possibly more effective specific therapies.