Thrombotic Events in MIS-C Patients: A Single Case Report and Literature Review.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic hyperinflammatory disorder that is associated with a hypercoagulable state and a higher risk of thrombotic events (TEs). We report the case of a 9-year-old MIS-C patient with a severe course who developed a massive pulmonary embolism that was successfully treated with heparin. A literature review of previous TEs in MIS-C patients was conducted (60 MIS-C cases from 37 studies). At least one risk factor for thrombosis was observed in 91.7% of patients. The most frequently observed risk factors were pediatric intensive care unit hospitalization (61.7%), central venous catheter (36.7%), age >12 years (36.7%), left ventricular ejection fraction <35% (28.3%), D-dimer >5 times the upper limit of normal values (71.9%), mechanical ventilation (23.3%), obesity (23.3%), and extracorporeal membrane oxygenation (15%). TEs may concurrently affect multiple vessels, including both arterial and venous. Arterial thrombosis was more frequent, mainly affecting the cerebral and pulmonary vascular systems. Despite antithrombotic prophylaxis, 40% of MIS-C patients developed TEs. Over one-third of patients presented persistent focal neurological signs, and ten patients died, half of whom died because of TEs. TEs are severe and life-threatening complications of MIS-C. In case with thrombosis risk factors, appropriate thromboprophylaxis should be promptly administered. Despite proper prophylactic therapy, TEs may occur, leading in some cases to permanent disability or death.

Gastrointestinal, hepatic and pancreatic manifestations of COVID-19 in children.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a well-established respiratory tract pathogen. Recent studies in adults and children have shown an increasing number of patients reporting gastrointestinal manifestations of SARS-CoV-2 infection such as diarrhoea, nausea, vomiting and abdominal pain. SARS-CoV-2 RNA can be detected in faeces for an extended period, even after respiratory samples have tested negative and patients are asymptomatic. However, faecal-oral transmission has not yet been proven. In this article, the latest evidence on gastrointestinal, hepato-biliary, and pancreatic manifestations in children with coronavirus disease-19 and multisystem inflammatory syndrome will be analysed.

Anticoagulation and Thrombotic Events in the Multisystem Inflammatory Syndrome in Children: Experience of a Single-center Cohort and Review of the Literature.

The multisystem inflammatory syndrome in children (MIS-C) is a severe clinical entity affecting the coagulative system; although thromboembolic events (TEs) are not common, most patients receive anticoagulation. We retrospectively assessed patients below 18 years admitted with MIS-C at Meyer Children's Hospital (Florence, Italy). Data on baseline clinical and laboratory presentation, treatment, and outcome, including differences between patients with and without thrombotic prophylaxis, were analyzed. Thirty-two children 1 to 15 years were included. Seventeen patients (53.1%) required intensive care admission, 2 (8.7%) had obesity, 7 (30.4%) a central venous catheter, and 14 (43.8%) an impaired cardiac function. Twelve patients (37.5%) received prophylactic anticoagulation: they had more frequent cardiac involvement (91.7 vs. 50%, P =0.02) and higher ferritin levels (median 1240 vs. 501.5 ng/mL, P <0.001). No differences were found in median d -dimers between the 2 groups. Twenty-one patients (65.6%) had d -dimers >5×upper limit of normal but the indication for anticoagulation was not driven by d -dimers. No patient had hemorrhagic events and only 1 patient (3.1%) had a superficial thrombotic event (under thromboprophylaxis). Our series and the available literature data on MIS-C and thromboembolic events suggest that TEs are a rare complication of MIS-C that is frequently associated with high d -dimer values. However, also in MIS-C, the well-established risk factors of pediatric TEs (ie, older age, central venous catheter, obesity, and cancer) should guide thromboembolic risk assessment.

Sensitivity of three commercial tests for SARS-CoV-2 serology in children: an Italian multicentre prospective study.

BACKGROUND: US Food and Drug Administration has issued Emergency Use Authorizations for hundreds of serological assays to support Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) diagnosis. The aim of this study is to evaluate, for the first time in children, the performance of three widely utilized SARS-CoV-2 serology commercial assays, Diesse Diagnostics (IgG, IgA, IgM) and Roche Diagnostics, both Roche Nucleocapsid (N) IgG and Roche Spike (S) IgG assays. METHODS: Sensitivity and 95% confidence intervals (CIs) were estimated for each of the three different serological tests and mixed and direct comparison were performed. Univariate and multivariate Poisson regression models were fitted to calculate incidence rate ratios and 95% CIs as estimate of the effects of age, gender, time on the serology title. A p-value < 0.05 indicated statistical significance. RESULTS: Overall, 149 children were enrolled in the study. A low sensitivity was found for Diesse IgA, IgM and IgG. Compare to Diesse, Roche S had a higher sensitivity at 15-28 days from infection (0.94, 95%CI: 0.73-1.0) and Roche N at 28-84 days (0.78, 95%CI: 0.58-0.91). When a direct comparison of IgG tests sensitivity was feasible for patients with pairwise information, Roche S and Roche N showed a statistically significant higher sensitivity compared to Diesse in all the study periods, whereas there was no difference between the two Roche tests. CONCLUSION: Roche S and Roche N serology tests seem to better perform in children. Large prospective studies are needed to better define the characteristics of those tests.

Neurological Involvement in Children with COVID-19 and MIS-C: A Retrospective Study Conducted for More than Two Years in a Pediatric Hospital.

This study aimed to evaluate the type and severity of neurological involvement in children with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) and compare these findings between the two groups. Children hospitalized with the diagnosis of COVID-19 or MIS-C at Meyer Children's Hospital between February 2020 and June 2022 were retrospectively studied. One hundred twenty-two patients were enrolled, 95 in the COVID-19 group and 27 in the MIS-C group. In the COVID-19 group, impairment of consciousness was found in 67.4% of patients, headache in 18.9% and about 16.8% of patients experienced seizures. In this group, three patients were diagnosed with arterial ischemic stroke and one patient was diagnosed with Guillain-Barré syndrome (GBS). In the MIS-C group, about 70% of patients experienced consciousness impairment, about 20% behavioral changes, and another 20% mood deflection. Neurological symptoms and signs were highly heterogeneous and could be differentiated in COVID-19 and MIS-C. Consciousness impairment remained the most frequent manifestation in both groups, potentially underlying an encephalopathy. We also highlight the importance of considering psychiatric symptoms in children with COVID-19 and/or MIS-C. Most neurological manifestations were mild in our series; however, severe complications such as ischemic stroke and GBS are worthy of note.

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature. METHODS: Subjects under 90 days of age admitted to 35 Italian institutions for COVID-19 were included. The severity of COVID-19 was scored as mild/moderate or severe/critical following the classification reported in the literature by Venturini, Dong, Kanburoglu, and Gale. To assess the diagnostic accuracy of each classification system, we stratified all enrolled patients developing a posteriori severity score based on clinical presentation and outcomes and then compared all different scores analyzed. RESULTS: We included 216 infants below 90 days of age. The most common symptom was fever, followed by coryza, poor feeding, cough, and gastrointestinal manifestations. According to Venturini, Dong, Kanburoglu, and Gale's severity scores, 18%, 6%, 4.2%, and 29.6% of infants presented with severe/critical disease, respectively. A correlation analysis between these four scores and the a posteriori severity score assigned to all enrolled subjects was performed, and a crescent strength of correlation from Gale (R = 0.355, p < 0.001) to Venturini (R = 0.425, p < 0.001), Dong (R = 0.734, p < 0.001), and Kanburoglu (R = 0.859, p < 0.001) was observed. CONCLUSIONS: The percentage of infants with severe COVID-19 varies widely according to the score systems. A unique clinical score should be designed for neonates and infants with COVID-19.

Thromboembolic complications in children with COVID-19 and MIS-C: A narrative review.

COVID-19 and multisystem inflammatory syndrome in children (MIS-C) have been associated with a higher incidence of hypercoagulability and thromboembolic events (TEs), even in children, leading to relevant morbidity, and mortality. However, our understanding of such complications in childhood is limited. To better understand the incidence, clinical manifestations, risk factors, and management of COVID-19 and MIS-C-related TEs in children, a review of the current literature and a brief update on pathophysiology are given. Sixty-two studies, describing 138 patients with TEs associated with COVID-19 or MIS-C, were included. The overall number of TEs was 157, as 16 patients developed multiple TEs: venous TEs represented the majority (54%), followed by arterial thrombosis (38%, mainly represented by arterial ischemic stroke-AIS), and intracardiac thrombosis (ICT) (8%). Within the venous TEs group, pulmonary embolism (PE) was the most frequent, followed by deep venous thrombosis, central venous sinus thrombosis, and splanchnic venous thrombosis. Notably, 10 patients had multiple types of venous TEs, and four had both venous and arterial thrombosis including a newborn. Most of them (79 cases,57%) had at least one predisposing condition, being obesity the most frequent (21%), especially in patients with PE, followed by malignancy (9%). In 35% of cases, no data about the outcome were available About one-third of cases recovered, 12% improved at discharge or follow-up, and 6% had persistent neurological sequelae. The mortality rate was 12%, with death due to comorbidities in most cases. Most fatalities occurred in patients with arterial thrombosis. Pediatricians should be aware of this life-threatening possibility facing children with SARS-CoV-2 infection or its multisystemic inflammatory complication, who abruptly develop neurological or respiratory impairment. A prompt intensive care is essential to avoid severe sequelae or even exitus.

Erythema Nodosum in Children: A Narrative Review and a Practical Approach.

Erythema nodosum (EN) is the most frequent form of panniculitis in children. We performed a literature review analyzing studies on pediatric EN published from 1990 to February 2022. EN is rare in pediatric age. It can be primary/idiopathic in 23-55% cases, or secondary in 47-77% cases. Secondary EN is related to a wide variety of conditions including infectious diseases, autoimmune disorders, malignancy, drugs, vaccinations, and pregnancy. The diagnosis of EN is clinical, based on the acute appearance of painful and red nodules localized to lower limbs, bilaterally distributed. If EN is diagnosed, basic work-up should include inflammatory markers, serum aminotransferases, lactate dehydrogenase, creatinine, protein electrophoresis, immunoglobulins, testing for streptococcal infection, and a tuberculin skin test. Based on the medical history and associated manifestations, further laboratory and radiological exams should be performed. The prognosis of EN is excellent, with spontaneous resolution in most patients within 2-6 weeks. Treatment, if needed, is addressed to the underlying condition. Despite being a rare manifestation in children, EN can be isolated or the first manifestation of a systemic or infectious condition. EN diagnosis is clinical, and a high index of suspicion is needed to perform investigations for the underlying disorders.

Parent-Collected Nasal Swab for Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Children.

This cross-sectional study, including children hospitalized for severe acute respiratory syndrome coronavirus 2 infection, demonstrates for the first time that nonhealthcare worker parents perform similarly to healthcare workers in the administration to their children of an unsupervised nasal swab for severe acute respiratory syndrome coronavirus 2 detection by following written instructions and video tutorials.

Impact of SARS-CoV-2 Pandemic and Strategies for Resumption of Activities During the Second Wave of the Pandemic: A Report From Eight Paediatric Hospitals From the ECHO Network.

The Severe Acute Respiratory Syndrome CoronaVirus type 2 (SARS-CoV-2) pandemic impacted the organization of paediatric hospitals. This study aimed to evaluate the preparedness for the pandemic among a European network of children's hospitals and to explore the strategies to restart health care services. A cross-sectional, web-based survey was distributed in May 2020 to the 13 children's tertiary care hospitals belonging to the European Children's Hospitals Organisation. Responses were obtained from eight hospitals (62%). Significant reductions were observed in accesses to the emergency departments (41.7%), outpatient visits (35.7%), intensive and non-intensive care unit inpatient admissions (16.4 and 13%, respectively) between February 1 and April 30, 2020 as compared with the same period of 2019. Overall, 93 children with SARS CoV-2 infection were admitted to inpatient wards. All the hospitals created SARS-CoV-2 preparedness plans for the diagnosis and management of infected patients. Routine activities were re-scheduled. Four hospitals shared their own staff with adult units, two designated bed spaces for adults and only one admitted adults to inpatient wards. The three main components for the resumption of clinical activities were testing, source control, and reorganization of spaces and flows. Telemedicine and telehealth services were used before the SARS-CoV-2 pandemic by three hospitals and by all the hospitals during it. Conclusion: The present study provides a perspective on preparedness to SARS-CoV-2 pandemic among eight large European children's hospitals, on the impact of the pandemic on the hospital activities and on the strategies adopted to restart clinical activities.

Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

Nasal Swab as Preferred Clinical Specimen for COVID-19 Testing in Children.

The first pediatric study demonstrating significantly higher positivity rate of nasal (mid-turbinate) swab testing over oropharyngeal swab testing in detecting SARS-CoV-2 (Fisher exact test 0.046, Cohen K 0.43, confidence interval 95%, 0.014-0.855). Benefits might include lower collection-related hazard for healthcare workers. We recommend it as preferred choice for swab-based SARS-CoV-2 testing in children.