An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases.Conclusion: PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial. What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases.

/pdf/multisystem-inflammatory-syndrome-in-children-related-to-3a23y2pu07.pdf

Multisystem inflammatory syndrome in children related to COVID-19: a systematic review.

Importance. In April 2020, multiple reports of an association between a hyperinflammatory, Kawasaki-like condition and SARS-CoV-2 were published and termed as pediatric inflammatory multisystem syndrome (PIMS) or multisystem inflammatory syndrome (MIS). A thorough characterization of this syndrome (demographics, presentation, diagnosis, and outcome) is currently lacking. 
Objective. We aimed to perform a systematic review of published cases of this novel multisystem inflammatory syndrome in children associated with COVID-19.
Evidence review. A literature search of Pubmed, Embase, BioRxiv, MedRxiv and COVID-19 specific research repositories (Cochrane COVID‐19 Study Register and the World Health Organization (WHO) COVID‐19 Global Research Database) was conducted from December 30th, 2019 to June 30th, 2020. Publications describing inflammatory syndromes associated with COVID-19 were included. Of 333 unique publications, 229 records were excluded based on title and abstract. After screening the full text, 40 observational studies and case reports were included, comprising 687 cases (published between May 9th, 2020 and June 30th, 2020).
Findings. In contrast to classic Kawasaki disease, epidemiological enrichment for adolescents (median age 9 [6.0-12.3]) and ethnic minorities (35.8% black and 24.5% Hispanic/Latino) was observed. There was a male predominance (59.1%). Apart from obesity (24.4%), pre-existing conditions were infrequent. The majority suffered from gastrointestinal (87.2%) and cardiocirculatory (79.2%) manifestations. Respiratory symptoms (51.2%) were less frequent. Over half of patients (56.3%) presented with hemodynamic shock, and critical care interventions were often necessary (inotropics (56.5%), mechanical ventilation (22.9%), non-invasive ventilation (30.6%), extracorporal membrane oxygenation (ECMO;4.5%)). Anti-SARS-CoV-2 IgG and RT-PCR were positive in respectively 69.4% and 36.7%. Eleven deaths were reported (1.6%). The RCPCH case definition proved to be most comprehensive comprising all single cases. In contrast, WHO and CDC MIS definitions are more stringent, with the CDC case definition often missing severe cases requiring intensive care (n = 33 out of 95 cases).
Conclusions and Relevance. This novel pediatric multisystem hyperinflammatory condition, associated with COVID-19, is characterized by a severe and heterogeneous disease spectrum. Despite frequent intensive care interventions, mortality rate was low and short-term outcome favorable. Long-term follow-up of possible chronic complications and additional clinical research, to elucidate the underlying immunological pathogenesis and possible genetic predisposition is crucial.

/pdf/multisystem-inflammatory-syndrome-in-children-related-to-esdx6ejoxk.pdf

Multisystem inflammatory syndrome in children related to COVID-19: A systematic review

The clinical cases of patients with multisystem inflammatory syndrome (MIS-C) were analyzed via a systematic review and meta-analysis of the clinical findings, treatments, and possible outcomes of articles retrieved via database searches.The authors searched the PubMed, Scielo, Web of Science, Science Direct, EMBASA, EBSCO, and Scopus databases for articles containing the keywords "multisystem inflammatory syndrome in children" or "MIS-C" or "PIMS-TS" or "SIMP" and "COVID-19" or "SARS-CoV-2" published between December 1st, 2019 and July 10th, 2021. Patient characteristics, tissue and organ comorbidities, the incidence of symptoms after COVID-19 infection, treatment, and patient evolution in the articles found were evaluated. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Newcastle-Ottawa Scale (NOS).In total, 98 articles (2275 patients) were selected for demographics, clinical treatment, and outcomes of patients diagnosed with MIS-C. The average age of children with MIS-C, 56.8% of whom were male, was of nine years. Fever (100%), gastrointestinal (GI) (82%), and abdominal pain (68%) were the decisive symptoms for the diagnosis of MIS-C. Shock and/or hypotension were common in patients with MIS-C. Cardiac symptoms (66%) predominated over respiratory (39%) and neurological (28%) symptoms. MIS-C treatment followed the common guidelines for treating children with septic shock and Kawasaki disease (KD) and proved to be effective.This meta-analysis highlights the main clinical symptoms used for the diagnosis of MIS-C, the differences between MIS-C and KD, and the severity of the inflammatory process and urgency for hospital care. 

Multisystem inflammatory syndrome (MIS-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes

Objective This study was conducted to evaluate the persisting Covid-19-related symptoms of the cases included in our study and to assess their cardiac findings to determine the impact of Covid-19 on children's cardiovascular health. Methods In this study, 121 children between the ages of 0- and 18 with Covid-19 were evaluated based on their history, blood pressure values, and electrocardiography and echocardiography results. These findings were compared with the findings of the control group which consisted of 95 healthy cases who were in the same age range as the study group and did not have Covid-19. The results were evaluated using the statistics program, SPSS 21. Results There was no significant difference between the study group and the control group in terms of age, weight, and body mass index. The clinical symptoms (chest and back pain, dizziness, headache, palpitation, fatigue, shortness of breath, loss of balance, coughing) of 37.2% of the cases persisted for at least 1 month after Covid-19 recovery. Statistically significant differences were found in systolic blood pressure, left ventricular ejection fraction, relative wall thickness, and tricuspid annular plane systolic excursion. Conclusion The continuation of some cases' clinical symptoms post-recovery indicates that long Covid infection can be observed in children. The fact that statistically significant differences were observed between the echocardiographic parameters of the study and control groups suggests that Covid-19 may have effects on the cardiovascular system. To shed light on the long Covid cases among children and the infection's cardiac impacts, it would be beneficial to conduct more comprehensive studies on this matter.

Intriguing new faces of Covid-19: persisting clinical symptoms and cardiac effects in children.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 virus. As of the 30th of September 2020, around 34,000,000 cases have been reported globally. Pediatrics with underlying congenital heart disease represent a small yet a critical proportion of these patients. In general, the majority of infected children experience mild to moderate disease with significant interindividual variability in laboratory and radiographic findings. Nevertheless, in healthy children with COVID-19, cardiac involvement has been documented and is attributed to various causes. Myocarditis, arrhythmias, cardiogenic shock, and serious multisystem inflammatory syndrome in children are all encountered. Since COVID-19 is a recent novel disease and based on previous experience with respiratory infections, children with underlying congenital heart disease should be given special attention. To date, little data is available about COVID-19 presentation, complications, and appropriate treatment in this population. However, variable and inconsistent disease presentation and severity have been observed. This paper discusses COVID-19 course of illness in pediatric population with a special emphasis on the cardiac manifestations of the disease in healthy population and also on the disease course in congenital heart disease patients in particular.

/pdf/covid-19-in-pediatric-patients-a-focus-on-chd-patients-4iztv12epq.pdf

COVID-19 in Pediatric Patients: A Focus on CHD Patients

Coronavirus disease-2019 (COVID-19) has been reported to cause significant morbidity in adults, with reportedly a lesser impact on children Cardiac dysfunction has only been described in adults thus far We describe 3 cases of previously healthy children presenting with shock and COVID-19–related cardiac inflammation (Level of Difficulty: Intermediate)

Cardiac Dysfunction and Shock in Pediatric Patients With COVID-19

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Cardiac Dysfunction and Shock in Pediatric Patients With COVID-19