Risk Factors Associated with Intensive Care Admission in Children with Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome (MIS-C) in Latin America: A Multicenter Observational Study of the REKAMLATINA Network.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 varies widely in its presentation and severity, with low mortality in high-income countries. In this study in 16 Latin American countries, we sought to characterize patients with MIS-C in the pediatric intensive care unit (PICU) compared with those hospitalized on the general wards and analyze the factors associated with severity, outcomes, and treatment received. Study Design: An observational ambispective cohort study was conducted including children 1 month to 18 years old in 84 hospitals from the REKAMLATINA network from January 2020 to June 2022. Results: A total of 1239 children with MIS-C were included. The median age was 6.5 years (IQR 2.5-10.1). Eighty-four percent (1043/1239) were previously healthy. Forty-eight percent (590/1239) were admitted to the PICU. These patients had more myocardial dysfunction (20% vs 4%; P < 0.01) with no difference in the frequency of coronary abnormalities (P = 0.77) when compared to general ward subjects. Of the children in the PICU, 83.4% (494/589) required vasoactive drugs, and 43.4% (256/589) invasive mechanical ventilation, due to respiratory failure and pneumonia (57% vs 32%; P = 0.01). On multivariate analysis, the factors associated with the need for PICU transfer were age over 6 years (aOR 1.76 95% CI 1.25-2.49), shock (aOR 7.06 95% CI 5.14-9.80), seizures (aOR 2.44 95% CI 1.14-5.36), thrombocytopenia (aOR 2.43 95% CI 1.77-3.34), elevated C-reactive protein (aOR 1.89 95% CI 1.29-2.79), and chest x-ray abnormalities (aOR 2.29 95% CI 1.67-3.13). The overall mortality was 4.8%. Conclusions: Children with MIS-C who have the highest risk of being admitted to a PICU in Latin American countries are those over age six, with shock, seizures, a more robust inflammatory response, and chest x-ray abnormalities. The mortality rate is five times greater when compared with high-income countries, despite a high proportion of patients receiving adequate treatment.

Three-Dimensional Echocardiography and Global Longitudinal Strain in Follow-Up After Multisystem Inflammatory Syndrome in Children: Six-Month, Single-Center, Prospective Study.

OBJECTIVE: To assess the potential long-term cardiac effects after multisystem inflammatory syndrome in children (MIS-C) with cardiovascular involvement in the acute phase. STUDY DESIGN: Our prospective study involved children consecutively diagnosed with MIS-C between October 2020 and February 2022 and followed 6 weeks and 6 months after the disease. In patients with severe cardiac involvement during the acute phase, an additional check-up after 3 months was scheduled. In all patients at all check-ups, 3-dimensional echocardiography and global longitudinal strain (GLS) were used to assess ventricular function. RESULTS: The study enrolled 172 children aged 1-17 years (median, 8 years). The means of ejection fraction (EF) and GLS for both ventricles were within normal limits after 6 weeks with no relationship with initial severity: left ventricular EF (LVEF) 60% (59%-63%), LV GLS -21.08% (-18.63% to -23.2%), right ventricular (RV) EF 64% (62%-67%), and RV GLS -22.8% (-20.5% to -24.5%). Further, statistically significant improvement of LV function was observed after 6 months-LVEF 63% (62%-65%) and LV GLS -22.55% (-21.05% to -24.25%; P < .05); however, RV function remained unchanged. The group with severe cardiac involvement showed LV function recovery pattern with no significant improvement between 6 weeks and 3 months after MIS-C, while still improving between 3 and 6 months after discharge. CONCLUSIONS: LV and RV function is within normal limits 6 weeks after MIS-C regardless of severity of cardiovascular involvement; LV function improves further between 6 weeks and 6 months after the disease. The long-term prognosis is optimistic with full recovery of cardiac function.

Characteristics and clinical outcomes of COVID-19 in children: a hospital-based surveillance study in Latin America's hardest-hit city.

Background: In 2020, Brazil became the epicentre of the coronavirus disease (COVID-19) pandemic in Latin America, resulting in an unparalleled health catastrophe. Nevertheless, comprehensive clinical reports in Brazilian children are not available. Methods: This retrospective, hospital-based, active surveillance study was performed to identify paediatric patients with COVID-19 who presented at a private academic medical centre in a large urban area between March 2020 and March 2021. Clinical and demographic information was analysed for those requiring hospitalization, those with severe illness and those with clinical syndromes. Results: In total, 964 symptomatic cases were evaluated; of these, 17.7% required hospitalization, and 27.5% of hospitalized cases were classified as severe/critical. Acute bronchiolitis and pneumonia were the most common causes of hospitalization among the severe cases. Twenty-seven hospitalized children fulfilled the diagnostic criteria for multi-system inflammatory syndrome (median age 29 months; 85.2% cases were non-severe). A significant co-existing condition was present in 29% of hospitalized children. The risk of hospitalization was higher in children with at least one comorbidity, children aged <2 years and obese children. Increased risk of severe disease was described among those with leukopenia, leukocytosis or any significant comorbidity. No deaths occurred among the study population. Conclusion: Although most children with COVID-19 experienced mild disease, and no deaths occurred among the study population, a significant proportion of cases required hospitalization and developed severe illness. Obesity, young age, underlying comorbidity, leukopenia and leukocytosis were risk factors for hospitalization or severe disease.

Enfermedad tipo Kawasaki relacionado a COVID-19. Manejo perioperatorio de un caso pediátrico / Kawasaki-like disease related to COVID-19. Perioperative management of a pediatric case

The recently identified COVID-19-related Kawasaki-like disease has been considerad one of the phenotypes of the cardiovascular manifesta- tions of the Pediatric Multisystem Inflammatory Syndrome associated with SARS-CoV-2 (PIMS-TS), which stands out for few respiratory symptoms and múltiple manifestations cardiovascular, the most important being dilation and eventual coronary aneurysms associated or not with cardio- genic shock. The literature is scarce, so perioperative management is challenging for the anesthesiology team. We present the case of an infant with severe cardiovascular manifestations as a result of this disease that required anesthetic interventions to perform a plethysmography and amputation of his lower extremity. The article describes the most relevant considerations in the perioperative management of patients with this pathology.

La enfermedad tipo Kawasaki relacionada a COVID-19 recientemente identificada ha sido considerada como uno de los fenotipos de las manifestaciones cardiovasculares del Síndrome Inflamatorio Multisistémico Pediátrico asociado a SARS-CoV-2 (PIMS-TS), que destaca por escasos síntomas respiratorios y múltiples manifestaciones cardiovasculares, siendo la más importante, la dilatación y eventuales aneurismas coronarios asociados o no a shock cardiogénico. La bibliografía es escasa, por lo que, el manejo perioperatorio es desafiante para el equipo anestesiológico. Presentamos el caso de un lactante con manifestaciones cardiovasculares severas producto de esta enfermedad que requirió intervenciones anestésicas para la realización de una pletismografía y la amputación de su extremidad inferior. El artículo describe las consideraciones más relevantes en el manejo perioperatorio de los pacientes con esta patología.

Multisystem inflammatory syndrome in children related to COVID-19: Data from a Mexican national referral children's hospital.

Objectives: To describe characteristics of patients with the pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS)/multisystem inflammatory syndrome in children (MIS-C) and to identify factors associated with admission to the pediatric intensive care unit (PICU) in the Mexican children without coronavirus disease 2019 (COVID-19) vaccination. Methods: This was a cross-sectional study performed at Hospital Infantil de Mexico Federico Gomez, a referral children's hospital in Mexico. The study included all cases that met the criteria for PIMS-TS/MIS-C, unvaccinated, between March 2020 and January 2022. The primary outcome was the admission to PICU. Associations of PICU admission with demographic and clinical variables were estimated using logistic regression analyses. Results: We identified a total of 90 cases, with a median age of 7.5 years old, 47 (52.2%) girls. A previously healthy status was recorded in 76 (85%) children. All patients had positive PCR, serology test, or COVID-19 exposure. PICU admission was reported in 41 (45.6%) children. No deaths were reported. Patients received as treatment only corticosteroids in 53.3% of the cases. In univariable analyses, baseline factors associated with PICU admission were older age, hypotension or shock, positive PCR test, hypoalbuminemia, elevated procalcitonin, ferritin, and lymphopenia. Age, shock at admission, and hypoalbuminemia remained independently associated in the multivariable analysis adjusted by gender and previously healthy status. Conclusion: We found a high proportion of previously healthy children in patients with PIMS-TS/MIS-C in our center. Critical care attention was received by nearly half of the children. The main treatment used was steroids. Age, shock at admission, and hypoalbuminemia were factors associated with PICU admission.

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

Abstract Objective: 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. Sources: 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). Findings: 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. Conclusions: 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: 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. SOURCES: 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). FINDINGS: 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. CONCLUSIONS: 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.

Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with covid-19 in critically ill patients: an observational multicenter study (MISCO study).

BACKGROUND: The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is widespread and presents a very low mortality rate in high-income countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries and the factors associated with the rate of mortality and patients with critical outcomes. METHODS: An observational cohort study was conducted in 14 pediatric intensive care units (PICUs) in Colombia between April 01, 2020, and January 31, 2021. Patient age ranged between one month and 18 years, and each patient met the requirements set forth by the World Health Organization (WHO) for MIS-C. RESULTS: There were seventy-eight children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old, and 56 % were male. 35 % of patients (29/78) were obese or overweight. The PICU stay per individual was six days (IQR 4-7), and 100 % had a fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87 % (68/78) had shock or systolic myocardial dysfunction (78 %). Coronary aneurysms were found in 35 % (27/78) of cases, and pericardial effusion was found in 36 %. When compared to existing data in high-income countries, there was a higher mortality rate observed (9 % vs. 1.8 %; p=0.001). When assessing the group of patients that did not survive, a higher frequency of ferritin levels was found, above 500 ngr/mL (100 % vs. 45 %; p=0.012), as well as more cardiovascular complications (100 % vs. 54 %; p = 0.019) when compared to the group that survived. The main treatments received were immunoglobulin (91 %), vasoactive support (76 %), steroids (70.5 %) and antiplatelets (44 %). CONCLUSIONS: Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. The observed inflammatory response and cardiovascular involvement were conditions that, added to the later presentation, may explain the higher mortality seen in these children.

Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C).

Endothelial insult and damage is one of the reported consequences of SARS-CoV-2 infection. It has been associated with severe inflammation, thrombotic phenomena and profound hypoxemia in critically ill patients. Endothelial activation leads to a loss of the endothelium's antithrombotic properties which, under normal conditions, are maintained by the endothelial glycocalyx, a carbohydrate-rich layer that covers the luminal surface of endothelial cells. In children, one of the serious forms of SARS-CoV-2 virus disease (COVID-19) is multisystem inflammatory syndrome (MIS-C). This new disease is characterized by a large inflammatory response and frequent cardiovascular, cutaneous and gastrointestinal disorders. We describe the first two cases of critically ill children with MIS-C who evidenced a large inflammatory response associated with elevated plasma and imaging biomarkers of endothelial activation and endothelial glycocalyx degradation. This microcirculation involvement in MIS-C could, at least partially, explain some of the clinical manifestations and laboratory and imaging alterations found in these patients. These findings contribute to a better understanding of this disease and suggest that medications to modulate the inflammatory response and protect or restore the endothelial glycocalyx should be considered in future studies.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 Treated with Tocilizumab.

We describe a case of Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in an 8-year-old child. The patient developed multiorgan dysfunction, including mixed shock, cardiac dysfunction with myocarditis, pneumonia, acute kidney failure, and gastrointestinal involvement characterized by inflammation of the wall of the bowel and pancreatitis. After treatment with Tocilizumab and corticoid therapy, he presented clinical improvement and normalization of inflammatory markers. PIMS-TS is a new disease developed in a small percentage of patients, so a high degree of suspicion is necessary to establish the diagnosis. Supportive care is of paramount importance. The use of Tocilizumab to control the inflammatory response is likely to be beneficial, but the best immunotherapeutic agent has not yet been established. Randomized clinical studies should be run to determine the best treatment.