Multisystemic inflammatory syndrome in children after severe acute respiratory syndrome coronavirus 2 infection: a clinical analysis of four cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features and treatment strategies of multisystemic inflammatory syndrome in children (MIS-C) after severe acute respiratory syndrome coronavirus 2 infection.@*METHODS@#A retrospective analysis was performed on the medical data of four children with MIS-C who were admitted to the Department of Cardiology, Xuzhou Children's Hospital, Xuzhou Medical Universityfrom January to February 2023.@*RESULTS@#All four children had multiple organ involvements and elevated inflammatory markers, with a poor response to standard therapy for Kawasaki disease after admission. Two children were treated with intravenous immunoglobulin therapy pulse therapy twice, and all four children were treated with glucocorticoids. The children had a good prognosis after the treatment.@*CONCLUSIONS@#MIS-C often appears within 4-6 weeks or a longer time after severe acute respiratory syndrome coronavirus 2 infection, and anti-inflammatory therapy in addition to the standard treatment regimen for Kawasaki disease can help to achieve a favorable treatment outcome.

Factores de Riesgo de Hospitalización en Camas Básicas y Críticas asociados a Síndrome Inflamatorio Multisistémico Pediátrico (SIM) relacionado a COVID-19 de Niños, Niñas y Adolescentes: Revisión Sistemática Exploratoria / Risk Factors of Hospitalization in Basic and Critical Cases associated with Pediatric Multisystemic Inflammatory Syndrome (SIM) related to COVID-19 in Boys, Girls and Adolescents: Exploratory Systematic Review

Introducción. Introducción. La pandemia por SARS-CoV-2 en pediatría ha tenido un bajo impacto en niños y niñas adolescentes (NNA) debido a que un gran porcentaje son asintomáticos o desarrollan síntomas leves. No obstante, se han reportado casos de síndrome inflamatorio multisistémico pediátrico (SIM) por este virus, el cual afecta a múltiples órganos y sus manifestaciones se asemejan a la enfermedad de Kawasaki. La mayoría ha requerido hospitalización en unidades críticas (UCI). A pesar de la vigilancia epidemiológica de esta enfermedad, no se han reportado factores de riesgo (FR) para hospitalización. Objetivo. Explorar en la literatura los FR asociados a hospitalización en camas básicas y críticas de NNA con SIM relacionado a COVID-19. Métodos. Revisión sistemática exploratoria de bases de datos Pubmed, Epistemonikos, Lilacs y Scielo desde el año 2020, con un rango etario de 0 a 19 años, con estrategia de búsqueda sensible para FR de hospitalización en camas básicas y críticas por SIM. Resultados. De 84 artículos se seleccionaron 7. Las manifestaciones clínicas incluyeron fiebre persistente, síntomas gastrointestinales y parámetros inflamatorios severos. También se reporta asociación a comorbilidades y estrato socioeconómico bajo. El ingreso mediano a UCI fue de un 60%, y la mortalidad por SIM fue menor a un 2%, pero de mayor magnitud comparado con los ingresos por COVID-19 en este grupo etario. Los FR de ingreso a UCI fueron asociados a dolor abdominal [OR 1,7 (IC95% 1,2; 2,7)] y a mayor edad, con OR ajustado de 1,9 [IC95%1,4; 6] para edad de 6 a 12 años, OR ajustado de 2,6 [IC95% 1,8; 3,8] para edad de 13 a 20 años. La elevación de proteína C reactiva, troponina, ferritina, dímero D, péptido natriurético cerebral (BNP), BNP N-terminal pro tipo B o interleucina-6, y/o recuentos reducidos de plaquetas, linfocitos o albúmina se asociaron a ingreso a UCI. La etnia afroamericana se asoció a mayor ingreso a UCI con OR de 1,6 [IC95% 1,0; 2,4]. Conclusión. Los FR para hospitalización de NNA con SIM, reportados y seleccionados en la literatura, son edad sobre los 6 años, etnia afroamericana, presencia de comorbilidades y nivel socioeconómico bajo. Para el ingreso a UCI, se suma a esto, compromiso clínico respiratorio y/o gastrointestinal, y presencia de parámetros inflamatorios elevados. La mortalidad fue inferior al 2%, pero significativamente mayor que la mortalidad por infección COVID-19 exclusiva.

Background. SARS-CoV-2 pandemic in pediatrics population (children and adolescents) has low impact in due to large percent of asymptomatic or mild symptoms. However, since March 2020, cases of pediatric multisystemic inflammatory syndrome (PMIS) have been reported, which affects multiple organs and its main manifestations resemble Kawasaki disease. This group frequently required hospitalization in critical care units (ICU), and despite epidemiological surveillance of this disease, no risk factors (RF) for hospitalization of these children has been reported. Objetive. To explore RF in literature associated with pediatric hospitalization in basic and critical care beds from children and adolescents with PMIS related to COVID-19. Methodology. exploratory systematic review of Pubmed, Epistemonikos, Lilacs and Scielo databases, with limits: publication date from 2020 until now, and age range from 0 to 19 years. We made a sensitive search strategy for RF of pediatric hospitalization in basic and critical beds by PMIS. Results. clinical manifestations of hospitalized patients included persistent fever (3 to 5 days), gastrointestinal symptoms (vomiting, nausea, diarrhea and abdominal pain), and inflammatory laboratory parameters in highly ranges. It is also reported an association with presence of comorbidities and low socioeconomic status. The median admission to ICU was 60%, and mortality less than 2%, but greater magnitude compared to COVID-19 mortality. RF for ICU admission were associated with older age, with adjusted OR of 1.9 [CI95% 1.4; 6] for age 6 to 12 years, adjusted OR of 2.6 [CI95% 1.8; 3.8] for age 13 to 20 years, and abdominal pain [OR 1.7 (CI95% 1.2; 2.7)]. Among laboratory tests, elevated C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro-B-type BNP or interleukin-6, and/or reduced platelet, lymphocyte or albumin counts were associated with ICU admission. African-American ethnicity was also associated with higher ICU admission with OR of 1.6 [CI95% 1.0; 2.4]. Conclusion. RFs for hospitalization of children with PMIS reported and selected in the literature were: age over 6 years, Afro-American ethnicity, presence of comorbidities and low socioeconomic level. In addition to this, for ICU admission, it is reported respiratory and/or gastrointestinal clinical involvement, and elevated inflammatory parameters presence. Mortality was less than 2%, but significantly higher than mortality due to exclusive COVID-19 infection.

Enfermedad de Kawasaki, enfermedad similar a Kawasaki y MIS-C asociado a COVID-19 en niños: revisión sistemática / Kawasaki disease, Kawasaki-like disease, and MIS-C associated with COVID-19 in children: systematic review

Resumen Objetivo: Sintetizar las características epidemiológicas y clínicas de los niños de COVID-19 con EK, KLD y MIS-C. Métodos: Se realizó una búsqueda en 4 bases de datos y preprints hasta el 31 de Mayo del 2021. Se incluyeron reportes/series de caso que evaluaron las caracte rísticas clínicas del EK, KLD o MIS-C en pacientes pediátricos con COVID-19. Resultados: Se incluyeron 16 estudios (seis informes de casos y diez series de casos, 367 pacientes en total, 58 pacientes con EK, 87 con KLD y 290 pacientes con MIS-C); con edades entre los 6 meses y los 10 años, y el 62% eran mujeres. Se observó COVID-19 positivo en 75,2%. Respecto a EK, KLD y MIS-C, las características clínicas repor tadas fueron compatibles con los cuadros diagnósticos estandarizados en el contexto de COVID-19. La duración de la hospitalización fue de 5 a 14 días para EK y de 4,3 a 13 para MIS-C. Once pacientes con MIS-C (2,8%) necesitaron ECMO. Seis pacientes con MIS-C fueron reportados muertos. Ocho estudios reportaron pacientes en la UCI. Conclusiones: EK o KLD puede asociarse a COVID-19 en niños, y pueden complicarse con MIS-C. El tiempo de hospitalización es prolongado si se presenta EK o KLD asociado a COVID-19 en niños.

Abstract Objective: To synthesize the epidemiological and clinical characteristics of COVID-19 children with MIS-C, KLD and EK. Methods: Databases and preprints were searched until May 31, 2021. Reports/case series that evaluated the clinical features of EK, KLD, or MIS-C in pediatric patients with COVID-19 were included. Results: Sixteen studies were included (six case reports and ten case series, 367 patients total, 58 patients with EK, 87 with KLD, and 290 patients with MIS-C); with ages ranging from 6 months to 10 years, and 62% were female. Positive COVID-19 was observed in 75.2%. Regarding EK, KLD and MIS-C, the reported clinical characteristics were compatible with the standardized diagnostic pictures in the context of COVID-19. The duration of hospitalization was 5 to 14 days for EK and 4.3 to 13 for MIS-C. Eleven patients with MIS-C (2.8%) needed ECMO. Eleven patients with MIS-C (2.8%) needed ECMO. Six patients with MIS-C were reported dead. Eight studies reported patients in the ICU. Conclusions: Children with COVID-19 develop EK or KLD, and can be complicated by MIS-C. Prevention, diagnosis, and treatment measures are needed.

Síndrome inflamatorio multisistémico en niños asociado a COVID-19

RESUMEN Introducción: La afectación de la COVID-19 en niños es leves o asintomática, en la mayoría de los casos, pero un pequeño porcentaje presenta enfermedades graves que requieren ingreso en la unidad de cuidados intensivos pediátricos, uno de ellos es el síndrome inflamatorio multisistémico en niños asociado a COVID-19, caracterizado por fiebre, reactantes de fase aguda elevado y afectación de varios órganos. Objetivo: Informar dos casos con síndrome inflamatorio multisistémico en niños asociado a COVID-19, en la Ciudad de Huancayo - Perú. Presentación de los casos: Caso 1: paciente varón de 3 años, con un tiempo de enfermedad de 12 días que inicio con síntomas de vías respiratorias superiores y fiebre por tres días y con malestar general y 4 días antes del ingreso presenta fiebre en forma persistente, dolor abdominal tipo cólico asociado a vómitos, también inicia con exantema purpúrica en miembros inferiores. Cuenta como antecedente padre con prueba de PCR - RT para COVID-19 positivo 3 semanas antes del ingreso del menor. Caso 2: paciente varón de 10 años, con antecedente de neumonía por COVID-19, 15 días antes del ingreso, acude con un tiempo de enfermedad de 3 días caracterizado por fiebre, fatiga y palpitaciones que se exacerban con la actividad física. Conclusión: El síndrome inflamatorio multisistémico en niños asociado a COVID-19 es una enfermedad nueva que requiere un manejo multidisciplinario en una unidad de cuidados intensivos pediátricos.

ABSTRACT Introduction: The condition of COVID-19 in children is mild or asymptomatic in most cases, but a small percentage has serious diseases that require admission to the pediatric intensive care unit, one of them is the multisystemic inflammatory syndrome in children associated with COVID-19, characterized by fever, high acute phase reactants and involvement of various organs. Objective: To report two cases with multisystemic inflammatory syndrome in children associated with COVID-19, in Huancayo City - Peru. Case report: Case 1: A 3-year-old male patient had 12-day illness period that began with upper respiratory symptoms, fever for three days, general discomfort and 4 days before admission, he showed with persistent fever, colicky abdominal pain associated with vomiting, also he had a purpuric rash on the lower limbs. As a background, his father tested positive for the PCR-RT test for COVID-19, 3 weeks before the child's admission. Case 2: A 10-year-old male patient, with a history of COVID-19 pneumonia, 15 days before admission, he had a 3-day illness period characterized by fever, fatigue and palpitations that exacerbated by physical activity. Conclusions: The multisystemic inflammatory syndrome in children associated with COVID-19 is a new disease that requires multidisciplinary management in a pediatric intensive care unit.

Síndrome inflamatorio multisistémico pediátrico (SIMS) asociado con el SARS-CoV-2: Un estudio de cohorte retrospectivo / SARS-CoV-2-associated pediatric multisystemic inflammatory syndrome: A retrospective cohort study

Introduccion: El Síndrome inflamatorio multisistémico pediátrico (SIMS) asociado con el SARS-CoV-2 es una enfermedad aguda acompañada de un síndrome hiperinflamatorio, con falla multiorgánica y shock, asociada a la infección por SARS CoV2, que produce alta morbilidad en la población pediátrica, que hasta el momento es la afectada por este síndrome. Objetivo: Evaluar las características diferenciales del síndrome multisistémico inflamatorio asociado al SARS-COV-2 (SIMS) en niños. Métodos: se realizó un estudio de cohorte retrospectivo. La definición de SIMS se basó en los criterios de la OMS. Los pacientes con COVID-19 relacionados temporalmente se incluyeron como controles. Resultados: se incluyeron 25 pacientes con SIMS y 75 controles. El modelo de regresión logística múltiple de las variables que mostraron ser significativas en el análisis univariado reveló que la edad ≥ 2 años (OR 24,7; IC del 95%: 1,03 -592,4; P = 0,048), la linfopenia (OR 9,03; IC del 95%: 2,05-39,7; P = 0,004), y el recuento de plaquetas <150x109 / L (OR 11,7; IC del 95%: 1,88-75,22; P = 0,009) se asociaron significativamente con SIMS. La presencia de una enfermedad subyacente pareció reducir el riesgo de SIMS (OR 0,06; IC del 95%: 0,01-0,3). Conclusión: El SIMS fue más común en pacientes mayores de 2 años y en aquellos con linfopenia o trombocitopenia. La enfermedad subyacente parece reducir el riesgo del mismo. (AU)

Introduction: SARS-CoV-2-associated pediatric multisystemic inflammatory syndrome (PMIS) is an acute disease accompanied by a hyperinflammatory syndrome, with multiorgan failure and shock associated with SARS CoV2 infection, producing high morbidity in the pediatric population, which so far is affected by this syndrome. Objective: To evaluate the differential characteristics of SARS-COV-2-associated PMIS in children. Methods: A retrospective cohort study was conducted. The definition of PMIS was based on WHO criteria. Patients with temporally related COVID-19 were included as controls. Results: 25 patients with PMIS and 75 controls were included. A multiple logistic regression model of the variables shown to be significant in univariate analysis revealed that age ≥ 2 years (OR 24.7; 95% CI: 1.03 -592.4; P = 0.048), lymphopenia (OR 9.03; 95% CI 2.05-39.7; P = 0.004), and platelet count < 150x109/L (OR 11.7; 95% CI: 1.88-75.22; P = 0.009) were significantly associated with PMIS. The presence of an underlying disease appeared to reduce the risk of PMIS (OR 0.06; 95% CI: 0.01-0.3). Conclusion: PMIS was more common in patients older than 2 years and in those with lymphopenia or thrombocytopenia. Underlying disease appears to reduce the risk of SMIS.(AU)

Manifestaciones Extra pulmonares de la infección por SARS-CoV-2 en Pediatría. Revisión / Extra Pulmonary Manifestations of SARS-CoV-2 Infection in Pediatrics. Review

Las manifestaciones clínicas del SARS-Cov-2 en niños difieren a la de los adultos, con afección respiratoria, gastrointestinal, dermatológica y/o cardiovascular. La mayoría de los niños son asintomáticos o presentan síntomas leves de la infección por COVID-19. Sin embargo, en los últimos meses se ha identificado un pequeño número de niños que desarrollan respuesta inflamatoria sistémica significativa. A continuación, realizamos una revisión sobre las manifestaciones extrapulmonares del SARS-Cov-2

The clinical manifestations of SARS-Cov-2 in children differ from that of adults, with respiratory, gastrointestinal, dermatological and / or cardiovascular conditions. Most children are asymptomatic or have mild symptoms of COVID-19 infection. However, in recent months, a small number of children have been identified who develop a significant systemic inflammatory response. We review the extrapulmonary manifestations of SARS-Cov-2

Síndrome inflamatorio multisistémico en niños asociado al SARS-CoV-2

RESUMEN En general la afectación del Covid 19 en niños es leve o asintomática. Un porcentaje pequeño de pacientes requirieron ingreso a la Unidad de cuidados intensivos pediátricos. Se reporta el caso de un paciente pediátrico hospitalizado en Unidad de Cuidados Intensivos de un hospital pediátrico, en el contexto de la pandemia SARS-CoV-2, que requirió ingreso a la UCI por presentar un shock tóxico, con marcadores inflamatorios, reactantes de fase aguda elevados y manifestaciones clínicas que corresponden al Síndrome Inflamatorio Multisistémico descripto recientemente y relacionado a la infección por COVID-19.

ABSTRACT In general, Covid 19 infection in children is mild or asymptomatic. A small percentage of patients require admission to the Pediatric Intensive Care Unit. We report the case of a pediatric patient hospitalized in the Intensive Care Unit of a pediatric hospital, in the context of the SARS-CoV-2 pandemic, who required admission to the ICU due to toxic shock, with elevation of inflammatory markers and acute phase reactants, along with clinical manifestations that corresponded to the recently described Multisystemic Inflammatory Syndrome related to COVID-19 infection.

Síndrome CINCA: um diagnóstico diferencial da artrite idiopática juvenil / CINCA syndrome: a differential diagnosis of the juvenile idiopathic arthritis

A síndrome CINCA (crônico-infantil-neurológica-cutâneaarticular) é uma enfermidade inflamatória multissistêmica rara, de início no período neonatal e caracterizada por febre, exantema cutâneo, envolvimento articular e do sistema nervoso central. É também conhecida pela literatura médica norte-americana como NOMID (doença multissistêmica inflamatória de início neonatal). Relatamos o caso de uma criança de 3 anos de idade admitida em nosso serviço com história de febre e exantema cutâneo desde o período neonatal. Apresentou crises convulsivas no sexto mês de vida e artrite simétrica de joelhos desde o nono mês. Na admissão, mostrava-se toxemiada, pálida, com um exantema maculopapular generalizado e artrite de joelhos e tornozelos. Apresentava ainda retardo de crescimento e desenvolvimento. Achados laboratoriais incluíram anemia, leucocitose, trombocitose, níveis elevados de proteína C reativa e meningite asséptica no exame do liquor. Os outros exames foram negativos. Os achados radiográficos dos joelhos, quadris e tornozelos foram anormais. A criança recebeu tratamento com antiinflamatório não hormonal, corticosteróide e metotrexato, com melhora apenas da dor e da febre. A etiologia da síndrome CINCA permanece desconhecida e nenhum tratamento tem se mostrado eficaz. Essa doença deve ser distinguida da forma sistêmica da artrite idiopática juvenil (AIJ), o principal diagnóstico diferencial.

CINCA syndrome (chronic-infantile-neurological-cutaneousarticular) is a rare multisystemic inflammatory disease with neonatal onset characterized by fever, skin rash, articular, and central nervous system involvement. This syndrome is known in the North American medical literature as infantile onset multisystem inflammatory disease (NOMID). We describe the case of a 3-yearold child admitted in our service with fever and skin rash since the neonatal period. She presented seizures at 6 months-old and bilateral arthritis of the knees since her 9 months. On admission she looked sick, pale and presented generalized erythematosus maculopapular rash, arthritis of the knees and ankles. She presented growth and mental retardation too. Laboratory Endings included anemia, leukocytosis, thrombocytosis, elevated C-reactive protein levels and the examination Endings from the cerebrospinal fluid showed an aseptic meningitis. Other test results were negative. Radiographs of the knees, hips and ankles revealed abonrmalities. The child received treatment with nonsteroidal anti-inflammatory drugs, corticosteroids and methotrexate, with partial response to treatment, leading to improvement in pain and fever defervescence. The etiology of CINCA syndrome remains unknown and no single treatment has been found to be effective. This disease should be distinguished from systemic onset juvenile idiophatic arthritis (JIA), the main differential diagnosis.