Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

Association of Cancer Diagnosis and Therapeutic Stage With Mortality in Pediatric Patients With COVID-19, Prospective Multicenter Cohort Study From Latin America.

Background: Children with cancer are at risk of critical disease and mortality from COVID-19 infection. In this study, we describe the clinical characteristics of pediatric patients with cancer and COVID-19 from multiple Latin American centers and risk factors associated with mortality in this population. Methods: This study is a multicenter, prospective cohort study conducted at 12 hospitals from 6 Latin American countries (Argentina, Bolivia, Colombia, Ecuador, Honduras and Peru) from April to November 2021. Patients younger than 14 years of age that had an oncological diagnosis and COVID-19 or multisystemic inflammatory syndrome in children (MIS-C) who were treated in the inpatient setting were included. The primary exposure was the diagnosis and treatment status, and the primary outcome was mortality. We defined "new diagnosis" as patients with no previous diagnosis of cancer, "established diagnosis" as patients with cancer and ongoing treatment and "relapse" as patients with cancer and ongoing treatment that had a prior cancer-free period. A frequentist analysis was performed including a multivariate logistic regression for mortality. Results: Two hundred and ten patients were included in the study; 30 (14%) died during the study period and 67% of patients who died were admitted to critical care. Demographics were similar in survivors and non-survivors. Patients with low weight for age (<-2SD) had higher mortality (28 vs. 3%, p = 0.019). There was statistically significant difference of mortality between patients with new diagnosis (36.7%), established diagnosis (1.4%) and relapse (60%), (p <0.001). Most patients had hematological cancers (69%) and they had higher mortality (18%) compared to solid tumors (6%, p= 0.032). Patients with concomitant bacterial infections had higher mortality (40%, p = 0.001). MIS-C, respiratory distress, cardiovascular symptoms, altered mental status and acute kidney injury on admission were associated with higher mortality. Acidosis, hypoxemia, lymphocytosis, severe neutropenia, anemia and thrombocytopenia on admission were also associated with mortality. A multivariate logistic regression showed risk factors associated with mortality: concomitant bacterial infection OR 3 95%CI (1.1-8.5), respiratory symptoms OR 5.7 95%CI (1.7-19.4), cardiovascular OR 5.2 95%CI (1.2-14.2), new cancer diagnosis OR 12 95%CI (1.3-102) and relapse OR 25 95%CI (2.9-214). Conclusion: Our study shows that pediatric patients with new onset diagnosis of cancer and patients with relapse have higher odds of all-cause mortality in the setting of COVID-19. This information would help develop an early identification of patients with cancer and COVID-19 with higher risk of mortality.

Difficult acute lymphoblastic leukaemia diagnosis in a paediatric patient with mixed presentation of COVID-19 acute respiratory failure and multisystemic inflammatory syndrome.

New diagnoses of leukaemia and other malignancies are recently being made in paediatric patients with COVID-19. The rates of mortality and morbidity in some of these children are expected to be higher. In new cases, concurrent diagnosis can be difficult because multisystemic inflammatory syndrome (MIS-C) and malignancies have similar clinical presentations. We present the case of a preteenage child where the diagnosis of leukaemia was complicated and delayed by a multisystem involvement and an inconclusive bone marrow study. Clinical teams managing children with COVID-19 and MIS-C should suspect leukaemia and other malignancies when the clinical course is complicated and bone marrow suppression is persistent. Prompt diagnosis will allow start of treatment on time, minimising complications.

Systemic lupus erythematosus complicated with macrophage activation syndrome mimicking COVID-19 multisystemic inflammatory syndrome in children.

BACKGROUND: Macrophage activation syndrome (MAS) is characterized by excessive activation of macrophages and lymphocytes, leading to multiorgan dysfunction. As the initial manifestation of systemic lupus erythematosus (SLE), MAS is rare in children. Due to the COVID-19 pandemic, it is vital to identify the MAS as it shares similar characteristics with the multisystem inflammatory syndrome in children (MIS-C). CASE REPORT: We report the case of an 11-year-old male adolescent with symptoms of MIS-C. Although with negative results of RT-PCR (reverse transcription-polymerase chain reaction) and serology for SARS-CoV-2, contact with a positive COVID-19 relative was reported. When admitted to a referral hospital center, the patient received standard treatment for MIS-C. Although the same scheme was given on three occasions, the patient showed no response to initial therapy. Thus, the patient was classified as a refractory case. When the study was extended to other differential diagnoses, we found MAS associated with SLE. Therefore, the patient was treated with etoposide, cyclosporine, dexamethasone, and methotrexate and showed a good clinical response. CONCLUSIONS: MAS associated with SLE is rare in the pediatric population. MAS shares inflammatory markers with the MIS-C and is often confused with rheumatologic, infectious, and neoplastic entities. Reporting this case is important to identify differential diagnoses in patients presenting as MIS-C and decide on timely treatment, as it could be harmful or even fatal if a definitive diagnosis is not obtained on time.

INTRODUCCIÓN: El síndrome de activación de macrófagos (SAM) se caracteriza por una activación excesiva de los macrófagos y de los linfocitos que conduce a una disfunción multiorgánica. Como manifestación inicial del lupus eritematoso sistémico (LES), el SAM es poco común en la infancia. Debido a la pandemia de COVID-19, es importante identificar el SAM, ya que comparte características similares con el síndrome inflamatorio multisistémico en niños (MIS-C, por sus siglas en inglés). CASO CLÍNICO: Presentamos el caso de un varón de 11 años con síntomas de MIS-C. Resultó negativo en la prueba de reacción en cadena de la polimerasa con retrotranscriptasa y en la serología para SARS-CoV-2, aunque reportó contacto con un familiar positivo para COVID-19. Ingresó en un centro hospitalario de referencia y recibió tratamiento estandarizado para MIS-C. A pesar de recibir el mismo esquema en tres ocasiones, no mostró respuesta a la terapia inicial, por lo que fue clasificado como caso refractario. Al ampliar el estudio para otros diferenciales, se encontró SAM asociado con LES, por lo que el paciente recibió tratamiento con etopósido, ciclosporina, dexametasona y metotrexato, y mostró buena respuesta clínica. CONCLUSIONES: La asociación entre el SAM y el LES es rara en la población pediátrica. El SAM comparte marcadores inflamatorios con el MIS-C y suele confundirse con enfermedades reumatológicas, infecciosas y neoplásicas. La importancia de reportar este caso es identificar los diagnósticos diferenciales en los pacientes que se presentan como MIS-C, y decidir el tratamiento con prontitud, pues podría ser dañino o incluso fatal si no se obtiene un diagnóstico definitivo a tiempo.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Severe diabetic ketoacidosis precipitated by COVID-19 in pediatric patients: Two case reports. / Cetoacidosis diabética severa precipitada por COVID-19 en pacientes pediátricos: reporte de dos casos.

INTRODUCTION: The association of COVID-19 with diabetes mellitus is bidirectional. In one direction, diabetes mellitus is associated with an increased risk of severe COVID-19. In the opposite direction, in patients with COVID-19 new-onset diabetes mellitus, severe diabetic ketoacidosis and severe metabolic complications have been described. CLINICAL CASE: This report describes two patients with diabetes mellitus who came to our hospital with ketoacidosis resulting from new-onset diabetes mellitus. We describe the clinical course and the management approach during the COVID-19 pandemic. CONCLUSION: COVID-19 is associated with metabolic complications such as severe diabetic ketoacidosis.

INTRODUCCIÓN: La relación entre la enfermedad por el coronavirus de 2019 (COVID-19) secundaria a SARS-CoV-2 y la diabetes mellitus es bidireccional. Por un lado, la diabetes mellitus se asocia con un mayor riesgo de COVID-19 grave. Por otro lado, en pacientes con COVID-19 se han observado diabetes mellitus de nueva aparición con presentaciones de cetoacidosis diabética y complicaciones metabólicas graves de dicha presentación. CASOS CLÍNICOS: En este informe, describimos a dos pacientes pediátricos con diabetes mellitus que acudieron a nuestro hospital con cetoacidosis diabética, de debut inicial. Describimos la evolución y el manejo clínico y terapéutico durante la pandemia de COVID-19. CONCLUSIÓN: La infección por COVID-19 puede precipitar complicaciones como cetoacidosis diabética severa.

High incidence of stroke and mortality in pediatric critical care patients with COVID-19 in Peru.

INTRODUCTION: Pediatric critical care patients with COVID-19 treated in Peru have higher mortality than those previously reported from other countries. Pediatric providers have reported a high number of patients without comorbidities presenting with hemorrhagic strokes associated with COVID-19. We present a study analyzing the factors associated with mortality in this setting. METHODS: Prospective case-control study that included patients <17 years old admitted to a pediatric critical care unit with a positive test confirming COVID-19. The primary outcome was mortality. Fisher's exact test and the Mann-Whitney U test were used for the analysis. RESULTS: Forty-seven patients were admitted to critical care. The mortality of our study is 21.3%. The mortality of patients with neurological presentation was 45.5%, which was significantly higher than the mortality of acute COVID-19 (26.7%) and MIS-C (4.8%), p 0.18. Other risk factors for mortality in our cohort were strokes and comorbidities. Only one patient presenting with hemorrhagic stroke had an undiagnosed comorbidity. CONCLUSION: Cerebrovascular events associated with COVID-19 in pediatric patients, including infants, must be recognized as one of the more severe presentations of this infection in pediatric patients. IMPACT: Pediatric patients with COVID-19 can present with hemorrhagic and ischemic strokes on presentation. Neurological presentation in pediatric patients with COVID-19 has high mortality. Mortality of pediatric patients with COVID-19 is associated with comorbidities. Pediatric presentation and outcomes of COVID-19 in different regions can be novel to previously described.

[Cross-sectional study of the clinical characteristics and outcomes of children hospitalized with COVID-19 in Lima, Peru]. / Estudio transversal analítico de las características y desenlaces clínicos de niños hospitalizados con COVID-19 en Lima, Perú.

INTRODUCTION: Coronavirus 2019 (SARS-CoV-2) infection in children occurred in Peru as of March 2020, leading to pediatric patients' hospitalization in areas adapted for this purpose at the Edgardo Rebagliati Martins National Hospital. In the beginning, the demand for hospitalization was low, but it increased gradually. Consistent with international reports, the majority of patients presented mild or moderate symptoms. Nonetheless, there were also severe cases, even fatal ones. OBJECTIVES: To describe the characteristics and clinical outcome of pediatric patients with COVID-19 hospitalized in a referral hospital in Lima, Peru, between March and August 2020. METHODS: A descriptive and inferential cross-sectional study was carried out. The population includes all hospitalized patients in the Department of Pediatrics, with clinical and surgical diagnoses associated with COVID-19. RESULTS: We included 100 patients, with an average age of 83.4 ± 54 months, with a predominance of male patients (55%). Hospitalized patients were grouped into five categories: respiratory failure (17%), multisystemic inflammatory syndrome (MIS-C) (31%), neurological presentation (19%), acute abdomen (20%), and patients with oncological problems (13%). Most of the patients (74%) had comorbidities. Regarding the presenting symptoms, intestinal pain predominated in the appendicitis group (90%, p < 0.001), fever was present in most patients with respiratory failure (64.7%); multisystemic inflammatory syndrome (90.3%), neurological manifestations (15.8%), acute abdomen (50%) and oncological conditions (61.5%) were also present in these patients. Kawasaki symptoms were found in 38.7% of the patients with multisystemic inflammatory syndrome. Mortality was 4%. Respiratory problems (29.4%) and multisystemic inflammatory syndrome (22.6%) required admission to intensive care, more frequently than the other presentations (p = 0.008). CONCLUSIONS: We conclude that the vulnerability in the pediatric population is the one that has preexisting conditions. We divided our patients according to presentation, diagnosis, and complications, which were predominantly respiratory. We also had oncological patients with COVID-19.

INTRODUCCIÓN: La infección por coronavirus 2019 (SARS-CoV-2) en niños se presentó en Perú desde marzo del 2020. Desde entonces fue necesario internar pacientes pediátricos en el Hospital Nacional Edgardo Rebagliati Martins, en el área de hospitalización adaptada para dicho propósito. Al inicio, la demanda de hospitalización era baja y se fue incrementando progresivamente. Coincidiendo con los reportes internacionales, la mayoría presentó cuadros leves o moderados, pero también hubo casos graves e incluso mortales. OBJETIVOS: Describir las características y el desenlace clínico de los pacientes pediátricos con COVID-19 hospitalizados en un hospital de referencia en Lima, Perú, entre marzo y agosto de 2020. MÉTODOS: Se realizó un estudio transversal descriptivo e inferencial. La población incluyó a todos los pacientes que se hospitalizaron en el Departamento de Pediatría Clínica, con diagnósticos clínicos y quirúrgicos asociados a COVID-19. RESULTADOS: Incluimos 100 pacientes, con edad promedio de 83,4 ± 54 meses, con predominio de varones (55%). Los pacientes hospitalizados fueron agrupados en cinco categorías: insuficiencia respiratoria (17%), síndrome inflamatorio multisistémico (31%), presentación neurológica (19%), abdomen agudo (20%) y pacientes con problemas oncológicos (13%). La mayoría de los pacientes (74%) tenían comorbilidades. Respecto a los síntomas de presentación, el dolor intestinal predominó en el grupo de apendicitis (90%, p < 0,001), la fiebre estuvo presente en la mayoría de los pacientes con falla respiratoria (64,7%), el síndrome inflamatorio multisistémico se registró en 90,3%, la sintomatología neurológica en 15,8%, el abdomen agudo 50% y oncológicos en 61,5% de los pacientes. Los síntomas de Kawasaki estuvieron presentes en 38,7% de los pacientes con síndrome inflamatorio multisistémico. La mortalidad fue de 4%. En 29,4% de problemas respiratorios y en 22,6% de síndrome inflamatorio multisistémico, se requirió de admisión en cuidados intensivos, lo que fue más frecuente que las otras presentaciones (p = 0,008). CONCLUSIONES: Se concluye que la población pediátrica vulnerable es aquella con comorbilidades preexistentes. La división de pacientes en nuestro estudio fue definida por la presentación, diagnóstico y complicaciones predominantemente con problemas respiratorios, y en pacientes oncológicos con COVID-19.