Paediatric critical COVID-19 and mortality in a multinational prospective cohort.

Background: To understand critical paediatric coronavirus disease 2019 (COVID-19) and evaluate factors associated with mortality in children from high and low-middle income countries. Methods: Prospective, observational study of critically ill children hospitalised for COVID-19 in 18 countries throughout North America, Latin America, and Europe between April 1 and December 31, 2020. Associations with mortality were evaluated using logistic regression. Findings: 557 patients (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Invasive (41%) or non-invasive (20%) ventilation and vasopressors (56%) were the most common support modalities. Hospital mortality was 10% and higher in children <2 years old (15%; odds ratio 1·94, 95%CI 1·08-3·49). Most who died had pulmonary disease. When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2·89; 95%CI 1·2-6·94) or pulmonary comorbidities (aOR 4·43; 95%CI 1·70-11·5), admission hypoxemia (aOR 2·44; 95%CI 1·30-4·57), and lower respiratory symptoms (aOR 2·96; 95%CI 1·57-5·59). MIS-C (aOR 0·25; 95%CI 0·1-0·61) and receiving methylprednisolone (aOR 0·5; 95%CI 0·25-0·99), IVIG (aOR 0·32; 95%CI 0·16-0·62), or anticoagulation (aOR 0·49; 95%CI 0·25-0·95) were associated with lower mortality although these associations might be limited to children >2 years old. Interpretation: We identified factors associated with COVID-19 mortality in critically ill children from both high and low-middle income countries, including higher mortality with younger age and COVID-related pulmonary disease but lower mortality in MIS-C. Further research is needed on optimal treatments for younger children and respiratory failure in paediatric COVID-19. Funding: None.

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.

Comparison of Interleukin-6 Plasma Concentration in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Pediatric Sepsis.

Importance: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy. Objective: To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis. Design: A retrospective cohort study from previously collected data. Setting: Individual patient data were gathered from three different international datasets. Participants: Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy. Exposure: None. Main Outcome(s) and Measure(s): The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done. Results: We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis (p < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock. Conclusions and Relevance: IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.

Persistent COVID-19 lung infection in a child with a primary immunodeficiency.

SARS-CoV-2 infection in children with primary immunodeficiency disease (PID) and its complications have not yet been well described, the course of COVID-19 can range from mild illness to death. We aim to report the case of a child with a PID who develop a severe and persistent pulmonary COVID-19 infection. We present chronologically his clinical course, tests, interventions and radiological findings showing his irregular evolution and poor response to infection. This case highlights the need to accurately monitor the immune response in these cases to try to stop the progression of the damage.

Reduced PICU respiratory admissions during COVID-19.

BACKGROUND: The COVID-19 pandemic reached the Southern Hemisphere in the autumn of 2020, thus coinciding with its expected annual viral respiratory season. The potential impact of national strategies aimed at mitigating COVID-19 during the pandemic on the incidence of other critical viral lower respiratory tract infections (LRTIs) in children is unknown. METHODS: We analysed admission data for LRTIs from 22 paediatric intensive care units (PICUs) in four countries, part of a large international Latin American registry of children with acute respiratory failure (Red Colaborativa Pediátrica de Latinoamérica [LARed Network]). RESULTS: Between January and August, there were 83% fewer PICU admissions for LRTIs in 2020 compared to the 2018/2019 average over the same period. Similar decreases were noted for PICU admissions due to respiratory syncytial virus and influenza (92% and 78%, respectively). CONCLUSION: We observed a striking reduction in PICU admissions due to viral LRTIs over winter, during the COVID-19 pandemic in South America.

Recommendations for the initial management of multisystem inflammatory syndrome temporally related to COVID-19, in children and adolescents

El síndrome inflamatorio multisistémico en niños y adolescentes temporalmente relacionado con COVID-19 es una presentación clínica de la infección por SARS-CoV-2. Comparte algunas características con la enfermedad de Kawasaki, el shock tóxico, la sepsis, el síndrome de activación macrofágica y la miocarditis. Son escasas las publicaciones que abordan su manejo inicial, que tiene semejanzas con el propuesto para el shock séptico. Esta revisión analiza dicho abordaje basado en las características propias del síndrome inflamatorio multisistémico relacionado con COVID-19, de acuerdo con el paradigma de construcción de una "guía de práctica institucional", y sugiere estrategias de aproximación terapéutica, que incluyen detección temprana, estabilización, referencia, tratamiento específico y análisis de proceso Multisystem inflammatory syndrome temporally related to COVID-19 in children and adolescents is a clinical presentation of SARS-CoV-2 infection. It shares some features with Kawasaki disease, toxic shock, sepsis, macrophage activation syndrome, and myocarditis. Few publications have addressed its initial management, which is similar to that proposed for septic shock. This review analyzes such approach based on the characteristics typical of multisystem inflammatory syndrome related to COVID-19 in accordance with the paradigm of an "institutional practice guideline"and suggests therapeutic approach strategies, including early detection, stabilization, referral, specific treatment, and process analysis.

Pediatric Inflammatory Multisystem Syndrome Associated With SARS-CoV-2: A Case Series Quantitative Systematic Review.

ABSTRACT: Pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) is infrequent, but children might present as a life-threatening disease. In a systematic quantitative review, we analyzed 11 studies of PIMS-TS, including 468 children reported before July 1, 2020. We found a myriad of clinical features, but we were able to describe common characteristics: previously healthy school-aged children, persistent fever and gastrointestinal symptoms, lymphopenia, and high inflammatory markers. Clinical syndromes such as myocarditis and Kawasaki disease were present in only one third of cases each one. Pediatric intensive care unit admission was frequent, although length of stay was less than 1 week, and mortality was low. Most patients received immunoglobulin or steroids, although the level of evidence for that treatment is low. The PIMS-ST was recently described, and the detailed quantitative pooled data will increase clinicians' awareness, improve diagnosis, and promptly start treatment. This analysis also highlights the necessity of future collaborative studies, given the heterogeneous nature of the PIMS-TS.

Recommendations for the initial management of multisystem inflammatory syndrome temporally related to COVID-19, in children and adolescents. / Recomendaciones para el manejo inicial del síndrome inflamatorio multisistémico relacionado temporalmente con COVID-19, en niños y adolescentes.

Multisystem inflammatory syndrome temporally related to COVID-19 in children and adolescents is a clinical presentation of SARS-CoV-2 infection. It shares some features with Kawasaki disease, toxic shock, sepsis, macrophage activation syndrome, and myocarditis. Few publications have addressed its initial management, which is similar to that proposed for septic shock. This review analyzes such approach based on the characteristics typical of multisystem inflammatory syndrome related to COVID-19 in accordance with the paradigm of an "institutional practice guideline" and suggests therapeutic approach strategies, including early detection, stabilization, referral, specific treatment, and process analysis.

El síndrome inflamatorio multisistémico en niños y adolescentes temporalmente relacionado con COVID-19 es una presentación clínica de la infección por SARS-CoV-2. Comparte algunas características con la enfermedad de Kawasaki, el shock tóxico, la sepsis, el síndrome de activación macrofágica y la miocarditis. Son escasas las publicaciones que abordan su manejo inicial, que tiene semejanzas con el propuesto para el shock séptico. Esta revisión analiza dicho abordaje basado en las características propias del síndrome inflamatorio multisistémico relacionado con COVID-19, de acuerdo con el paradigma de construcción de una "guía de práctica institucional", y sugiere estrategias de aproximación terapéutica, que incluyen detección temprana, estabilización, referencia, tratamiento específico y análisis de procesos.