[Hyperinflammatory immune response syndrome PIMS-TS]. / «Nachwehen¼: Hyperinflammatorisches Immunreaktionssyndrom PIMS-TS.

INTRODUCTION: PIMS-TS is a rare hyperinflammatory immune response syndrome, usually occurring two to six weeks after SARS-CoV-2 infection, which mainly affects schoolchildren and is often associated with the need for intensive care (2). The most common clinical signs are high fever, gastrointestinal symptoms such as abdominal pain, vomiting and diarrhea, cardiovascular dysfunction (impaired LVEF, hypotension, shock) and neurological symptoms such as headache and encephalopathy (1, 2, 4). The definition criteria include various clinical and laboratory parameters, which vary slightly depending on the authors (4, 6, 7). With intensive care treatment with circulatory support and administration of methylprednisolone, mortality and long-term consequences remain low.

Elevated risk for psychiatric outcomes in pediatric patients with Multisystem Inflammatory Syndrome (MIS-C): A review of neuroinflammatory and psychosocial stressors.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a secondary immune manifestation of COVID-19 involving multiple organ systems in the body, resulting in fever, skin rash, abdominal pain, nausea, shock, and cardiac dysfunction that often lead to hospitalization. Although many of these symptoms resolve following anti-inflammatory treatment, the long-term neurological and psychiatric sequelae of MIS-C are unknown. In this review, we will summarize two domains of the MIS-C disease course, 1) Neuroinflammation in the MIS-C brain and 2) Psychosocial disruptions resulting from stress and hospitalization. In both domains, we present existing clinical findings and hypothesize potential connections to psychiatric outcomes. This is the first review to conceptualize a holistic framework of psychiatric risk in MIS-C patients that includes neuroinflammatory and psychosocial risk factors. As cases of severe COVID-19 and MIS-C subside, it is important for clinicians to monitor outcomes in this vulnerable patient population.

Anti-SARS-CoV-2 Vaccination and PIMS-TS-Friends or Foe? Case Reports and Literature Review.

Pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), also known as a multisystem inflammatory syndrome in children (MIS-C), is diagnosed in children who develop an inadequate inflammatory response after exposure to the SARS-CoV-2 virus. The pathogenesis of the abnormal response of the immune system to a previous SARS-COV-2 infection has not been explained. Similarly, the safety and effectiveness of COVID-19 vaccinations in this group of patients have become the subject of clinical discussion. Presenting experiences from many centers aims to answer this question. We present 4 cases of patients who suffered from PIMS-TS. Three of them were safely vaccinated against COVID-19 after illness. One patient developed PIMS-TS temporarily associated with COVID-19 vaccination. We also collected and discussed data from other centers.

Comparación de biomarcadores inflamatorios plasmáticos en pacientes con SIM-PedS versus infecciones potencialmente graves en pacientes pediátricos / Comparison of plasma inflammatory biomarkers between MIS-C and potentially serious infections in pediatric patients

Introducción: Los biomarcadores inflamatorios se han utilizado para el diagnóstico y tratamiento del síndrome inflamatorio multisistémico en niños (SIM-PedS). Nuestro objetivo fue determinar cómo se comportan estos biomarcadores inflamatorios en pacientes con síndrome febril orientados en principio como infección bacteriana potencialmente grave y comparar los hallazgos clínicos y de laboratorio con los casos SIM-PedS. Métodos: Estudio de cohorte observacional ambispectivo unicéntrico (junio de 2020-febrero de 2022). Analizamos la demografía, los síntomas clínicos y los hallazgos de laboratorio en casos SIM-PedS y en casos de síndrome febril de otras etiologías infecciosas de pacientes menores de 15 años con ingreso hospitalario. Resultados: Incluimos a 54 pacientes con sospecha analítica de infección bacteriana y a 20 pacientes con SIM-PedS para el análisis. La fiebre (100%), los hallazgos gastrointestinales (80%) y mucocutáneos (35%) fueron más frecuentes en los pacientes con SIM-PedS, también la hipotensión (36,8%) y la taquicardia (55%). Los hallazgos de laboratorio mostraron niveles significativamente elevados de pro-BNP (70%), ferritina (35%), dímeros D (80%) así como linfopenia (55%) y trombocitopenia (27,8%) en los casos de SIM-PedS. Los valores de IL-6 fueron elevados en pacientes sin SIM-PedS (92,6%). Conclusiones: En el manejo de pacientes con SIM-PedS, la monitorización dinámica de pro-BNP, ferritina, dímero D, linfocitos y plaquetas podría ser útil para evaluar efectivamente el progreso de la enfermedad en las primeras fases. Los valores de IL-6 pueden elevarse de forma significativa en pacientes con síndrome febril de otras etiologías, así como los dímeros D. El uso de diversos biomarcadores de laboratorio podría ayudar a determinar precozmente la evolución de los pacientes con síndrome febril.(AU)

Background: Inflammatory biomarkers have been used for the diagnosis and management of multisystemic inflammatory syndrome in children (MIS-C). We aimed to compare the clinical and laboratory findings of MIS-C cases versus other febrile cases cataloged as potentially suspected bacterial infection (non-MIS-C). Methods: Unicentric ambispective observational cohort study (June 2020 to February 2022). We analyzed demographics, clinical symptoms and laboratory findings in MIS-C cases and in non-MIS-C cases with febrile processes of patients under 15 years of age admitted to hospital. Results: We enrolled 54 patients with potential suspected bacterial infection and 20 patients with MIS-C for analysis. Fever (100%), gastrointestinal (80%) and mucocutaneous findings (35%) were common in MIS-C patients, also hypotension (36.8%) and tachycardia (55%). Laboratory findings showed significantly elevated proBNP (70%), ferritin (35%), D-dimer (80%) and lymphopenia (55%) and thrombocytopenia (27.8%) in MIS-C cases. IL-6 values were high in non-MIS-C patients (92.6%). Conclusions: In the management of MIS-C patients, the dynamic monitoring of proBNP, ferritin, D-dimer, lymphocytes and platelets could be helpful to pediatricians to effectively evaluate the progress of MIS-C in the early phases, not IL-6 values. The applicability of the IL-6 level as a prognostic biomarker in MIS-C patients may require closer discussion. In addition, the optimal laboratory markers, as stated in our study, can help establish a biomarkers model to early distinguish the MIS-C versus non-MIS-C in patients who are admitted to febrile syndrome.(AU)

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.

Comparison of plasma inflammatory biomarkers between MIS-C and potentially serious infections in pediatric patients.

BACKGROUND: Inflammatory biomarkers have been used for the diagnosis and management of multisystemic inflammatory syndrome in children (MIS-C). We aimed to compare the clinical and laboratory findings of MIS-C cases versus other febrile cases cataloged as potentially suspected bacterial infection (non-MIS-C). METHODS: Unicentric ambispective observational cohort study (June 2020-February 2022). We analyzed demographics, clinical symptoms and laboratory findings in MIS-C cases and in non-MIS-C cases with febrile processes of patients under 15 years of age admitted to hospital. RESULTS: We enrolled 54 patients with potential suspected bacterial infection and 20 patients with MIS-C for analysis. Fever (100%), gastrointestinal (80%) and mucocutaneous findings (35%) were common in MIS-C patients, also hypotension (36.8%) and tachycardia (55%). Laboratory findings showed significantly elevated proBNP (70%), ferritin (35%), D-dimer (80%) and lymphopenia (55%) and thrombocytopenia (27.8%) in MIS-C cases. IL-6 values were high in non-MIS-C patients (92.6%). CONCLUSIONS: In the management of MIS-C patients, the dynamic monitoring of proBNP, ferritin, D-dimer, lymphocytes and platelets could be helpful to pediatricians to effectively evaluate the progress of MIS-C in the early phases, not IL-6 values. The applicability of the IL-6 level as a prognostic biomarker in MIS-C patients may require closer discussion. In addition, the optimal laboratory markers, as stated in our study, can help establish a biomarkers model to early distinguish the MIS-C versus non-MIS-C in patients who are admitted to febrile syndrome.

Characteristics and Outcomes of Children With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Admitted to a Quaternary Hospital: A Single-Center Experience.

Objectives In the setting of the recent global pandemic, children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) presented to our hospital with a variety of symptoms ranging from mild to severe disease including multiorgan dysfunction. Our objective was to study the clinical profile, risk factors, complications, and outcomes in pediatric patients admitted to our center with SARS-CoV-2 infection. Methods This retrospective observational study was conducted at a large quaternary center in Riyadh between May 2020 and September 2021. The study population was comprised of children between 0 and ≤14 years with SARS-CoV-2 suspicion or positivity. Results One hundred and fifty-six children were included in the study, the majority of whom were 1-10 years old. One hundred and twenty of them (76.93%) were SARS-CoV-2 positive. Fifty-nine patients (37.18%) were labelled as multisystem inflammatory syndrome in children (MIS-C) based on clinical and lab criteria, of whom 35 (22.44%) tested SARS-CoV-2 positive. Hematological disease was found to be the most common comorbidity, followed by neurological and chronic lung diseases. The most common symptoms encountered were fever, cough, vomiting, fatigue, and diarrhea. Eighty patients (51%) required pediatric intensive care unit (PICU) admission (length of stay: 5-12 days), among whom 32 (40%) required ventilation, 26 (32.5%) needed hemodynamic support, and three patients (3.75%) underwent continuous renal replacement therapy (CRRT). The overall mortality rate was 4.5% (seven patients) among the studied population. The most frequent lab abnormalities were found to be elevated serum ferritin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels. Ninety-one percent received antibiotics, and prophylactic anticoagulant was used in 32%. In the MIS-C subset, 80.5% received steroids, 71.43% intravenous immunoglobulin (IVIG), and 5.17% (three patients) tocilizumab. Conclusion The SARS-CoV-2 infection presented with a range of severity among our cohort of children; however, most of the patients responded well to appropriate supportive treatment. A slight male preponderance was noted. The most common symptoms encountered were fever, cough, vomiting, fatigue, and diarrhea. Inflammatory markers such as ESR, CRP, serum ferritin, and LDH levels were found to be elevated in nearly all patients. Raised serum lactate and serum creatinine and lymphopenia were of significant note in patients with MIS-C. Higher mortality rates were observed in patients with MIS-C and those requiring respiratory support. In addition to these two factors, the presence of comorbidities and the need for CRRT were associated with prolonged PICU length of stay.

Vaccination against COVID-19 - risks and benefits in children.

Countries in Europe and around the world have taken varying approaches to their policies on COVID-19 vaccination for children. The low risk of severe illness from COVID-19 means that even small risks from vaccination warrant careful consideration. Vaccination appears to result in a decreased risk of severe illness including the paediatric multi-system inflammatory syndrome known to be associated with COVID-19. These risks have already decreased significantly with the emergence of the Omicron variant and its subvariants, and due to widespread population immunity through previous infection. There is a relatively high risk of myocarditis following second doses of mRNA vaccines in adolescent males, although the general course of this condition appears mild.   Conclusion: COVID-19 vaccination only provides a transient reduction in transmission. Currently, insufficient evidence exists to determine the impact of vaccination on post-acute COVID syndromes in children, which are uncommon. What is Known: • Vaccines against COVID-19 have significantly reduced morbidity and mortality around the world. • Whilst countries have universally recommended vaccines for adults and continue to recommend them for vulnerable populations, there has been more variability in recommendations for children. What is New: • In the setting of near universal existing immunity from infection, the majority of the initial benefit in protecting against severe illness has been eroded. • The risks of myocarditis following mRNA vaccination for children is low, but an important consideration given the modest benefits.

Short-term and medium-term clinical outcomes of multisystem inflammatory syndrome in children: a prospective observational cohort study.

BACKGROUND: Even though the incidence of Multisystem Inflammatory Syndrome in children (MIS-C) is decreasing cases are still reported across the world. Studying the consequences of MIS-C enhances our understanding of the disease's prognosis. The objective of this study was to assess short- and medium-term clinical outcomes of MIS-C. METHODS: Prospective observational cohort study at Municipal Children's Hospital Morozovskaya, Moscow, Russia. All children meeting the Royal College of Paediatrics and Child Health (RCPCH), Centers for Disease Control and Prevention (CDC), or the World Health Organization (WHO) MIS-C case definition admitted to the hospital between 17 May and 26 October 2020 were included in the study. All survivors were invited to attend a clinic at 2 and 6 weeks after hospital discharge. RESULTS: 37 children median age 6 years (interquartile range [IQR] 3.3-9.4), 59.5% (22/37) boys were included in the study. 48.6% (18/37) of patients required ICU care. One child died. All children had increased levels of systemic inflammatory markers during the acute event. Echocardiographic investigations identified abnormal findings in 35.1% (13/37) of children. 5.6% (2/36) of children were presenting with any symptoms six weeks after discharge. By six weeks the inflammatory markers were within the reference norms in all children. The echocardiographic evaluation showed persistent coronary dilatation in one child. CONCLUSIONS: Despite the severity of their acute MIS-C, the majority of children in our cohort fully recovered with none having elevated laboratory markers of inflammation at 6 weeks, few (< 10%) reporting persistent symptoms at 6 weeks, and only one with persistent echocardiographic abnormalities.

Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial.

Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39). Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. Funding: NOMIS, Vontobel, and Gaydoul Foundation.

Prognostic factors for multisystem inflammatory syndrome in children: A systematic review and meta-analysis.

AIM: Multisystem inflammatory syndrome in children (MIS-C) is a novel condition that can occur post-SARS-CoV-2 infection in children and adolescents. There is a paucity of evidence on the prognostic factors associated with MIS-C. The aim of this systematic review and meta-analysis was to summarise the prognostic factors for MIS-C development. METHODS: Five databases were systematically searched from January 2020 to May 2023 for studies reporting on prognostic factors for MIS-C using multivariable regression models. Random-effects meta-analyses were conducted to pool odds ratios for each prognostic factor. Risk of bias was rated using QUIPS and the GRADE framework was used to assess the certainty of evidence for each unique factor. RESULTS: Twelve observational studies (N = 18 024) were included, and 13 unique prognostic factors were amenable to meta-analysis. With moderate certainty, age <12 years, male sex and Black race probably increase the risk of MIS-C. Malignancy and underlying respiratory disease probably decrease the risk of MIS-C. Low-certainty evidence suggests that Asian race may increase the risk of MIS-C, and comorbidity may decrease the risk of MIS-C. CONCLUSION: Current literature presents several prognostic factors related to MIS-C following SARS-CoV-2 infection. Further research is necessary to elucidate the pathophysiologic mechanisms related to MIS-C.

Demographic, clinical and laboratory differences between paediatric acute COVID-19 and PIMS-TS-results from a single centre study in the UK.

Background: Paediatric symptomatic SARS-CoV-2 infections associate with two presentations, acute COVID-19 and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Phenotypic comparisons, and reports on predictive markers for disease courses are sparse and preliminary. Methods: A chart review of COVID-19 and PIMS-TS patients (≤19 years) admitted to Alder Hey Children's NHS Foundation Trust, a tertiary centre in the North-West of England, was performed (02/2020-09/2022). Results: A total of 161 symptomatic COVID-19 and 50 PIMS-TS patients were included. Peaks in admissions of patients with PIMS-TS occurred approximately 4 weeks after those for acute COVID-19. The incidence of in-patients with PIMS-TS reduced over time, and there were no admissions after February 2022. When compared to acute COVID-19, PIMS-TS patients were older (median: 10.3 years vs. 2.03 years; p < 0.001). There were no differences in gender distribution, but minority ethnicities were over-represented among PIMS-TS patients. Regional ethnic distribution was reflected among acute COVID-19 patients (66% vs. 84.5% White Caucasian, p = 0.01). Pre-existing comorbidities were more common among acute COVID-19 patients (54.7% vs. 8%, p < 0.001). PIMS-TS patients more commonly presented with abdominal symptoms (92% vs. 50.3%), neurological symptoms (28% vs. 10.6%) and skin rashes (72% vs. 16.8%), (p ≤ 0.01) when compared with acute COVID-19, where respiratory symptoms were more common (51.6% vs. 32%, p = 0.016). PIMS-TS more frequently required intensive care admission (64% vs. 16.8%), and inotropic support (64% vs. 9.3%) (all p < 0.05). More deaths occurred among acute COVID-19 patients [0 vs. 7 (4.4%)], with 5/7 (71%) in the context of pre-existing comorbidities. When compared to acute COVID-19, PIMS-TS patients exhibited more lymphopenia and thrombocytopenia, a more pronounced acute phase reaction, and more hyponatraemia (p < 0.05). Partial least square discriminant analysis of routine laboratory parameters allowed (incomplete) separation of patients at diagnosis, and variable importance projection (VIP) scoring revealed elevated CRP and low platelets as the most discriminatory parameters. Conclusion: Admissions for PIMS-TS reduced with increasing seroconversion rates in the region. Young age and pre-existing comorbidities associate with hospital admission for acute COVID-19. While PIMS-TS may present more acutely with increased need for intensive care, acute COVID-19 had an increased risk of mortality in this cohort.

B cell phenotype and serum levels of interferons, BAFF, and APRIL in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19. RESULTS: We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the pre-IVIG presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients. CONCLUSIONS: Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.

The protective effect of COVID-19 vaccines on developing multisystem inflammatory syndrome in children (MIS-C): a systematic literature review and meta-analysis.

OBJECTIVE: To review whether the current COVID-19 vaccines can prevent the occurrence of multisystem inflammatory syndrome in children (MIS-C) and adolescents. METHODS: A systematic literature review and meta-analysis were performed. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Primary outcome was the efficacy of COVID-19 vaccination in preventing MIS-C development. The search was performed in PubMed and Embase. RESULTS: The review yielded 13 studies, which were included for critical appraisal and data extraction. The available studies showed a reduced incidence of MIS-C after mRNA COVID-19 vaccination in children aged 12-18 years. Four studies were eligible for meta-analysis and the pooled odds ratio for MIS-C in vaccinated children compared to unvaccinated children was 0.04 (95% confidence interval: 0.03-0.06). Additionally, the risk of MIS-C as an adverse effect of vaccination was much lower compared to the risk of MIS-C post-infection. CONCLUSIONS: Our systematic review highlights the current available evidence on the efficacy of COVID-19 vaccination in preventing MIS-C. The published studies so far - mainly conducted during the Delta wave - indicate that (original strain) COVID-19 mRNA vaccines in children are safe and associated with significantly less development of MIS-C. These findings further reinforce the recommendation for COVID-19 vaccination in children, which should be promoted and largely supported.

Assessing the Response of Biomarkers to Anti-Inflammatory Medications in PIMS-TS by Longitudinal Multilevel Modeling: Real-World Data from a UK Tertiary Center.

Background: Pediatric inflammatory multisystem syndrome temporarily associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PIMS-TS) is an acute complication of previous SARS-CoV-2 exposure. The relationship between inflammatory markers and anti-inflammatory medication in PIMS-TS is unknown. We retrospectively investigated the relationship between demographics, biomarkers, treatment, and length of stay (LOS) in this novel disease. Methods: We reviewed the case notes and blood tests of all patients who met the Royal College of Paediatrics and Child Health diagnostic criteria for PIMS-TS at a large tertiary center in the United Kingdom. Biomarker trajectories were modeled using log linear mixed effects, and factors affecting LOS in hospital were evaluated using multiple regression. Results: Between March 2020 and May 2022, a total of 56 patients attended Sheffield Children's Hospital with PIMS-TS, 70% male. Mean age was 7.4 ± 3.7 years and mean LOS 8.7 ± 4.5 days with 50% requiring intensive care and 20% requiring inotropes. Older males had shorter LOS than younger males (P = 0.04), not seen in females. Treatment included intravenous glucocorticoids in 93%, intravenous immunoglobulins (IVIG) in 77%, Anakinra in 11%, and infliximab in 1.8%. Biomarkers correlated poorly with trajectories that peaked at different times. C-reactive protein peaked first after median 1.3 days postadmission; while LFT's and neutrophils peaked after 3 days. Age had a large effect on some biomarkers, with older children having larger troponin and ferritin, and lower lymphocytes and platelets. Cumulative dose of glucocorticoids and IVIG had a statistically significant effect on some biomarkers, but effect size was small. Conclusions: The heterogenous nature of PIMS-TS highlights the importance of a multidisciplinary approach. Worse inflammatory markers in older children within our cohort may be an indication of a different disease process occurring at different ages. Future work to investigate the association between age and troponin and ferritin in hyperinflammatory states is warranted.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS) and Serous Effusions in a Child With Severe Hypoalbuminemia: A Case Report.

In April 2020, Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 or SARS­CoV­2 (PIMS-TS) was described for the first time in children. Since then, many countries have registered hundreds of cases with clinical similarities to Kawasaki disease. We report the case of a five-year-old boy diagnosed with PIMS-TS who presented myocarditis with serous effusions (pleurisy, ascites, pericarditis) due to severe hypoalbuminemia. This case sheds light on the importance of hypoalbuminemia in evaluating the severity of PIMS-TS and preventing its complications. The patient was successfully treated with intravenous immunoglobulins and oral prednisone.

Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland.

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.

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.

Role of Lung Ultrasonography (LUS) as a Tool for Evaluating Children with Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

BACKGROUND: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a novel entity. The inflammatory process involves the circulatory, digestive, respiratory, and central nervous systems, as well as the skin. Making a diagnosis requires extensive differential diagnoses, including lung imaging. The aim of our study was to retrospectively assess the pathologies found in lung ultrasound (LUS) in children diagnosed with PIMS-TS and to evaluate the usefulness of the examination in diagnostics and monitoring. METHODS: The study group consisted of 43 children diagnosed with PIMS-TS, in whom LUS was performed at least three times, including on admission to hospital, on discharge, and 3 months after disease onset. RESULTS: Pneumonia (mild to severe) was diagnosed in 91% of the patients based on the ultrasound image; the same number had at least one pathology, including consolidations, atelectasis, pleural effusion, and interstitial or interstitial-alveolar syndrome. By the time of discharge, the inflammatory changes had completely regressed in 19% of the children and partially in 81%. After 3 months, no pathologies were detected in the entire study group. CONCLUSION: LUS is a useful tool for diagnosing and monitoring children with PIMS-TS. Inflammatory lesions of the lungs resolve completely when the generalized inflammatory process subsides.