Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious condition associated with SARS-CoV-2 infection. The relationship between SARS-CoV-2 variants of concern (VOCs) and the occurrence and severity of MIS-C is unknown. We analyzed the dynamics of MIS-C in the Milan metropolitan area (Italy) during the COVID-19 pandemic, focusing on the epidemiologic trends and disease severity in relation to different VOCs in a single-center study. Fifty-seven MIS-C patients (mean 8.3 ± 3.8 years) admitted to the Pediatric Department of Buzzi Children's Hospital in Milan, Italy, between November 2020 and July 2022, were retrospectively included in the study. The SARS-CoV-2 variant was retrospectively identified from serological fingerprinting (profiles of serum antibodies targeting different variants of SARS-CoV-2 obtained by a label-free microarray biosensor) or by the variant of prevalence. Two main periods of MIS-C case accumulation were observed. The peak of MIS-C cases rate in December 2020 reached 0.6 cases per day, which is nearly double the rate observed in February 2022, despite the larger number of infected subjects. Although the WT variant exhibited a broader range of severity score values, the score distributions for the different variants do not show statistically relevant differences.

The results clearly show a decrease in the incidence of MIS-C in relation to infections, but also support the concept that severity of MIS-C remained essentially unchanged across different virus variants, including Omicron. The course of MIS-C, once initiated, is independent from the characteristics of the triggering variants, although later variants may be considered less likely to induce MIS-C.

• MIS-C is a rare systemic inflammatory disorder that arises as a post-infectious complication temporally related to SARS-CoV-2 infection. • Fluctuations in MIS-C incidence were observed throughout the pandemic, with the latest variants associated with a lower incidence.

• The SARS-CoV-2 variant of infection can be retrospectively confirmed by serum antibody fingerprinting using a label-free microarray biosensor. • Despite the decreasing incidence, MIS-C severity has remained essentially unchanged across SARS-CoV-2 variants.

To characterize the clinical phenotypes of SARS-CoV-2 infection in hospitalized children as part of the EPICO multicenter cohort study.

We included hospitalized children with confirmed SARS-CoV-2 infection from Colombian and Spanish institutions to assess disease evolution and outcomes. Cluster analysis was performed to identify clinical phenotypes.

A total of 2318 patients were included (55% male, 36% infants). Five phenotype clusters emerged: Cluster 1 (26.5%): infants without comorbidities, low PICU admissions and mortality; Cluster 2 (18.5%): respiratory comorbidities, high microorganism co-detection and mortality; Cluster 3 (11.5%): fever, gastrointestinal symptoms, high PICU admissions; Cluster 4 (32%): mild unspecific symptoms, low mortality; Cluster 5 (11.3%): adolescents without comorbidities, low co-detection and hospitalization rates. Findings were consistent across both countries.

Identifying clinical phenotypes of SARS-CoV-2 in children may improve risk stratification and guide future management strategies.

Multisystem Inflammatory Syndrome in Children: A Comprehensive Review over the Past Five Years This review explores many facets of Multisystem Inflammatory Syndrome in Children (MIS-C) over the previous 5 years. In the time since the COVID 19 pandemic gripped our medical systems, we can now explore the data that has been collected from the previous years. The literature has allowed us to better understand the impact of COVID 19 and the post illness occurrence of a severe systemic inflammatory disease on our youngest patient populations. This paper will outline the pathophysiology of MIS-C, the treatments utilized, short and long-term patient outcomes including epidemiological factors.

To summarize the latest research on the epidemiology, pathogenesis, diagnosis, and treatment of multisystem inflammatory syndrome in children (MIS-C).

The epidemiology of MIS-C has been dynamic since its initial description. The pathogenesis remains poorly understood. Case definitions of MIS-C have evolved over time, and practice patterns for treating MIS-C are variable with generally positive long-term outcomes yet persistent changes noted. MIS-C has become less prevalent and less severe over time, yet racial and ethnic disparities persist, and vaccination against COVID-19 is highly effective in preventing this disease. The link between acute infection and subsequent inflammation is not well understood, with growing evidence describing its immunologic signature. Newer case definitions require excluding other inflammatory conditions, including Kawasaki Disease (KD), before diagnosing MIS-C. Corticosteroid monotherapy may be non-inferior to IVIg alone or combination IVIg plus corticosteroids for initial treatment, distinguishing the approaches to MIS-C and KD. A wide range of biologic therapies have been employed for rescue therapy with general success and no clear benefit of one over another. Despite reports of a high rate of coronary artery abnormality regression and resolution of heart failure, long-term studies suggest persistent changes to cardiac function. The long-term effects of MIS-C continue to be active areas of research.

To explore the trends and changes in the transport of children to paediatric intensive care units (PICUs) between 2013 and 2022.

Retrospective analysis of routinely collected data.

Children transported for care in a PICU in the UK and Ireland aged<16 years.

None.

There were 43 058 transports to a PICU involving 36 438 children from 2013 to 2022 with the majority of children requiring only one transport. The number of transports increased from 4131 (2013) to 4792 (2022). Over the study period the percentage of children aged under 1 year who were transported decreased from 50.2% to 45.2% and similarly, the percentage who were invasively ventilated also decreased from 81.1% to 70.2%. Conversely, the use of non-invasive ventilation during transports increased slightly from 4.0% to 7.0%. The percentage of transports where a parent was able to accompany the child increased over time (2013: 66.2% to 2019: 74.9%), although there were reductions due to the COVID-19 pandemic and requirements for social distancing (2020: 52.4%).

We have demonstrated an increased use of specialist paediatric transport services and changes in the PICU population over time. Routine data collection from the transport services provide a means to measure improvements and changes over time in the service provided to critically ill children and young people who need transport to the PICU.

Group A Streptococci (GAS) may cause infections of the pharynx and soft tissues and invasive infections in children (iGAS). A significant increase in severe iGAS infections has been reported in Europe since the fall of 2022.

This retrospective study aims to analyse clinical data of children with invasive and non-invasive GAS infections in the post-COVID-19 pandemic era, searching for predisposing factors to developing invasive infections.

History and clinical data of patients hospitalised due to or with coexisting GAS infections were analysed. iGAS and non-iGAS infections were compared.

The cohort comprised 45 children (median age 7 years). 31(69 %) children developed iGAS infections - sepsis with toxic shock syndrome (TSS) (4 children-13 %), deep soft tissue infections (3-10 %), meningitis (2-6 %), pneumonia (2-6 %) or respiratory tract infections - sinusitis or otitis (4-12 %). iGAS children developed complications more frequently (100 % vs 21 %, p < 0.0001) and required prolonged treatment (median 15 vs 10 days, p = 0.0001). Preceding or coexisting viral infections were more common in iGAS children (87 % vs 14 %; p < 0.0001). CRP and PCT were significantly higher in the iGAS group (median 17.95 vs 3.97 mg/dl, p = 0.0002; 6.8 vs 0.05 ng/ml, p = 0.0001, respectively). The multiple logistic regression revealed that preceding or coexisting viral infections and the rise in CRP level increased the risk of iGAS infections. The CRP cut-off > 14.94 mg/dl showed 68.2 % sensitivity (CI 45.13-86.14 %) and 100 % specificity (69.15-100 %).

Our study shows increased incidence and severity of GAS infections among hospitalised children. Previous or coexisting viral infections and CRP with cut-off > 14.94 mg/dl were significant risk factors.

Introduction. This study aims to describe the clinical and paraclinical characteristics of Multisysteminflammatory syndrome in children (MIS-C). Methods. A retrospective study encompassing 52 children diagnosed with MIS-C according to the World Health Organization criteria, over a 3-year period at Abderrahim Harrouchi Hospital in Morocco. Results. The median age was 6 years (IQR: 1-14), with a sex ratio of 1.16 (28 boys and 24 girls). Clinical manifestations were predominantly characterized by fever in all cases (100%), respiratory and gastrointestinal symptoms in 30 cases (58%) and 23 cases (44%) respectively, and shock in 9 cases (17%). We noted a myocarditis in 6 cases (12%). The treatment comprised intravenous human Immunoglobulin combined with methylprednisolone in all patients (100%). Conclusion. The characteristics of our MIS-C patients were similar to those in the literature, but more studies are needed to confirm these results.

The COVID-19 pandemic has brought attention to a newly identified syndrome of multisystem inflammation. This potentially fatal complication of the disease was initially observed in children and later in adults. It affects primarily unvaccinated patients and may manifest within a timeframe of 2-12 weeks following infection. Soluble urokinase plasminogen activator receptor (suPAR), a novel biomarker, highlights the severity of inflammation and the degree of immune system activation. Herein, we report a case of a patient with multisystem inflammatory syndrome in adults (MIS-A) and markedly elevated suPAR levels, successfully treated with interleukin-1 (IL-1) receptor antagonist. A 59-year-old female was admitted to our hospital due to febrile illness (up to 40°C) with chills, vomiting, non-bloody diarrhea, and abdominal pain for four days prior to her admission. She tested positive for SARS-CoV-2 12 weeks before her presentation. During hospitalization, the patient deteriorated clinically with multiorgan involvement and hemodynamically instability, with concomitant markedly elevated inflammatory markers. Extensive workup with high suPAR levels led to post-COVID-19 MIS-A diagnosis, and treatment with dexamethasone and an interleukin-1 receptor antagonist (IL-1ra), anakinra, was administered. The subcutaneous injection of anakinra effectively and safely deterred MIS-A. Further research is needed to investigate the role of interleukin-1 inhibitors for the management of this potentially life-threatening condition.

To accommodate the unprecedented demand for critical care beds during the first surge of the coronavirus disease 2019 (COVID-19) pandemic in the United Kingdom, hospitals had to adapt, restructure, and collaborate to provide the best possible care for the pediatric and adult populations. This single-center experience outlines the considerations our hospital took into account when planning for this restructure and the steps taken to ensure a successful execution of the task. Cross-specialty collaboration between the pediatric and adult critical care teams adopted a unique approach to care for only critically ill COVID-19 positive adult patients in the pediatric intensive care unit (PICU), transferring out critically unwell children at an early stage before the adult intensive care unit (AICU) became overwhelmed (nonhybrid model). This was designed to be in a staggered fashion, before allowing the AICU to overflow. This approach enabled the adult critical care team to support pediatric colleagues in learning the nuances of looking after critically ill adults prior to the service being saturated by the predicted supersurge. The success of the operation hinged on two things. First, PICU staff continuing to work in a familiar environment with their usual clinical team and second, the gradual and controlled admission of adult patients into PICU before the peak in demand for critical care beds. This design helped protect staff morale and build confidence in their new clinical role. The overall case fatality of invasively ventilated patients with COVID-19 in our hospital during the first surge was 32%, which is lower than the global average of 45%. This serves as evidence that this nonhybrid model is safe and sustainable.

Pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; PIMS-TS) is a novel condition with persistent fever, inflammation, and single or multiorgan dysfunction. We aimed to describe the characteristics of children more severely affected and our clinical approach. We retrospectively collected clinical, treatment, and early outcomes data during a 3-month period in a pediatric intensive care unit (PICU) of a tertiary university hospital in Portugal. Twelve children who fulfilled the Royal College of Pediatrics and Child Health case definition were hospitalized, seven needed PICU admission. Median age was 13 years and three were overweight, with no other comorbidity. All had positive immunoglobulin G antibodies for SARS-CoV-2. All presented with prolonged fever, asthenia, hypotension, and shock. Other prominent symptoms were abdominal complaints and rash. All patients had leukocytosis, neutrophilia, and marked elevation of inflammatory markers. Cardiac involvement was observed in all patients with elevated levels of troponin and B-type natriuretic peptide along with left ventricular hypokinesis. Depressed left ventricular function was observed in four patients. All patients received broad-spectrum antibiotics, intravenous immunoglobulin, methylprednisolone, low-dose aspirin, and vasoactive medications. Four patients received prophylactic enoxaparin. All patients needed supplementary oxygen; however, high-flow oxygen therapy and noninvasive ventilatory support with positive end-expiratory pressure were required in three and two patients, respectively. Five patients required invasive mechanical ventilation. The mean duration of PICU stay was 7.1 days. The median Pediatric Risk of Mortality-III score was 9 and no mortality was observed. PIMS-TS demands a prompt and multidisciplinary approach. Risk factors, best clinical pathway, and long-term complications are still unknown.

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, persons ≥65 years of age and healthcare personnel represented the most vulnerable groups with respect to risk of infection, severe illness, and death. However, as the pandemic progressed, there was an increasingly detrimental effect on young children and adolescents. Severe disease and hospitalization increased over time in pediatric populations, and containment measures created substantial psychosocial, educational, and economic challenges for young people. Vaccination of children against COVID-19 has been shown to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and severe outcomes in pediatric populations and may also help to prevent the spread of variants of concern and improve community immunity. This review discusses the burden of COVID-19 on children throughout the pandemic, the role of children in disease transmission, and the impact of COVID-19 vaccination.

We conducted an Umbrella review of eligible studies to evaluate what patient features have been investigated in the multisystem inflammatory syndrome in children (MIS-C) population, in order to guide future investigations. We comprehensively searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from December 1, 2019 to the May 6, 2022. The time period was limited to cover the coronavirus disease-2019 (COVID-19) pandemic period. The protocol was registered in the PROSPERO registry (CRD42022340228). Eligible studies included (1) a study population of pediatric patients ≤21 years of age diagnosed with MIS-C; (2) an original Systematic review or Mata-analysis; (3) published 2020 afterward; and (4) was published in English. A total of 41 studies met inclusion criteria and underwent qualitative analysis. 28 studies reported outcome data of MIS-C. 22 studies selected clinical features of MIS-C, and 6 studies chose demographic data as a main topic. The mortality rate for children with MIS-C was 1.9% (interquartile range (IQR) 0.48), the ICU admission rate was 72.6% (IQR 8.3), and the extracorporeal membrane oxygenation rate was 4.7% (IQR 2.0). A meta-analysis of eligible studies found that cerebral natriuretic peptide in children with MIS-C was higher than that in children with COVID-19, and that the use of intravenous immunoglobulin (IVIG) in combination with glucocorticoids to treat MIS-C compared to IVIG alone was associated with lower treatment failure. In the future, for patients with MIS-C, studies focused on safety of surgery requiring general anesthesia, risk factors, treatment, and long-term outcomes are warranted.

Coronavirus is an important pathogen causing disease in humans and animals. At the end of 2019, an investigation into an increase in pneumonia cases in Wuhan, Hubei Province, China, found that the cause was a new coronavirus. This disease, which spread rapidly across China and caused an outbreak worldwide, resulted in a pandemic. Although this virus has previously been referred to as 2019-nCoV, which causes coronavirus disease 2019 (COVID-19), later it was named severe acute respiratory syndrome coronavirus 2. Children were usually asymptomatic and rarely severely affected. In April 2020, reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock syndrome. This clinical picture was later defined as multisystem inflammatory syndrome in children. Since then, similarly affected children as well as cases with other cardiac complications have been reported in other parts of the world. In this review, we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

Osteopetrosis is a group of geneticall heterogeneous disorders resulting from impaired osteoclast function and bone resorption. The identification of specific genetic mutations can yield important prognostic and therapeutic implications. Herein, we present the diagnosis and successful application of hematopoietic stem cell transplantation (HSCT) in a patient with osteopetrosis caused by carbonic anhydrase II deficiency (Intermediate osteopetrosis).

Herein, we describe a 2.5-year-old male patient born to consanguineous parents who presented at 8-month-old with hydrocephaly, brain shunt, and developmental delay. Later at 9 months old, he was found to have eye disorder such as nystagmus, fracture of the elbow, abnormal skeletal survey, normal cell blood count (CBC), and severe hypocellularity in the bone marrow. Further evaluation showed renal tubular acidosis type 2. Whole-exome sequencing revealed a pathogenic homozygous variant in intron 2 of the carbonic anhydrase 2 gene (CA2) gene (c.232 + 1 G>T). The diagnosis of intermediate autosomal recessive osteopetrosis was established, and allogenic HSCT from his mother, a full-matched related donor (MRD), was planned. The conditioning regimen included Busulfan, Fludarabine, and Rabbit anti-thymocyte globulin. Cyclosporine and Mycophenolate Mofetil were used for graft-versus-host-disease prophylaxis. He Engrafted on day +13, and 95% chimerism was achieved. He is currently doing well without immunosuppressive therapy, now 12 months post HSCT, with normal calcium level and improving visual quality and FISH analysis revealed complete donor chimerism.

HSCT could be a promising curative treatment for intermediate osteopetrosis and can provide long-term survival. Ongoing challenges in various aspects of HSCT remain to be addressed.

The impact of long-term Coronavirus disease 2019 (COVID-19) on the pediatric population is still not well understood. This study was designed to estimate the magnitude of COVID-19 long-term morbidity 3-6 months after the date of diagnosis.

A retrospective study of all Clalit Health Services members in Israel aged 1-16 years who tested positive for SARS-CoV-2 between April 1, 2020 and March 31, 2021. Controls, who had no previous diagnosis of COVID-19, were one-to-one matched to 65,548 COVID-19-positive children and teens, and were assigned the infection dates of their matches as their index date. Matching included age, sex, socio-economic score, and societal sector. Individuals were excluded from the study if they had severe medical conditions before the diagnosis such as cancer, diabetes, chronic respiratory diseases, and/or abnormal physiological development. Generalized Estimating Equations were used to estimate the associations between COVID-19 and the use of medical services. The analysis focused on the 3-6 months after the infection date. Adjustments were made for demographics and for the use of medical services 6-12 and 3-6 months before the infection date. The latter was necessary because of observed disparities in medical service utilization between the groups before the COVID-19 diagnosis, despite the matching process.

Statistically significant differences were only found for referrals for mental health services [adjusted relative-risk (RR) 1·51, 95%CI 1·15 - 1·96; adjusted risk-difference (RD) 0·001, 95%CI 0·0006 - 0·002], and medication prescriptions of any kind (RR 1·03, 95%CI 1·01-1·06; RD 0·01 95%CI 0·004 - 0·02).

The significant increase in medication prescriptions and mental health service referrals support the hypothesis that COVID-19 is associated with long-lasting morbidities in children and adolescents aged 1-16 years. However, the risk difference in both instances was small, suggesting a minor impact on medical services.

Early recognition and treatment of Multisystem Inflammatory Syndrome in Children (MIS-C) within the context of COVID-19 infection is crucial for improved outcomes. Prompt intervention with IVIG and steroids leads to significant improvement in a severe case of MIS-C. Clinicians should be vigilant for MIS-C symptoms and initiate timely management.

We report a case involving a fourteen-year-old male with COVID-19 infection who developed multisystem inflammatory disease. A previously healthy child presented with a history of 10 days of fever and cough, along with diarrhea, and vomiting for 3 days. His COVID-19 infection was confirmed through Polymerase Chain Reaction (PCR), and the laboratory values were remarkable for high levels of C-reactive protein, D-dimers, B-type natriuretic peptide (BNP), and troponin I. He developed circulatory shock on the second day of the presentation and needed inotropic support. Steroids and intravenous immunoglobulin (IVIG) were started in light of Multisystem Inflammatory Syndrome in Children (MIS-C), which improved his condition. Thus, during the management of COVID-19 infection, early detection and a careful clinical characterization for MIS-C are essential.

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).

Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17%-75%) and heart failure (52%-53%). Intravenous immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that an interleukin-1 (IL-1) receptor antagonist, namely anakinra, may be a valuable add-on to the 2019 novel coronavirus disease (COVID-19) treatment for refractory patients. The purpose of this study was to describe the clinico-biological characteristics of patients treated with anakinra as well as the efficacy and safety of subcutaneous anakinra therapy in this condition.

The prospective multicentre study of children hospitalized for MIS-C between March 2020 and September 2022, including 23 international paediatric centres, followed for a mean duration of 3.072 ± 3.508 months. The patient data were extracted from the Juvenile Inflammatory Rheumatism (JIR) cohort. The clinico-pathological characteristics, cardiac ultrasound data, and adverse events were reported in patients receiving anakinra.

Of the 470 children admitted with MIS-C, 18 French patients (50% girls) with a mean age of 10.06 ± 3.9 years were treated with subcutaneous anakinra. Anakinra was used in two situations, macrophage activation syndrome (MAS) (4 patients) and heart failure (14 patients) with a median left ventricular ejection fraction (LVEF) of 39.5% (30%-45%). The average dose of anakinra received was 2.53 ± 1.3 mg/kg/day for a median duration of 3 days. Prior to introduction, 78% (n = 14/18) of the patients had received CST and 56% (n = 10/18) had received IVIG. Only two patients received IVIG alone and six received CST alone plus anakinra. In 10% of cases, IVIG was poorly tolerated from a cardiovascular point of view and was discontinued. Transient elevations in serum transaminases were noted in four patients on anakinra without the need for treatment or dose modification. In all patients, rapid (48 h) improvement in myocardial function was observed (LVEF > 55%) with a concomitant significant decrease in myocardial enzymes (p < 0.05). All patients survived with complete recovery of cardiac function without sequelae.

Subcutaneous anakinra appears to be a safe and effective treatment for the management of heart failure or MAS in MIS-C patients. The value of IVIG in these two situations remains to be reviewed.

Several studies have reported a higher frequency and greater morbidity and mortality of multisystem inflammatory syndrome in children (MIS-C) of black African descent.

We aimed to describe the clinical, laboratory and echocardiographic characteristics as well as outcomes of children with MIS-C requiring admission to a pediatric intensive care unit (PICU) in the French West Indies (FWI), where the majority of the population is Afro-Caribbean.

Ambidirectional observational cohort study between April 1, 2020 and August 31, 2022. Children (age ≤18 years) with MIS-C and organ failure were included. Every patient was monitored and treated following the same protocol, with repeated biological tests, echocardiography, intravenous steroids and polyvalent immunoglobulins. The primary outcomes were clinical, laboratory and echocardiography characteristics.

Forty children (median age 7 years, range: 5-11) were included. The majority (77 %) were included prospectively. Thirty-five (87 %) had gastrointestinal symptoms, 30 (75 %) presented initial heart failure (with persisting diastolic dysfunction at day 7) and 18 (45 %) had pericarditis. Sixteen (40 %) were in cardiogenic shock and required inotropic support. Median duration of inotropic support and hospitalization in PICU were respectively 4 and 5 days. The evolution curves of the inflammatory variables matched after treatment. The clinical outcomes were favorable. The Delta variant was associated with the highest incidence of MIS-C.

This is the first description of MIS-C course among children of Afro-Caribbean descent. The outcomes were good, without any death or cardiac sequelae. Our work does not support an ethnic susceptibility for severity of MIS-C in Afro-Caribbean population.

This study aimed to assess different clinical, disease severity, laboratory, treatment, and outcome-related factors of COVID-19 positive infants admitted to a pediatric intensive care unit (PICU) and to compare these parameters with COVID-19 positive noninfants (1-12 years of age) who also required intensive care admission. This retrospective observational study was conducted in a PICU of a tertiary care, dedicated pediatric COVID facility. The clinical, epidemiological, laboratory parameters, and treatment outcomes of COVID-19 infected infants admitted to the PICU were recorded and analyzed. During comparison with the noninfant group, malignancy and coinfection with dengue and scrub typhus were excluded from both groups. A total 313 COVID-19 positive children aged from 1 month to 12 years old were admitted, of which 115 (36.7%) children required PICU admission. Infants constituted 37.4% of total PICU admissions. Most common symptoms were respiratory (83.7%) followed by fever (60.5%). Fifteen (34.9%) infants presented with shock. Ten infants (23.3%) had myocardial dysfunction. C-reactive protein (CRP) and ferritin were high in 60.5 and 16.7% infants, respectively. Fourteen infants needed invasive mechanical ventilation. Nine patients had acute respiratory distress syndrome (ARDS) and five had MIS-C. However, 53.5% infants had different comorbidities. Four infants died and all of them had severe comorbidities. Respiratory distress ( p  = 0.009), pediatric sequential organ failure assessment score ( p  = 0.032) and number of ARDS cases ( p  = 0.044) were significantly higher in infants than noninfants. Infants are one of the most vulnerable groups of children suffering from serious illness from COVID-19 infection requiring PICU admission due to predominantly respiratory involvement. Overall outcome was good among infants without significant comorbidity.

Due to its link with the 2019 coronavirus, the multisystem inflammatory syndrome in children (MISC) has garnered considerable international interest. The aim of this study, in which MISC patients were evaluated multicenter, and the data of the third period of the Turk-MISC study group, to compare the clinical and laboratory characteristics and outcomes of MISC patients who did and did not require admission to an intensive care unit (ICU).

This retrospective multicenter observational study was carried out between June 11, 2021, and January 01, 2022. The demographics, complaints, laboratory results, system involvements, and outcomes of the patients were documented.

A total of 601 patients were enrolled; 157 patients (26.1%) required hospitalization in the intensive care unit (ICU). Median age was 8 years (interquartile range (IQR) 4.5-11.3 years. The proportion of Kawasaki disease-like features in the ICU group was significantly higher than in the non-ICU group (56.1% vs. 43.2% p = 0.006). The ICU group had considerably lower counts of both lymphocytes and platelets (lymphocyte count 900 vs. 1280 cells × μL, platelet count 153 vs. 212 cells × 103/ μL, all for p< 0.001). C-reactive protein, procalcitonin, and ferritin levels were significantly higher in the ICU group (CRP 164 vs. 129 mg/L, procalcitonin 9.2 vs. 2.2 μg/L, ferritin 644 vs. 334 μg/L, all for p< 0.001). Being between ages 5-12 and older than 12 increased the likelihood of hospitalization in the ICU by four [95% confidence intervals (CI)1.971-8.627] and six times (95% CI 2.575-14.654), respectively, compared to being between the ages 0-5. A one-unit increase in log D-dimer (µg/L) and log troponin (ng/L) was also demonstrated to increase the need for intensive care by 1.8 (95% CI 1.079-3.233) and 1.4 times (95% CI 1.133-1.789), respectively.     Conclusion: By comparing this study to our other studies, we found that the median age of MISC patients has been rising. Patients requiring an ICU stay had considerably higher levels of procalcitonin, CRP, and ferritin but significantly lower levels of lymphocyte and thrombocyte. In particular, high levels of procalcitonin in the serum might serve as a valuable laboratory marker for anticipating the need for intensive care.

• Lymphopenia and thrombocytopenia were an independent predictor factors in patients with MISC who needed to stay in intensive care unit. • The possibility of the need to stay in the intensive care unit in patients with MISC who had Kawasaki disease-like findings was controversial compared with those who did not.

• A one-unit increase log D dimer and log troponin was demonstrated to require for intensive care unit by 1.8 and 1.4 times, respectively. • Serum procalcitonin levels had the best performance to predict stay in the intensive care unit stay.

Multisystem inflammatory syndrome in children is a rare and potentially life-threatening disease that is associated with SARS-CoV-2 infection, characterized by hyperinflammation and multiorgan involvement. Cardiovascular involvement is common, including myocardial dysfunction often leading to cardiogenic shock. We present the case of a 17-year-old boy with fever, odynophagia, maculopapular rash and abdominal pain who developed a cardiogenic shock. Due to progressive deterioration of cardiac function despite optimized vasoactive support, veno-arterial extracorporeal membrane oxygenation support was initiated 12 hours after admission, with successful decannulation after seven days and discharge after 23 days, with normal cardiac function. The patient received corticosteroids and intravenous immunoglobulin. Early recognition and intensive care support are crucial for ensuring a successful outcome in severe cases of multisystem inflammatory syndrome. In cases of severe cardiogenic shock, extracorporeal membrane oxygenation support can be critical for survival and rapid recovery.

This systematic review and meta-analysis were conducted to evaluate the prevalence of cardiac manifestations associated with multisystem inflammatory syndrome in children worldwide. We conducted electronic searches in Ovid MEDLINE, Ovid EMBASE, and the World Health Organization COVID-19 Literature Database from the inception of the SARS-CoV-2 pandemic to 1 January, 2022. Three authors independently screened the abstracts to determine eligibility, assessed methodology in the full texts, and extracted the data.We identified 2848 citations; 94 studies (14,932 patients) were included. The prevalence of vasopressors was 48.2% (95% CI 45.1%, 51.3%), left ventricular systolic dysfunction occurred in 37.2% (95% CI 34.1%, 40.3%), myocarditis in 34.1% (95% CI 30.5%, 37.8%), electrocardiographic dysrhythmias and abnormalities detected in 23.1% (95% CI 18.8%, 27.6%), coronary abnormalities identified in 18% (95% CI 16%, 20%), extracorporeal membrane oxygenation deployed in 2.2% (95% CI 1.7%, 2.8%), and mortality rate of 2.2% (95% CI 1.7%, 2.7%). A sensitivity analysis was performed after removing eleven studies with high bias, and the adjusted prevalence was not different than the original evaluation.In this meta-analysis of the largest cohort of multisystem inflammatory syndrome in children patients to date, we established the most accurate prevalence of the most common cardiac manifestations. Providers will subsequently have more precise data to anticipate patient outcomes and approach discussions concerning the frequency of monitoring outside the acute hospital period.

Multisystem inflammatory syndrome in children (MISC) is a phenomenon that appeared in children infected with or exposed to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The typical onset of MISC is 4-6 weeks following SARS-CoV-2 infection and is formulated to be due to an immune response.

Our study retrospectively analyzed data from a tertiary center in United Arab Emirates of MISC patients who were admitted to either general pediatric wards or pediatric intensive care (PICU) or who came exclusively for follow-up (post-PICU admission) from May 2020 to August 2021.

The total sample size was 50 patients, and the study included a comparison of MISC-PICU admissions with MISC-non-PICU admissions. The MISC-PICU sample size was 18 patients, 50% females, with mean age of 8.3 years all were previously healthy. MISC-PICU patients had deranged blood counts with a lower hemoglobin count, a more pronounced lymphopenia and thrombocytopenia along with hypoalbuminemia. MISC-PICU patients presented with relatively higher inflammatory markers: C-reactive protein, procalcitonin, ferritin, and d-dimer. Immunological studies were significantly higher for interleukin-6 levels in PICU patients. On echocardiography, higher myocardial dysfunction was more notable in MISC-PICU patients. Likewise, MISC-PICU patients were provided with more extensive therapy. As part of our study course, we reevaluated our MISC-PICU patients twice, once at 48 h post-PICU admission and again 4-6 weeks after discharge from the hospital. No deaths have been recorded in the cohort.

This study evaluated risk factors of MISC and potential severity features. Follow-up of patients on discharge showed improvement across all domains.

The purpose of this study is to describe the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) disease characteristics and management in children admitted to the pediatric intensive care units (PICU).

The present study was based on a national multicentric prospective registry including PICU patients with SARS-CoV2 infection or symptoms of multisystem inflammatory syndrome in children (MIS-C).

A total of 298 patients were admitted to 41 different Spanish PICUs. A total of 76% of them were previously healthy. The most frequent manifestation was MIS-C (69.8%). On admission, 59.4% of patients did not have respiratory distress, and only 17.4% needed conventional mechanical ventilation (MV). The need for MV was associated with age (incidence rate ratios [IRR] 1.21, p < .012), pediatric sequential organ failure assessment score (p-SOFA) Score (IRR 1.12, p = .001), and need for transfusion (IRR 4.5, p < .004) in MIS-C patients, and with vasoactive drug use (IRR 2.73, p = .022) and the diagnosis of acute respiratory distress syndrome (IRR 2.83, p = .018) in patients admitted for other reasons. During the first day of admission, 56% of patients met shock criteria and 50.7% needed vasoactive drugs. In MIS-C patients, their use was associated with higher p-SOFA score (IRR 1.06, p < .001) and with the diagnosis of shock (IRR 5.78, p < .001). In patients without MIS-C, it was associated with higher p-SOFA score (IRR 1.05, p = .022). The mortality rate was 3%, being lower in MIS-C patients compared to patients admitted for other reasons (0.5% vs. 9.4%, p < .001). It was also lower in previously healthy patients compared to patients with previous comorbidities (0.9% vs. 9.7%, p < .001).

Severe SARS-CoV2 infection is uncommon in the pediatric population. In our series, respiratory distress was rare, being MIS-C the most frequent cause of PICU admission related to SARS-CoV2. In most cases, the course of the disease was mild except in children with previous diseases.

Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear.

To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children.

Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded.

SARS-CoV-2 hospitalization during the stipulated time frame.

The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy.

Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children.

This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Multisystem inflammatory syndrome in children secondary to coronavirus disease 2019 (COVID-19) (MIS-C) is very common and may present with clinical features similar to Kawasaki disease but is rarely reported in neonates (MIS-N). Any history of maternal upper respiratory tract infection should raise suspicion of MIS-N secondary to COVID-19 in critically ill neonates.

The authors present a term neonate with gradually progressive respiratory distress requiring mechanical ventilation with marked improvement after starting immunoglobulin and steroids after blood investigations revealed high IgG COVID-19 antibody titers.

Admitted to the Neonatal Intensive Care Unit as he received bag and mask ventilation for 30 s following delivery, he was kept under oxygen via nasal prongs; but he still had nasal flaring, subcostal retraction, and tachypnea. All the blood investigations were within normal limits except for elevated C-reactive protein.

With no improvement despite oxygen via nasal prongs, he was kept under bubble continuous positive airway pressure with positive end-expiratory pressure of 5 cm of H2O. With no improvement even after 24 h of noninvasive ventilation, he was kept under mechanical ventilation in assisted pressure-controlled mode with a peak inspiratory pressure of 22 cm H2O and respiratory rate of 40 breaths/minute. As the mother gave a history of on-and-off cough for almost a month, samples were sent for COVID-19 antibodies which came out to be positive with very high titers of IgG antibodies. Intravenous steroids, immunoglobulin, and subcutaneous low molecular weight heparin were started and marked improvement was noted. The peak inspiratory pressure and FiO2 were gradually tapered off, and he was extubated on the 10th day of mechanical ventilation.

Multisystem inflammatory syndrome in neonates is rare but should always be considered in neonates with multisystem involvement and a history of maternal upper respiratory tract infection after excluding all other causes.

Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders.

Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls.

ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C.

Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation.

The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

Multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a life-threatening condition that often requires intensive care unit (ICU) admission. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. The study included 166 patients (99 boys, 67 girls) aged 4 months-17 years (median 8.2 years). The criterion of severity was the fact of ICU admission. To conduct a comparative analysis, MIS-C patients were divided into two groups: patients hospitalized in the ICU (n = 84, 50.6%) and those who did not need ICU admission (n = 82, 49.4%). Patients with a more severe course of MIS-C were significantly older. They had a higher frequency of signs such as rash, swelling, hepatomegaly, splenomegaly, and neurological and respiratory symptoms. Hypotension/shock and myocardial involvement were much more common in patients with severe MIS-C. These patients had a more significant increase in CRP, creatinine, troponin, and D-dimer levels. Additionally, the presence of macrophage activation syndrome was higher in patients admitted to the ICU. Conclusion: Nineteen predictors of severe course of MIS-C were found, out of which hepatomegaly, splenomegaly, D-dimer > 2568 ng/mL, troponin > 10 pg/mL were mainly associated with the probability of being classified as early predictors of severe MIS-C requiring ICU admission.