Multisystem inflammatory syndrome of childhood (MIS-C) is a newly recognized entity associated with COVID-19 in children. The objective was to describe the clinical course for 74 patients diagnosed with this disease.

A multicenter retrospective study including 5 major hospitals in Jordan was conducted. Data from children admitted with confirmed SARS-CoV-2 infection or were in close contact with confirmed cases were collected. Total of 74 patients were diagnosed with MIS-C. Clinical, laboratory, radiological and therapeutic data were collected by retrospective chart review.

Fever, abdominal pain, hypoxia and other manifestation occurred. Cardiac findings were less common and did not include coronary findings. Treatments were mainly Corticosteroids and IVIG. No mortality was found in this series but serious disease occurred and some patients were admitted to Pediatric Intensive Care Unit.

This study described the epidemiology, clinical course, management, and outcome of MIS-C cases in Jordan. The findings were consistent with what has been described from other regions globally. There was a wide spectrum in the severity of presentation. Abdominal pain was more prevalent and some children were misdiagnosed as surgical acute abdomen.

The COVID-19 pandemic brought several diagnostic challenges, including the post-infectious sequelae multisystem inflammatory syndrome in children (MIS-C). Some of the clinical features of this syndrome can be found in other pathologies such as Kawasaki disease, toxic shock syndrome, and endemic typhus. Endemic typhus, or murine typhus, is an acute infection treated much differently than MIS-C, so early detection is crucial to a favorable prognosis for patients with these disorders. Clinical Decision Support Systems (CDSS) are computer systems designed to support the decision-making of medical teams about their patients and intended to improve uprising clinical challenges in healthcare. In this article, we present a CDSS to distinguish between MIS-C and typhus, which includes a scoring system that allows the timely distinction of both pathologies using only clinical and laboratory features typically available within the first six hours of presentation to the Emergency Department. The proposed approach was trained and tested on datasets of 87 typhus patients and 133 MIS-C patients. A comparison was made against five well-known statistical and machine-learning models. A second dataset with 111 MIS-C patients was used to verify the effectiveness and robustness of the AI-MET system. The performance assessment for AI-MET and the five statistical and machine learning models was performed by computing sensitivity, specificity, accuracy, and precision. The AI-MET system scores 100 percent in the five metrics used on the training and testing dataset and 99 percent on the validation dataset. Statistical analysis tests were also performed to evaluate the robustness and ensure a thorough and balanced evaluation, in addition to demonstrating the statistical significance of MET-30 performance compared to the baseline models.

Cardiac injury is the critical issue in children with MIS-C, particularly coronary artery dilation. This study aimed to describe the prevalence, risk factors associated with coronary artery abnormalities, and their progression after 3 months of follow-up in MIS-C children in Vietnam. A prospective multicenter case series study was conducted on MIS-C patients diagnosed per WHO criteria from September 2021 to February 2023 at the two largest pediatric hospitals in southern Vietnam. Data on demographics, clinical features, laboratory findings, and treatments during the acute phase of MIS-C were collected. Patients were followed for 3 months post-discharge and categorized into normal and abnormal coronary artery groups for comparative analysis. Among 195 patients (mean age 6.3 years; male to female ratio 1.5:1), 33.3% exhibited coronary artery abnormalities at admission. Treatment included a combination of intravenous immunoglobulin (IVIG) and corticosteroids (53.3%), corticosteroids alone (42.6%), and IVIG alone (4.1%). After 3 months, only 3.6% of patients had persistent coronary artery abnormalities. Independent risk factors for coronary artery dilation included male sex (OR 4.59; 95% CI 1.62-12.94; p = 0.004), Kawasaki-like phenotype (OR 6.42; 95% CI 2.25-18.33; p = 0.001), and mesenteric lymphadenitis (OR 8.79; 95% CI 1.74-44.31; p = 0.008).

Coronary artery dilation in MIS-C patients shows a favorable recovery trajectory after a 3-month follow-up. Male sex, Kawasaki-like MIS-C, and mesenteric lymphadenitis are independent risk factors for coronary artery dilation in MIS-C patients.

• Multisystem inflammatory syndrome in children (MIS-C) is a severe inflammatory syndrome following SARS-CoV-2 infection, often leading to cardiac complications, particularly coronary artery dilation.

• Coronary artery dilation in MIS-C patients mostly resolves within three months of follow-up. Factors associated with coronary artery dilation in MIS-C patients include: male sex, Kawasaki-like phenotype and mesenteric lymphadenitis.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.5), and noncardiac involvement through 6 months after MIS-C.

This cohort study enrolled participants between March 2020 and January 2022 with a follow-up period of 2 years. Participants were recruited from 32 North American pediatric hospitals, and all participants met the 2020 Centers for Disease Control and Prevention case definition of MIS-C.

MIS-C after COVID-19 infection.

Outcomes included echocardiography core laboratory (ECL) assessments of LVEF and maximum coronary artery z scores (zMax); data collection on cardiac and noncardiac sequelae during hospitalization and at 2 weeks, 6 weeks, and 6 months after discharge; and age-appropriate Patient-Reported Outcomes Measurement Information Systems (PROMIS) Global Health Instruments at follow-up. Descriptive statistics, linear regression models, and Kaplan-Meier analysis were used.

Of 1204 participants (median [IQR] age, 9.1 [5.6-12.7] years; 724 male [60.1%]), 325 self-identified with non-Hispanic Black race (27.0%) and 324 with Hispanic ethnicity (26.9%). A total of 548 of 1195 participants (45.9%) required vasoactive support, 17 of 1195 (1.4%) required extracorporeal membrane oxygenation, and 3 (0.3%) died during hospitalization. Of participants with echocardiograms reviewed by the ECL (n = 349 due to budget constraints), 131 of 322 (42.3%) had LVEF less than 55% during hospitalization; of those with follow-up, all but 1 normalized by 6 months. Black race (vs other/unknown race), higher C-reactive protein level, and abnormal troponin level were associated with lowest LVEF (estimate [SE], -3.09 [0.98]; R2 = 0.14; P =.002). Fifteen participants had coronary artery z scores of 2.5 or greater at any time point; 1 participant had a large/giant aneurysm. Of the 13 participants with z scores of 2.5 or greater during hospitalization, 12 (92.3%) had normalized by 6 months. Return to greater than 90% of pre-MIS-C health status (energy, sleep, appetite, cognition, and mood) was reported by 711 of 824 participants (86.3%) at 2 weeks, increasing to 548 of 576 (95.1%) at 6 months. Fatigue was the most common symptom reported at 2 weeks (141 of 889 [15.9%]), falling to 3.4% (22 of 638) by 6 months. PROMIS Global Health parent/guardian proxy median T scores for fatigue, global health, and pain interference improved significantly from 2 weeks to 6 months (fatigue, 56.1 vs 48.9; global health, 48.8 vs 51.3; pain interference, 53.0 vs 43.3; P < .001) and by the 6-week visit were at least equivalent to prepandemic population norms.

Results of this cohort study suggest that although children and young adults with MIS-C can have severe disease during the acute phase, most recovered quickly and had a reassuring midterm prognosis.

To elucidate how the clinical presentation of Pediatric Inflammatory Multisystem Syndrome temporally associated with Severe Acute Respiratory Syndrome-related Coronavirus 2 (PIMS-TS) was influenced by the successive variants of concern (VOC) and patient age.

A nationwide PIMS-TS registry was established in Germany in May 2020, shortly after the first cases were described in the US and United Kingdom. The registry captured information on patient characteristics, clinical course, laboratory findings, imaging, and outcome. All pediatric hospitals in Germany, along with one in Austria, were invited to participate. Between March 18, 2020, and April 30, 2023, 920 cases were reported.

By examining a combination of data on clinical features, laboratory findings, treatment, imaging results, and outcomes, our analysis demonstrated disease severity to have continuously declined over the course of the Wildtype, Alpha, Delta, and Omicron waves. Based on clinical symptoms, laboratory and diagnostic findings, and intensive care unit admission rates, older children, irrespective of the related VOC, were shown to experience more severe, acute PIMS-TS; however, they had lower rates of coronary aneurysm.

During the course of COVID-19 pandemic, as each new VOC emerged, PIMS-TS lessened in severity. In parallel, older children came to experience more debilitating disease.

Multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19, is frequently associated with cardiac involvement. Although most affected children recover, the extent and duration of myocardial abnormalities remain uncertain. This study evaluates mid-term cardiac function in MIS-C patients, with and without cardiac involvement, using transthoracic echocardiography (TTE) and speckle-tracking echocardiography (STE).

This case-control study (2022-2023) included 90 children: 30 with MIS-C and cardiac involvement, 30 with MIS-C without cardiac involvement, and 30 healthy controls. TTE and STE were used to assess left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at diagnosis and at three months, comparing outcomes across groups.

The cardiac involvement group exhibited significantly elevated ferritin and C-reactive protein levels (P = 0.006 and P = 0.017, respectively) and a higher prevalence of troponin positivity (56.67% vs. 20%, P = 0.009). At baseline, these patients had markedly reduced LVEF (56.5 ± 4.3) and GLS (-21.6 ± 3.21) compared to healthy controls (LVEF: 68.2 ± 5.21; GLS: -24.8 ± 1.48; both P < 0.001). Notably, the basal segment showed significant longitudinal strain reduction (-18.75 ± 3.89 vs. -23.58 ± 0.27, P = 0.027), while differences in the apical and mid segments were not significant. By three months, LVEF (69 ± 4.21, P = 0.53) and GLS (-24.13 ± 2.39, P = 0.17) normalized. Heart failure and coronary artery brightness resolved in all affected patients, and most structural abnormalities improved; only two cases exhibited persistent mild left ventricular dilation. Regional strain analysis at follow-up revealed values comparable to those of healthy controls across all segments.

Cardiac dysfunction in MIS-C largely resolves within three months, with LVEF and GLS returning to normal. However, persistent myocardial abnormalities in a few cases highlight the need for long-term cardiac monitoring to detect and manage potential sequelae.

The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year's worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year's edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year's Statistical Update.

Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

We compared the quantity of labs ordered in selected hospitalized children throughout the COVID-19 pandemic. Utilization of X-ray, magnetic resonance imaging (MRI), echocardiograms, and electrocardiograms (ECG), length of stay (LOS) and timing of antibiotics were secondary outcomes. Retrospective cohort study of patients >60 days to <22 years with cellulitis, pneumonia, and urinary tract infections discharged from hospital medicine March 2018 to February 2020 (pre-) March 2020 to February 2022 (peak) and March 2022 to April 2023 (post peak). Fisher-Freeman-Halton exact test was performed for categorical variables. Kruskal-Wallis test compared continuous variables. Patients admitted peak pandemic incurred more labs and ECGs and fewer MRIs and X-rays. There were no differences in echocardiograms, LOS, or timing of antibiotics. While lab utilization returned to pre-pandemic levels, increased ECG use continued. Increased lab and ECG utilization was observed in patients with certain bacterial infections during the peak of the pandemic, likely reflective of diagnostic uncertainty.

The aim of this study was to analyze data on pediatric cases of COVID-19 admitted to a tertiary referral hospital in northwest Greece.

A retrospective analysis was conducted on the most common clinical manifestations and laboratory findings, stratified by age group and SARS-CoV-2 strain.

A total of 254 children were hospitalized, with a mean age of 4.5 years. Underlying conditions were present in 10.2% of cases; two children required pediatric intensive care unit (PICU) admission, and one child died. The most common hematological manifestations, in general, were neutropenia (30%) and lymphopenia (23%), whereas the findings varied when the children were stratified by age group. Eight children developed multisystem inflammatory syndrome (MIS-C), with the most common findings being anemia (75%), lymphopenia (50%), and thrombocytopenia (25%). Analysis of the SARS-CoV-2 strains revealed the proportions of the dominant strain over time. Fever was the predominant symptom across all strains, particularly in the Omicron group, which also had a high incidence of gastrointestinal symptoms. The longest hospital admission occurred in children with the Omicron strain, followed by the Wuhan, Alpha, and Delta strains.

Fever was the most consistent symptom across all age groups and virus strains. The most common hematological manifestations were neutropenia (30%) and lymphopenia (23%). The Omicron strain was associated with the longest hospital stay.

Little is known about the dermatologic manifestations of multisystem inflammatory syndrome in children (MIS-C) in children and adolescents.

We sought to describe the demographic background, key clinical features, and the clinical consequences of developing rash manifestations in MIS-C patients at Texas Children's Hospital.

Descriptive retrospective cohort study of 290 hospitalized eligible patients between May 2020 and April 2022.

Among MIS-C patients, 51% exhibited a rash. We found that younger children (8.62 vs 9.49 years of age, P = .006) and White children (P = .002) had a higher likelihood of developing a rash in association with MIS-C. Additionally, patients without a rash had increased maximum troponin levels (0.11 ng/mL vs 0.07 ng/mL, P = .02) and a higher incidence of cardiac involvement (83.1% vs 72.3%, P = .03) compared to those with a rash but did not significantly affect the length of hospital stay or clinical course. The most commonly observed rash was an erythematous and maculopapular rash on the trunk and/or extremities.

Rash characteristics were initially described by a variety of physicians in the pediatric primary care services.

Rash manifestations in MIS-C patients are associated with lower cardiac involvement and decreased troponin levels.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but certain baseline characteristics can increase the risk of moderate to severe disease. The following article will provide an overview of the clinical manifestations of coronavirus disease 2019 in children, including the post-infectious phenomenon called multisystem inflammatory syndrome in children. Currently available treatment and prophylaxis strategies will be outlined, with the caveat that new therapeutics and clinical efficacy data are constantly on the horizon.

The rapid development and deployment of mRNA and non-mRNA COVID-19 vaccines have played a pivotal role in mitigating the global pandemic. Despite their success in reducing severe disease outcomes, emerging concerns about cardiovascular complications have raised questions regarding their safety. This systematic review critically evaluates the evidence on the cardiovascular effects of COVID-19 vaccines, assessing both their protective and adverse impacts, while considering the challenges posed by the limited availability of randomized controlled trial (RCT) data on these rare adverse events. In adherence to PRISMA 2020 guidelines, we conducted a systematic review using the Scopus database, incorporating articles published from January 2020 to July 2024. Our search included terms related to COVID-19 vaccines and cardiovascular conditions. We selected relevant studies from case-control studies, cohort studies, and clinical trials, while excluding descriptive analyses, cross-sectional studies, and conference reports. Case reports were also included due to the limited availability of extensive RCT data on the rare cardiovascular adverse events associated with COVID-19 vaccines. Of the 6037 articles initially screened, 410 were assessed in detail and 175 studies were ultimately included. The review identified a variety of cardiovascular adverse effects associated with COVID-19 vaccines. mRNA vaccines were primarily linked to myocarditis and pericarditis, particularly in younger males, with lower cardiac risks compared to COVID-19 infection. Adenoviral vector vaccines were associated with thrombosis and thrombocytopenia. Inactivated vaccines had fewer severe cardiovascular reports but still presented risks. Takotsubo cardiomyopathy was most commonly observed following mRNA vaccination. Case reports provided valuable additional insights into these rare events, highlighting clinical presentations and potential risk factors not fully captured by larger epidemiological studies. This review reveals a nuanced cardiovascular risk profile for COVID-19 vaccines, with mRNA vaccines linked to rare myocarditis and pericarditis in young males and a higher incidence of Takotsubo cardiomyopathy in females. Adenoviral vaccines show a notable association with thrombosis. Despite these risks, the benefits of vaccination in preventing severe COVID-19 outcomes outweigh the potential complications, underscoring the importance of continued surveillance, case report documentation, and personalized risk assessment. The inclusion of case reports was critical, as they provided valuable real-world data that complemented the findings from large-scale studies and RCTs.

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.

In this review article, we aim to provide an overview of the pathophysiology, the clinical features, the therapeutic management and prognosis of patients affected by Multisystemic inflammatory syndrome (MIS) with cardiac involvement, focusing on myocarditis and pericarditis.

MIS is a multiorgan hyperinflammatory condition due to a cytokine storm following (within 4-12 weeks) SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection. First described in children, it also affects young adults without comorbidities, predominantly males with highly heterogeneous clinical manifestations, including cardiac involvement. Pericardial and myocardial involvement are prevalent among patients affected by MIS leading to different clinical manifestations including myocarditis with arrhythmias, acute heart failure and cardiogenic shock that significantly affect the patient's prognosis. The heterogeneity of its clinical features and the significant overlap with other hyperinflammatory diseases make the diagnosis particularly challenging. Moreover, the evidence on the efficacy of pharmacological treatments targeting the hyperinflammatory response is scarce, as well as data on long-term prognosis.

This study aimed to evaluate pathological findings on abdominal ultrasonography upon admission of children diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) that were associated with a more severe disease course and the need for intensive care unit (ICU) admission. This retrospective and observational study was conducted between March 2020 and May 2022. Abdominal ultrasonography findings were evaluated in children diagnosed with MIS-C associated with SARS-CoV-2. Ultrasound examinations were conducted within the first 24 h following hospital admission. Clinical severity was categorized as mild-moderate or severe based on the highest clinical severity score observed at any point during hospitalization, using the criteria of dehydration, oxygen or inotropic requirements, cardiac involvement, and respiratory support. The indications of ICU admission were decreased ejection fraction, pulmonary involvement, and any signs of shock. We compared the presence of any individual ultrasonography findings with clinical severity and the need for ICU admission. Multivariable logistic regression analysis was performed to identify independent sonographic predictors of clinical severity and ICU admission. A total of 70 children were included in the study, 16 of whom (23%) were categorized as having severe diseases. ICU admission was required for 14 children (20%), 13 of whom had severe disease. Notably, three children with severe clinical scores did not require ICU admission. The most common ultrasonography findings were intra-abdominal free fluid (41%), hepatomegaly (36%), splenomegaly (33%), mesenteric inflammation (21%) and mesenteric lymphadenopathy (%19). Intra-abdominal free fluid (p < 0.001; OR = 18.20; 95% CI, 3.69-89.86), mesenteric inflammation (p < 0.001; OR = 10.29; 95% CI, 2.80-37.83), mesenteric lymphadenopathy (p = 0.007; OR = 6.22; 95% CI; 1.69-22.88), and hepatosplenomegaly (p = 0.039; OR = 3.89; 95% CI, 1.15-13.17) were substantially associated with severe clinical outcomes. Intra-abdominal free fluid (p < 0.001; OR = 13.76; 95% CI, 2.77-68.29) and hepatosplenomegaly (p = 0.002; OR = 8.00; 95% CI, 2.19-29.25) were significantly more common in children who required ICU admission. Multivariable logistic regression analysis revealed that intra-abdominal free fluid was an independent predictor of severe disease (p = 0.026; OR = 7.41; 95% CI, 1.28-43.00) and ICU admission (p = 0.007; OR = 9.80; 95% CI, 1.88-51.04).

Abdominal ultrasonography findings may indicate clinical severity in children with MIS-C. Intra-abdominal free fluid strongly correlates with severe clinical outcomes and the need for intensive care.

• Abdominal ultrasonography findings in children with MIS-C are non-specific and include intra-abdominal free fluid, mesenteric lymphadenopathy, and hepatosplenomegaly. • MIS-C is associated with significant systemic inflammation and can present with a variety of extracardiac symptoms, often overlapping with acute abdominal conditions.

• Intra-abdominal free fluid on ultrasonography is strongly associated with severe clinical outcomes and the need for ICU admission in MIS-C patients • This study identifies intra-abdominal free fluid as an independent sonographic predictor of disease severity and intensive care needs, emphasizing the importance of early abdominal ultrasonography in MIS-C management.

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition occurring after SARS-CoV-2 infection in children under 21 years of age. Children (5-17 years) with MIS-C meeting the Centers for Disease Control (CDC) case definition were reported via California's passive disease surveillance system. Incidence of MIS-C was compared in unvaccinated and Pfizer-BioNTech vaccinated children aged 12-17 and 5-11 years. In the 12-17 year-old age group, there were 66 new cases among 872,936 unvaccinated children and 7 new cases among 2,117,575 vaccinated children. In the 5-11 year-old age group, there were 51 new cases among 2,113,725 unvaccinated children and 9 new cases among 1,221,293 vaccinated children. Compared with vaccinated children, the incident rate ratio of MIS-C was higher among unvaccinated children in both the 12-17-year-old group (22.9, 95 % confidence interval [CI]: 10.5-49.8, p < 0.0001) and the 5-11-year-old group (3.3, 95 % CI: 1.6-6.7, p = 0.0004). While MIS-C is rare, our results suggest that vaccination with the Pfizer-BioNTech vaccine is protective against MIS-C.

COVID-19 pandemic research efforts have mainly focused on adults, but data in paediatric populations are sparse.

We used the German nationwide-inpatient-sample analysing all hospitalized children ≤18 years with confirmed COVID-19-diagnosis in Germany during the year 2020, stratified for intensive care unit (ICU) admission.

Overall, 3360 hospitalization-cases of children ≤18 years with COVID-19-infection were diagnosed in Germany 2020 (median age 7.0 [IQR 0.0-15.0] years, 49.8 % female); among them 4.3 % were admitted on an ICU. In-hospital death occurred in five patients with and three without ICU admission (3.5 % vs. 0.1 %, P < 0.001) and ICU admission was independently associated with increased case-fatality (OR 21.573 [95%CI 4.191-111.044], P < 0.001). Obesity (OR 3.419 [95%CI 1.300-8.993], P = 0.013), diabetes mellitus (OR 6.929 [95%CI 3.327-14.432], P < 0.001), pneumonia (OR 7.373 [95%CI 4.823-11.271], P < 0.001), acute respiratory distress syndrome (ARDS) (OR 48.058 [95%CI 11.689-197.588], P < 0.001) and multisystem inflammatory syndrome caused by COVID-19 (OR 9.573 [95%CI 3.036-30.191], P < 0.001), heart failure (OR 64.509 [95%CI 24.462-170.121], P < 0.001), myocarditis (OR 4.682 [95%CI 1.278-17.149], P = 0.020), acute and/or chronic kidney failure (OR 7.946 [95%CI 3.606-17.508], P < 0.001), cancer (OR 5.220 [95%CI 2.599-10.485], P < 0.001) and liver diseases (OR 5.501 [95%CI 2.177-13.899], P < 0.001) were associated with an ICU admission.

Proportion of hospitalized paediatric COVID-19-patients admitted on ICU in Germany was low with 4.3 % accompanied by 3.5 % case-fatality rate. Independent factors for ICU admission comprised cardio-vascular risk factors, comorbidities, and complications of COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

There is growing understanding that Social Determinants of Health (SDH) impact on the outcomes of different pediatric conditions. We aimed to determine whether SDH affect the severity of MIS-C.

Retrospective cohort study, 2021-2023. Children and adolescents with MIS-C younger than 18 years of age fulfilling the MIS-C CDC definition within the REKAMLATINA network were invited to participate. We assessed the impact of SDH on the risk of children with MIS-C to be diagnosed with shock, need of inotropes, respiratory support, transfusion, and death.

Two hundred and seventy seven patients from 30 centers in 13 countries were included. Of them, 241 children from the four most-represented countries were included in the final analysis. Food insecurity, higher distance from a health center, not possessing a private vehicle to transport the patient to hospital, and having a home in poor condition, were associated with low LVEF, need of transfusion, shock, and need for respiratory support, when controlling for age, BMI, and ethnicity. The Score of Social Disadvantage was associated with Shock (OR: 1.35, P: 0.011, 95% CI: 1.07-1.71), Respiratory support (OR: 1.39, P: 0.005, 95% CI: 1.1-1.75), Transfusion (OR: 1.63, P0.013, 95% CI 1.1-2.41), but not death (OR: 0.76, P: 0.38, 95% CI: 0.41-1.40).

Among a large cohort of Latin American children with MIS-C, SDH negatively affect outcomes. These findings reinforce the need for better investigation of the role of SDH in MIS-C and other inflammatory conditions and may guide public health interventions.

To investigate trends in the diagnosis of venous thromboembolism (VTE) and arterial ischemic stroke (AIS), and examine the use of pharmacological thromboprophylaxis during the COVID-19 pandemic.

This retrospective cohort study used the Pediatric Health Information Systems database to investigate patients admitted to a participating hospital between January 1, 2018, and December 31, 2021. International Classification of Diseases, 10th edition codes were used to identify VTE, AIS, and COVID-19. Pharmacy billing codes were used to investigate pharmacological thromboprophylaxis use.

1 759 701 unique patients underwent 2 234 135 inpatient admissions. Rate of VTE increased from 84 cases per 10 000 admissions in 2018-2019 to 108 cases per 10 000 admissions in 2020-2021, representing a 28.6% increase (P < .001). In contrast, the rate of AIS remained stable through the study period. When compared with 2018-2019, children diagnosed with VTE during 2020-2021 had longer hospitalizations and were more likely to be admitted to the intensive care unit. When analysis was limited to 2020-2021, a diagnosis code of COVID-19 was associated with a 1.35-fold (95% CI: 1.24-1.45) increase in the odds of VTE diagnosis, but not AIS. Use of pharmacologic thromboprophylaxis increased from 1.5% of hospitalizations in 2018-2019 to 3.0% of hospitalizations in 2020-2021 (P < .001). When evaluating thromboprophylaxis during 2020-2021, a diagnosis code for COVID-19 was associated with an 11-fold (95% CI: 10.86-11.49; P < .001) increase in the utilization of pharmacological thromboprophylaxis.

This study found an increase in the rate of VTE among hospitalized children during the pandemic. A diagnosis of COVID-19 was associated with a modest increase in odds of VTE diagnosis, which occurred despite increased use of pharmacological thromboprophylaxis.

Given the challenges in diagnosing children with long COVID, we sought to explore diagnostic practices and preferences among clinicians.

A ten-question survey assessed pediatric providers' clinical decision making for identifying and evaluating long COVID in children. Of the 120 survey respondents, 84 (70%) were physicians, 31 (26%) nurse practitioners, and 5 (4%) physician assistants.

The most common categories of symptoms identified as raising suspicion for long COVID in children included cardiopulmonary symptoms, selected by 119 (99%) of pediatric providers, and neurocognitive symptoms, selected by 118 (98%) of providers. However, there was more ambiguity on the primary feature of long COVID, with providers selecting a range of key symptoms. Of all physical exam findings, postural orthostatic tachycardia, was most suggestive of long COVID [identified by 49 (41%) of pediatric providers], whereas one-third of providers reported no specific identifiable exam finding.

Pediatric providers report variable decision making in the clinical evaluation of long COVID, with patient demographics and clinical factors impacting whether a diagnosis of long COVID is considered. This variation in diagnosing pediatric long COVID reflects ambiguity in the definition of long COVID in children and the absence of clinical guidelines to support providers in the identification of disease and treatment. This study highlights an area of need for future clinical advances in pediatric long COVID.

PECOS is an ongoing study aimed to characterize long-term outcomes following pediatric SARS-CoV-2 infection.

This is a cross-sectional analysis of infected and uninfected cohorts at baseline. Participants (0-21 years) with laboratory-confirmed SARS-CoV-2 infection were enrolled as infected. Uninfected were defined as individuals without history or laboratory evidence of SARS-CoV-2 infection. Outcome measures included demographics, medical history, review of symptoms, physical exam, cardiopulmonary evaluation and validated psychological and developmental surveys. Primary outcomes were cohort comparisons for abnormalities on all measures.

654 participants (541 infected, 113 uninfected) completed baseline visits by June 30, 2023. Infected participants were more likely to report constitutional (OR: 2.24), HEENT (OR: 3.74); respiratory (OR: 2.41), or gastrointestinal (OR: 2.58) symptoms. Infected had worse scores in domains of Pain, Fatigue, Global Health, Physical and Cognitive functioning, Mobility and Sleep disturbances when compared to uninfected controls using Patient Reported Outcomes. Cardiopulmonary findings were similar among cohorts.

The first report of this ongoing longitudinal study demonstrates that infected participants were more likely to report symptoms compared to uninfected controls, which may affect performance and quality of life of these individuals. Longitudinal data will increase understanding of long-term effects of SARS-CoV-2 infection in children.

gov Identifier: NCT04830852 IMPACT: This study establishes a large, diverse, prospective, longitudinal, multi-center cohort of children with history of SARS-CoV-2 infection compared to an uninfected cohort to be followed for 3 years. Cross-sectional cohort analysis at study entry showed infected participants were more likely to report constitutional, respiratory, and GI symptoms compared to uninfected controls. Infected participants were more likely to have significantly worse parent-reported performance in 6 of 10 Patient Reported Outcome Measures domains. Continued study of this cohort will help identify clinical sequelae of COVID-19, characterize the immune response to SARS-CoV-2 infection, and identify potential genetic/immunologic factors associated with long-term outcomes.

Background: Macrophage activation syndrome (MAS) can be regarded as a key factor determining the severity of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C), and often requires treatment in the intensive care unit (ICU) to avoid life-threatening complications. No reputable specific criteria for the diagnosis of MAS in MIS-C patients have yet been identified, and criteria currently used for the diagnosis of hemophagocytic syndromes, such as HLH-2004, MAS-2005, and MAS-2016, are not sufficient for MAS in MIS-C. Our goal in this study was to work out the criteria for the early diagnosis of MAS in MIS-C. Methods: One hundred and sixty-six (166) patients with MIS-C were assessed retrospectively. The two most experienced experts independently identified patients with MAS. The patients were divided into three cohorts: MAS (n = 19), without MAS (n = 78), and probable MAS (n = 67). The latter included patients diagnosed with MAS by only one expert, and it was excluded from the analysis. Results: The age of patients with MAS was much higher, and they more frequently had edematous syndrome, hypotension and/or shock, splenomegaly, and CNS involvement. In their blood tests, thrombocytopenia, hypoalbuminemia, and hypertriglyceridemia occurred more often. The level of biomarkers of inflammation, such as ferritin, CRP, troponin, AST, and ALT, was also higher in this group. Increased fibrinogen and D-dimer were also found, demonstrating hypercoagulation in the MAS-MIS-C group. We chose 21 continuous and categorical variables with statistical significance, out of which 2-ferritin > 469 μg/L or platelets < 114 × 109/L-allowed us to discriminate MAS patients. Conclusions: Ferritin > 469 μg/L or platelets < 114 × 109/L can be regarded as key signs to differentiate MAS in MIS-C patients with a sensitivity of 100% and specificity of 94.9%, and they can be used along with other diagnostic methods.

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on nuclear factor-κB signaling. Nine rare, potentially deleterious variants were found in 8 of 21 patients, located in the IL17RC, IFNA10, or NLRP12 gene. Unlike the wild type NLRP12 protein, which inhibits nuclear factor-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C.

Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.

Multilayer strain magnetic resonance imaging (MRI) analysis offers detailed insights into myocardial mechanics and cardiac function by assessing different layers of the heart muscle, enabling a comprehensive understanding of cardiac involvement.

This study aims to explore cardiac strain differences between patients with multisystem inflammatory syndrome and a control group at medium-term follow-up, utilizing a layer-specific cardiac magnetic resonance imaging (CMR) approach.

In this retrospective study, patients with multisystem inflammatory syndrome in children (MIS-C) and a group of controls who had undergone cardiac magnetic resonance (CMR) imaging were selected and included. CMR was performed 30 days after discharge (range 34-341 days) for MIS-C patients. TrufiStrain research prototype software (Siemens Healthineers AG, Erlangen, Germany) was used for automated myocardial segmentation and strain calculation, to measure radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) at the epicardial, mid-wall, and endocardial levels. Statistical analysis included Shapiro-Wilk tests, Student t-tests, and Mann-Whitney U tests, ANOVA, and regression analysis, maintaining a significance level of α = 0.05.

The study cohort consisted of 32 MIS-C patients (≤ 18 years; 14 females) and 64 control participants (≤ 18 years; 24 females). Median interval to CMR post diagnosis was 142 days (range 34-341) with normal CMR findings for all patients. The mean age of the two groups was similar (MIS-C: 14.2 years; controls: 14.1 years, P = 0.49). There were no significant differences in height (MIS-C: 164.7 cm; controls: 163.9 cm, P = 0.84), weight (MIS-C: 68.2 kg; controls: 59.4 kg, P = 0.11), or body surface area (MIS-C: 1.7 m2; controls: 1.7 m2, P = 0.41). Global strain measurements showed no significant differences between the groups (global LS MIS-C patients - 16.2% vs - 15.7% in controls (P = 0.23); global RS 27.8% in MIS-C patients vs 29.5% in controls (P = 0.35); and global CS - 16.7% in MIS-C patients vs - 16.8% in controls (P = 0.92)). Similarly, layer-specific strain analysis across the endocardial (LS values of - 17.7% vs - 16.8% (P = 0.19), RS of 23.1% vs 24.8% (P = 0.25), and CS of - 19.9% vs - 19.9% (P = 0.92)), epicardial (LS - 14.9% vs - 14.5% (P = 0.31), RS of 31.2% vs 33.1% (P = 0.29), and CS of - 14.1% vs - 14.2% (P = 0.75)), and midmyocardial (LS - 16.5% vs - 16.3% (P = 0.18), RS 29.3% vs 31.8% (P = 0.31), and CS - 17.0% vs - 17.2% (P = 0.95)) levels revealed no significant disparities. The only notable finding was the reduced apical radial strain in MIS-C patients compared to controls (global RS MIS-C 12.4% vs 17.4% in controls, P = 0.03; endocardium RS MIS-C 4.9% vs 10.31% in controls, P = 0.01; epicardial RS MIS-C 17.7% vs 22.6% in controls, P = 0.02; and midmyocardium RS MIS-C 12.5% vs 17.9% in controls, P = 0.02).

This study demonstrates that MIS-C does not significantly impact global or layer-specific myocardial strain values, as assessed by CMR, compared to a control group. The lower apical radial strain in MIS-C patients indicates a potential localized myocardial involvement.

Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan.

Using a case reporting form, a nationwide registry was created between November 2020 and March 2023, involving 2,080 facilities throughout Japan. We prospectively and retrospectively enrolled patients with MIS-C. The primary outcomes were the number and incidence rates of children with MIS-C. The secondary outcomes included clinical features, such as KD phenotype, organ involvement, shock, intensive care unit admission, and coronary artery lesions.

Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7 years). The overall incidence rate was estimated to be 1·5 per 100,000 COVID-19 cases, exhibiting a decline as the COVID-19 pandemic progressed, from 12·3 cases (Pre-Delta) to 1·3 cases (Omicron); 80% of MIS-C cases occurred during the Omicron variant predominant period, and 72% of children with MIS-C met the KD criteria. Cardiovascular (88%) and gastrointestinal (90%) involvement were frequent. In Japan, MIS-C cases showed comparatively less severe clinical features, with shock in 29% and admission to the intensive care unit in 12% of cases. Coronary artery lesions were identified in 15 cases (11·6%), irrespective of the presence of shock. No fatalities were reported.

The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features.

Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS).

We aimed to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes.

We recruited children who sought care at the emergency department with fever for ≥3 days. We performed immune profiling using Olink proximity extension assay and flow cytometry. We compared the findings with cases of HLH, MAS, Kawasaki disease (KD), and multisystem inflammatory syndrome in children (MIS-C).

We enrolled 352 febrile patients and studied 110 cases of confirmed common viral infections. We found that Epstein-Barr virus (EBV) uniquely triggered high levels of multiple cytokines (IL-18, IL-27, TNF, FLT3 ligand, and lymphotoxin alpha) and IFN-γ-induced chemokines (CXCL9/10/11 and CCL19). These patterns are similar to the hyperinflammatory response associated with HLH/MAS but are less consistent with the findings in KD and MIS-C. Flow cytometry analysis revealed that CD38+HLA-DR+ T lymphocytes, which are pathogenic cells responsible for IFN-γ production in HLH/MAS, are vastly expanded in patients with acute EBV infection. Cell sorting identified CD38+HLA-DR+ T cells as atypical lymphocytes that are classically associated with acute EBV infection.

This work broadens our understanding of common viral infections in children and provides an immunologic basis for the link between EBV infection and HLH/MAS.

This study aimed to evaluate the range of clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C) with COVID-19 in a tertiary children's hospital in Northwest Iran during 2020-2022. According to the CDC guidelines, this cross-sectional study included 300 pediatric patients diagnosed with MIS-C. Data were collected retrospectively from medical records, focusing on symptoms, organ involvement, laboratory findings, and outcomes. Statistical analysis was performed using SPSS software, with significance set at p-values <0.05. The study population had a median age of 3 years, with a slight male predominance (57.3%). The most affected systems in MIS-C disease were hematological (87%), gastrointestinal (85%), and respiratory (67%). Laboratory analysis highlighted elevated inflammatory markers such as D-dimer (83.3%), ferritin (71.4%), and CRP (49.7%). Abnormal urinalysis was observed in 151 patients (50.3%), with glucosuria in 83 cases (27.7%) and proteinuria in 29 cases (9.7%). The study found a significant correlation between cardiovascular issues and elevated blood platelets, ESR, CRP, and troponin levels (P ≤ 0.01) but not with ferritin, albumin, or D-dimer levels. Also, the examination of disease outcomes in this study revealed that 81.7% of MIS-C patients were isolated during their hospital stay, 18.3% needed ICU care, and 1% died in hospital. We have presented an experience with distinct clinical and laboratory manifestations in MIS-C. Given the lower median age in this study compared to previous studies, reporting clinical and laboratory manifestations of MIS-C in pediatrics with a younger age is valuable for the diagnosis and treatment course. Some laboratory factors were risk factors for cardiovascular involvement, and consequently, echocardiography is recommended in MIS-C patients with these laboratory indications. Given the lack of a specific diagnostic test for this emerging disease, studies focusing on investigating clinical symptoms and findings are valuable.

The epidemiology of coronavirus disease 2019 (COVID-19) in children has evolved throughout the pandemic, with initially low infection rates rising significantly as a result of the emergence of the more transmissible Omicron variant. Adolescents, children from ethnic minorities and lower-income households, and those with obesity are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The immune response in children leads to milder symptoms compared to adults, with fever and cough being most frequent; tough symptoms vary by SARS-CoV-2 variant and age. Diagnostic methods to confirm current or past infection include reverse transcription PCR, rapid antigen tests, and serology. Treatment is mainly supportive, with antivirals and glucocorticoids reserved for severe cases. While serious conditions like multisystem inflammatory syndrome in children and other post-COVID-19 conditions are rare, they require careful management. Vaccination has proven effective in reducing severe disease and protecting against post-COVID-19 conditions. Continued surveillance, including wastewater monitoring and universal or pooled testing, remains crucial for controlling community spread. Key questions remain regarding the duration and quality of immunity after reinfection or vaccination, the impact of coinfections, and optimal treatment protocols for different pediatric populations.