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.

Multisystem inflammatory syndrome in children (MIS-C) is associated with cardiac involvement in 67%-80% of cases. Cardiac symptoms often normalize rapidly after treatment, but few studies are available on the long-term cardiac effects.

Our study evaluated the cardiac functions of 40 patients diagnosed with MIS-C between August 2021 and November 2022. Conventional echocardiography (ECHO), electrocardiography (ECG), speckle tracking echocardiography (STE), and cardiac MR were performed at the time of diagnosis and 3-nd 6-month follow-up.

Of the 40 patients, 65% (26) were male and 35% (14) were female. The average age at diagnosis was 8.37 ± 4.59 years (range 2-17). Systolic dysfunction was observed in 11(27.5%) patients on conventional ECHO; two patients (5%) required extracorporeal membrane oxygenation (ECMO) support. All patients showed rapid normalization of conventional ECHO findings with treatment. At the 3-month follow-up, no abnormalities in left ventricle ejection fraction (LVEF) and fractional shortening (LVFS) were detected on conventional ECHO, but STE revealed contraction abnormalities in the mid-inferior and apical inferior regions of the two-chamber view, the basal inferoseptal and mid-anterolateral regions of the four-chamber view, though improvement was noted compared to initial findings. At the 6-month follow-up, only a minimal contraction abnormality persisted in the two-chamber mid-inferior region. Cardiac MR performed at 1 year in 8 (20%) patients revealed normal results.

The cardiac effects of MIS-C were found to improve rapidly with treatment. STE is a valuable tool for detecting and monitoring regional contraction abnormalities in MIS-C patients.

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.

The VIPS (Vascular Effects of Infection in Pediatric Stroke) II prospective cohort study aimed to better understand published findings that common acute infections, particularly respiratory viruses, can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through enrollment, creating an opportunity to assess its impact.

Twenty-two sites (North America, Australia) prospectively enrolled 205 children (aged 28 days to 18 years) with AIS from December 2016 to January 2022, including 100 cases during the COVID-19 pandemic epoch, defined here as January 2020 to January 2022. To assess background rates of subclinical infection, we enrolled 100 stroke-free well children, including 39 during the pandemic. We measured serum SARS-CoV-2 nucleocapsid total antibodies (present after infection, not vaccination; half-life of 3-6 months). We assessed clinical infection via parental interview.

The monthly rate of eligible AIS cases declined from spring through fall 2020, recovering in early 2021 and peaking in the spring. The prepandemic and pandemic cases were similar except pandemic cases had fewer clinical infections in the prior month (17% versus 30%; P=0.02) and more focal cerebral arteriopathy (20% versus 11%; P=0.09). Among pandemic cases, 26 of 100 (26%) had positive antibodies, versus 4 of 39 (10%) of pandemic-era well children (P=0.04). The first SARS-CoV-2 positive case occurred in July 2020. Ten of the 26 (38%) positive cases had a recent infection by parental report, and 7 of those 10 had received a diagnosis of COVID-19. Only 1 had multisystem inflammatory syndrome in children. Median (interquartile range) nucleocapsid IgG total levels were 50.1 S/CO (specimen to calibrator absorbance ratio; 26.9-95.3) in the positive cases and 18.8 (12.0-101) in the positive well children (P=0.33).

The COVID-19 pandemic may have had dual effects on childhood AIS: an indirect protective effect related to public health measures reducing infectious exposure in general, and a deleterious effect as COVID-19 emerged as another respiratory virus that can trigger childhood AIS.

Adult solid organ transplant recipients (SOTRs) have decreased responsiveness to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination and higher incidence of infection, but there are few data on the serological response in pediatric SOTR. The aim of this study was to determine serological response to SARS-CoV-2 vaccination in pediatric liver (LT) and kidney transplant (KT) recipients and compare it with adult SOTR.

A European, prospective, multicenter study was performed. Samples were taken at 7 and 32 wk following COVID-19 vaccination and serological endpoints were measured by ELISA.

A total of 42 pediatric (16 post-LT and 26 post-KT) and 117 adult (all post-LT) were included. All pediatric participants and 94% adult participants received mRNA vaccines. Paediatric SOTR patients had significantly higher anti-Spike IgG levels than adult participants at week 7 (114 220.7 [59 285.92-220 058.55] versus 8756.7 [5643.69-13 586.71], P < 0.0001) and week 32 (46 113.2 [10 992.91-193 436.14] versus 8207.0 [3561.20-18 913.43], P = 0.0032). No significant difference in week 7 anti-Spike IgG response was found between pediatric LT and KT (129 434.4 [51 888.64-322 869.69] versus 105 304.5 [39 910.20-277 849.50], P = 0.9854). No differences were seen between children and adults in the rate of decline of anti-Spike IgG between weeks 7 and 32 (P = 0.8000). Male sex and hemolytic-uremic syndrome or postischemic kidney disease were associated with lower anti-Spike IgG levels at week 7 in pediatric SOTR.

Paediatric SOTR demonstrate greater SARS-CoV-2 vaccine responses than comparable adult SOTR patients. These data support efficacy and safety of SARS-CoV-2 vaccination in child SOTR and may alleviate vaccine hesitancy in this patient group.

We demonstrate an approach that integrates biomarker analysis with machine learning to identify protein signatures, using the example of SARS-CoV-2-induced Multisystem Inflammatory Syndrome in Children (MIS-C).

We used plasma samples collected from subjects diagnosed with MIS-C and compared them first to controls with asymptomatic/mild SARS-CoV-2 infection and then to controls with pneumonia or Kawasaki disease. We used mass spectrometry to identify proteins. Support vector machine (SVM) algorithm-based classification schemes were used to analyze protein pathways. We assessed diagnostic accuracy using internal and external cross-validation.

Proteomic analysis of a training dataset containing MIS-C (N=17), and asymptomatic/mild SARS-CoV-2 infected control samples (N=20) identified 643 proteins, of which 101 were differentially expressed. Plasma proteins associated with inflammation and coagulation increased and those associated with lipid metabolism decreased in MIS-C relative to controls. The SVM machine learning algorithm identified a three-protein model (ORM1, AZGP1, SERPINA3) that achieved 90.0% specificity, 88.2% sensitivity, and 93.5% area under the curve (AUC) distinguishing MIS-C from controls in the training set. Performance was retained in the validation dataset utilizing MIS-C (N=17) and asymptomatic/mild SARS-CoV-2 infected control samples (N=10) (90.0% specificity, 84.2% sensitivity, 87.4% AUC). We next replicated our approach to compare MIS-C with similarly presenting syndromes, such as pneumonia (N=17) and Kawasaki Disease (N=13) and found a distinct three-protein signature (VWF, SERPINA3, and FCGBP) that accurately distinguished MIS-C from the other conditions (97.5% specificity, 89.5% sensitivity, 95.6% AUC). We also developed a software tool that may be used to evaluate other protein pathway signatures using our data.

We used MIS-C, a novel hyperinflammatory illness, to demonstrate that the use of mass spectrometry to identify candidate plasma proteins followed by machine learning, specifically SVM, is an efficient strategy for identifying and evaluating biomarker signatures for disease classification.

Fulminant presentations of acute myocarditis can predict cardiac functional and patient outcomes. This longitudinal study compared pediatric cohorts with fulminant Multisystem Inflammatory Syndrome-related myocarditis (MISCM) vs non-COVID-19 viral myocarditis (VM) to test the hypothesis that the adverse left ventricular (LV) remodeling rather than the phenotype of presentation predicts clinical outcomes. This is a retrospective analysis of 54 children with MISCM (age 6 ± 4 years, weight 32.5 ± 24.6 kg, male 44%) and 26 children with VM (age 3.8 ± 4.8 years, weight 17.7 ± 17.7 kg, male 56%) on hospitalization and one-year follow-up. VM patients exhibited acute LV remodeling, but MISC patients did not (LV end-diastolic dimension z score 2.05 ± 2.50 vs 0.04 ± 1.10, p = 0.00). Compared to the MISCM, VM patients had severe LV systolic and diastolic dysfunction (ejection fraction 54.6% vs 39.9%, four-chamber longitudinal strain - 15.6% vs - 8.7%, and left atrial strain 25.5% vs 13.9% p = 0.000), increased need for mechanical circulatory support (39% vs 7%), 2 mortalities, one cardiac transplant, and stage C heart failure in the 17 survivors at discharge. Ejection fraction normalized but abnormal segmental four-chamber longitudinal strain persisted in both cohorts with most VM patients remaining on anti-failure treatment at one-year follow-up. Inflammation-mediated acute LV remodeling rather than the phenotype of presentation may determine LV function and patient outcomes. Non-invasive imaging can play a useful role in the assessment of the mechanism of LV remodeling and defining the trajectory of LV function and cardiac outcomes.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that emerged during the COVID-19 pandemic. While most coronary artery abnormalities in MIS-C are transient, the potential for persistent or progressive coronary aneurysms remains unclear. This report presents the long-term follow-up of a pediatric MIS-C case with multiple giant coronary artery aneurysms.

A 4-year-old boy presented with 13 days of persistent fever during the COVID-19 pandemic. MIS-C was diagnosed based on high-grade fever, markedly elevated inflammatory markers, recent SARS-CoV-2 exposure, and coronary artery involvement on echocardiography. The patient showed rapid clinical improvement following treatment with intravenous immunoglobulin, corticosteroids, aspirin, and enoxaparin. Cardiac catheterization at 8 weeks confirmed multiple giant aneurysms in the right and left coronary arteries. He remained asymptomatic and was followed with echocardiography and ECG every 3 months. After 30 months, repeat catheter angiography revealed persistent giant aneurysms, though with slightly reduced dimensions.

This case highlights that multiple giant coronary artery aneurysms associated with MIS-C may persist even after long-term follow-up, despite clinical and laboratory improvement. It underscores the need for extended cardiac monitoring and prolonged antithrombotic therapy in children with severe coronary involvement.

Multisystem Inflammatory Syndrome in Children is characterized by high rates of acute cardiovascular involvement with rapid recovery of organ dysfunction. However, information regarding long-term sequelae is lacking. We sought to characterize the systolic function and myocardial tissue properties using cardiac magnetic resonance (CMR) imaging in a multicenter observational cohort of Multisystem Inflammatory Syndrome in Children patients.

In this observational cohort study, comprising 32 centers in North America, CMR studies were analyzed by a core laboratory to assess ventricular volumetric data, tissue characterization, and coronary involvement.

A total of 263 CMRs from 255 Multisystem Inflammatory Syndrome in Children patients were analyzed. The mean patient age was 11.4±4.4 years. Most studies were performed at 3 months (33%) or 6 months (45%) after hospitalization. Left ventricular dysfunction was present in 17 (6.7%) of the first CMRs and was never worse than mild. Dysfunction was observed in 4/7 (57%) patients at admission, 5/87 (6.9%) patients at 3 months, and 6/129 (4.6%) patients imaged either at 6 months or 1 year post-hospitalization. Late gadolinium enhancement was present in 2 (0.8%) patients, 1 at 3 months and another at 6 months following hospitalization. Coronary artery dilation was present in 13 of the 174 (7.5%) patients. Nine patients met the Lake Louise criteria for myocarditis (3.5%) at the time of CMR.

In this largest published multiinstitutional longitudinal CMR evaluation of confirmed Multisystem Inflammatory Syndrome in Children patients, the prevalence of ventricular dysfunction and myocardial tissue characterization abnormalities on medium-term follow-up was low. However, a small number of patients had mild residual abnormalities at 6 months and 1 year following hospitalization.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05287412.

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.

Seroprevalence studies play an important role in estimating the number of children infected with SARS-CoV-2. We report SARS-CoV-2 seroprevalence in children seeking medical care for any reason at a free-standing pediatric hospital in Seattle, WA over a 2.5-year period and four distinct pandemic waves. We randomly selected residual serum samples from children and young adults seeking medical care as inpatients and outpatients at Seattle Children's Hospital between June 2020 and December 2022 to test for the presence of anti-nucleocapsid (N) antibodies. Samples were categorized into four distinct pandemic waves based on Washington State epidemiology: Wave 1 (June 2020-October 2020), Wave 2 (November 2020-June 2021), Wave 3 (July 2021-November 2021), and Wave 4 (December 2021-December 2022). Patient characteristics and COVID-19 vaccine status were obtained, and zip codes were used to ascertain the Social Vulnerability Index (SVI). Multivariable Poisson regression models with robust variance estimates were used to examine the relationship between patient characteristics and anti-N-positivity for each wave. Among 8,040 samples from 7,102 patients included in the analyses, seroprevalence rose from 2.4% (95% CI, 2.0%-3.1%) in Wave 1 to 25.5% (95% CI 23.3%-27.8%) in Wave 4 (following the Omicron surge). High SVI, Hispanic ethnicity, or use of government insurance was associated with increased anti-N positivity in most waves. We observed a steady increase in anti-N seroprevalence followed by a sharp increase after the Omicron surge in early 2022. Our data demonstrate the burden of COVID-19 on specific groups with health disparities within our region throughout the pandemic.IMPORTANCEOur results highlight the importance of seropositivity studies as essential tools to provide information on the incidence and prevalence of SARS-CoV-2 seropositivity. Our results also reinforce other reports demonstrating the inequitable burden of COVID-19 on groups with health disparities and that this inequitable burden continued to persist throughout the pandemic, even in a region with high adherence to COVID-19 mitigation efforts. It also highlights SVI's value in identifying communities that must be part of pandemic research, and public health and vaccination strategies.

In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock1 termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion2 and systemic hyperinflammation3. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. 4,5). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein-Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.

While clinical overlap between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) has been evident, information regarding those presenting with shock has been limited. We sought to determine associations with shock within and between diagnosis groups.

The International KD Registry enrolled contemporaneous patients with either KD or MIS-C from 39 sites in 7 countries from January 1, 2020, to January 1, 2023. Demographics, clinical features and presentation, management, laboratory values, and outcomes were compared between the diagnosis and shock groups.

Shock at presentation was noted for 19 of 672 KD patients (2.8%) and 653 of 1472 MIS-C patients (44%; P < 0.001). Within both groups, patients with shock were significantly more likely to be admitted to the intensive care unit, to receive inotropes, and to have greater laboratory abnormalities indicative of hyperinflammation and organ dysfunction, including abnormal cardiac biomarkers. Patients with KD and shock had a greater maximum coronary artery z score (median +2.62) vs KD patients without shock (+1.36; P < 0.001) and MIS-C patients with shock (+1.45 [vs +1.32 for MIS-C patients without shock]; P < 0.001). They were also more likely to have large coronary artery aneurysms. In contrast, MIS-C patients with shock had lower left ventricular ejection fraction (mean 51.6%) vs MIS-C patients without shock (56.6%; P < 0.001) and KD patients with shock (56.7% [vs 62.8% for KD patients without shock]; P = 0.04).

Although patients with KD presenting with shock are clinically similar to patients with MIS-C, especially those with shock, they have more severe coronary artery involvement, whereas MIS-C patients with shock have lower left ventricular ejection fraction.

Dysregulated innate immune responses contribute to multisystem inflammatory syndrome in children (MIS-C), characterized by gastrointestinal, mucocutaneous, and/or cardiovascular injury occurring weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To investigate innate immune functions, we stimulated ex vivo peripheral blood cells from MIS-C patients with agonists of Toll-like receptors (TLR), key innate immune response initiators. We found severely dampened cytokine responses and elevated gene expression of negative regulators of TLR signaling. Increased plasma levels of zonulin, a gut leakage marker, were also detected. These effects were also observed in fully convalescent children months after MIS-C recovery. When we investigated the genetic background of patients in relation to TLR responsiveness, we found that cells from MIS-C children carrying rare heterozygous variants of lysosomal trafficking regulator (LYST) were less refractory to TLR stimulation and exhibited lysosomal and mitochondrial abnormalities with altered energy metabolism. Moreover, these rare LYST variant heterozygous carriers tended to exhibit unfavorable clinical laboratory indicators of inflammation, including more profound lymphopenia. The results of our observational study have several implications. First, TLR hyporesponsiveness may be associated with hyperinflammation and/or excessive or prolonged stimulation with gut-originated TLR ligands. Second, TLR hyporesponsiveness during MIS-C may be protective, since LYST variant heterozygous carriers exhibited reduced TLR hyporesponsiveness and unfavorable clinical laboratory indicators of inflammation. Thus, links may exist between genetic background, ability to establish a refractory immune state, and MIS-C clinical spectrum. Third, the possibility exists that prolonged TLR hyporesponsiveness is one of the mechanisms driving long coronavirus disease (COVID), which highlights the need to monitor long-term consequences of MIS-C.

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.

Numerous inflammatory complications related to COVID are described, including the Multisystem inflammatory Syndrome in Children (MIS-C) and Hyperinflammation. There is a scarcity of studies comparing these two groups.

Retrospective longitudinal outcome-conditioned study. Demographic, clinical, and laboratory variables are analyzed. Patients with history of COVID contact or infection with at least 24 h of fever, two or more systems involved and up to 21 years were included. Patients with no laboratory signal of inflammation or with other diagnoses for the condition were excluded. Demographic and laboratory data are presented as medians with interquartile ranges. Dichotomous variables and prevalences are reported as percentages. A ROC curve analysis was conducted to assess the discriminatory ability of these tests in relation to the MIS-C and hyperinflammation groups.

We present fifty-four patients, thirty-one with MIS-C and twenty-three with hyperinflammation. The most frequent symptom in the MIS-C group was altered mental status in 61% vs. 46% (p = 0.014) and conjunctival hyperemia in 29% vs. 4% (p = 0.032). The most frequent laboratory findings were hypoalbuminemia in 68% vs. 26% (p = 0.002), increased serum troponin in 42% vs. 26% (p = 0.034), increased d-dimers in 94% vs. 76% (p = 0.015), as well as increased BNP in 55% vs. 17% (p = 0.02). On the other hand, the hyperinflammation group more frequently presented respiratory dysfunction in 57% vs. 13% (p = < 0.001) and serum ferritin equal or greater than 500 ng/mL in 94% vs. 77% (p = 0.046).

This is an original study comparing clinical and laboratory findings between MIS-C and hyperinflammation due to COVID. Altered mental status is more frequently associated with MIS-C while respiratory symptoms are associated with hyperinflammation. In addition, regarding laboratory tests, there is hypoalbuminemia, increase in serum troponin, BNP, and D-dimers specially in the MIS-C group and hyperferritinemia in the hyperinflammation group. Further studies are needed to assess the cutoff point of biological markers such as BNP, troponin, and d-dimers for diagnosis and/or prognosis in the pediatric population with MIS-C.

Background: Kawasaki disease (KD) is an acute inflammatory vasculitis with a particularly high incidence of coronary artery complications and constitutes a significant cause of acquired heart disease in children and young adults. Methods: We conducted a retrospective analysis of consecutive patients aged 0-18 years hospitalized at the "Prof. Dr. Matei Balş" National Institute of Infectious Diseases in Bucharest with Kawasaki disease over a period of 6 years (2018-2023). Results: A total of 25 children were discharged from hospital with this diagnosis during the analyzed period. The mean age was 2.9 years, and 56% were boys. Fever ≥5 days was present in all cases, and the most frequent additional sign was the presence of oral changes. Patients were treated according to in-effect guidelines with intravenous immunoglobulin (IVIG) (100%) and acetylsalicylic acid (68%). Only two cases were considered IVIG resistant and received a second IVIG infusion. Only mild cardiovascular changes were noted in echocardiography: mild coronary artery dilatation (21.7% of cases), mild valvular regurgitation, and small pericardial effusion. Infants displayed less inflammation and higher percentages of leukocytosis, developed an increase in platelet count sooner, received IVIG faster, and had longer hospital stays. Outcomes were generally favorable, and 92% of children were discharged, while the two remaining patients were transferred to other centers. No deaths were recorded. Conclusions: To our knowledge, this is the largest contemporary Romanian cohort of Kawasaki disease published to date, outlining the local diagnostic process, therapeutic strategies, and early outcomes of Kawasaki disease.

As a first-line therapeutic option for multisystem inflammatory syndrome in children (MIS-C) with surging demand, intravenous immunoglobulin (IVIG) is associated with escalating costs and supply shortages, particularly in low-income and middle-income countries. This study compares the effectiveness of methylprednisolone alone versus IVIG combined with methylprednisolone for managing MIS-C.

We conducted a retrospective cohort study from January 2022 to June 2023 at Vietnam National Children's Hospital. We used propensity score matching to compare the short-term outcomes based on immunomodulatory therapy with methylprednisolone alone or IVIG plus methylprednisolone.

We included 391 patients, comprising 255 boys and 136 girls, who fulfilled the MIS-C case definition of the US Centers for Disease Control and Prevention. Most patients (80.8%) received intravenous methylprednisolone monotherapy, and 19.2% were administered IVIG in addition to methylprednisolone. In general, the laboratory values indicative of hyperinflammatory and hyperthrombotic states displayed significant early response within 2-3 days after initial treatment, including white cell count (SE=1.77, p<0.001), NEU (SE=0.76, p=0.03), C reactive protein (SE=-46.51, p<0.001), PLT (SE=38.05, p=0.002), fibrinogen (SE=-0.37, p=0.002), d-dimer (SE=-849.8, p=0.02)); while subsequent improvement in cardiac markers was also observed, with pro-B-type natriuretic peptide (SE=-165.2, p<0.001) on day 5 and troponin I (SE=-0.05, p=0.004) on day 7. After propensity score weighting, there were 41 patients in each treatment group. Notably, there were no significant differences in the incidence of cardiac events between treatment groups regarding left ventricular dysfunction and coronary artery dilation or aneurysms (10.3% vs 20.7%, p=0.074 and 63.4% vs 56.1%, p=0.653, respectively). While the median paediatric intensive care unit length of stay (LOS) and hospital LOS were slightly lengthier in the IVIG and methylprednisolone group compared with those of the methylprednisolone group, these differences were not statistically significant ((5 vs 4, p=0.782) and (9 vs 7, p=0.725), respectively).

Initial treatment with methylprednisolone monotherapy appears not inferior in effectiveness to adjunctive IVIG plus methylprednisolone in MIS-C. Further investigations in randomised controlled trials deserve to be undergone to clarify if IVIG-sparing glucocorticoids are a viable option for achieving favourable outcomes in MIS-C, particularly in resource-limited settings with barriers approaching IVIG therapy.

Rarely, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will lead to myocarditis associated with multisystem inflammatory syndrome in children (MIS-C). It remains unclear why MIS-C only targets specific children. To explore an association between coxsackievirus infections with MIS-C, we investigated the sero-epidemiology of CV in admitted pediatric patients in relation to the pandemic. This retrospective case-control study was performed by chart review of children (age ≤21 years) admitted to a tertiary care hospital with CV serological testing from January 2017 to August 2023. Clinical, laboratory, and imaging findings were used to classify patients as MIS-C and CV-unlikely or CV-possible for non-MIS-C patients. Out of 182 admissions (179 patients, median age, 6), CVB complement fixation (CF) assay on serotypes B1-B6 and CVA immunofluorescence assay IgG on serotypes A7, A9, A16, and A24 were positive in at least one serotype in 59.2% and 80.7% of cases, respectively. We observed a significant drop in CVB CF seropositivity during the peak of social distancing in 2020. The likelihood of elevated CVB CF titers was significantly higher in MIS-C than the CV-unlikely group (OR: 1.92, 95% CI: 1.02-3.63, P: 0.04) and showed a trend toward higher values in African Americans than Whites (OR: 1.57, 95% CI: 0.98-2.50, P: 0.057). The frequency of MIS-C was considerably higher in African Americans than Whites (18.1% versus 9%, P: 0.1). A higher likelihood of elevated CVB CF titers in patients with MIS-C compared with those unlikely to have acute CV infection along with a relatively higher frequency of MIS-C in African Americans warrants further investigation into the role of CVB infection in MIS-C development.IMPORTANCEThe emergence of multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic raised major concerns in providers caring for children. This condition presents a hyper-inflammation state that can lead to severe complications, including myocarditis and cardiogenic shock. The pathogenesis of MIS-C has not been fully understood. Understanding the pathogenesis of this condition is not only important for developing effective treatments but also for applying preventive strategies. A two-hit hypothesis leading to MIS-C has been proposed. Coxsackievirus infections are prevalent during childhood and can also cause myocarditis, and coxsackievirus B specifically has been shown to cause persistent RNA presence in host cells, leading to continued inflammation. Herein, we show that elevated coxsackievirus B titers are associated with MIS-C cases, implying a role of successive infections with these viruses contributing to such a hyperinflammatory state. This study supports the need for larger investigations into this association.

The psychological trauma following COVID-19 has been lengthy and fraught for some children and their families. The specific problems encountered by children rendered helpless and hopeless by watching others suffer, vicarious traumatisation, is explained in brief as it represents a central motif in clinical work in psychology. This paper will focus on what is known of the nature of psychological trauma in children and families with a focus on the individual clinical manifestations of personal significance. As a backdrop, consideration will be given to the epidemiological trends of psychological morbidity in and around the COVID-19 pandemic. Finally, the article seeks to provide readers with an appreciation of the dimensions of the neural legacy of COVID-19, a form of neurodisability developing in vulnerable children at a point in time, that is likely to emerge in children suffering an enduring trauma response.

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.

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.

Since the emergence of COVID-19 in December 2019, the novel SARS-CoV-2 virus has primarily affected adults, with children representing a smaller proportion of cases. However, the escalation of the pandemic has led to a notable increase in pediatric cases of Multisystem Inflammatory Syndrome in Children (MIS-C). The pathogenesis of MIS-C is largely attributed to immune-mediated mechanisms, such as cytokine storms and endothelial damage, following SARS-CoV-2 infection. In this review, we comprehensively describe MIS-C, including its definitions as proposed by the CDC, WHO, and RCPCH, which emphasize persistent fever, excessive inflammatory responses, and multi-organ involvement. Additionally, we summarize current treatment approaches, prioritizing immunotherapy with intravenous immunoglobulin and corticosteroids, along with anticoagulation therapy, and monoclonal antibodies in severe cases.

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.