Multisystem Inflammatory Syndrome Research Articles

Altered Spike Immunoglobulin G Fc N-Linked Glycans Are Associated With Hyperinflammatory State in Adult Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome in Children.

Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines. We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay. Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups. We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology.

A Study of Hydroelectrolytic and Acid-Base Disturbances in MIS-C Patients: A Perspective on Antidiuretic Hormone Secretion.

COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) is a rare autoimmune disorder characterized by a range of polymorphic manifestations, similar to but distinct from other well-known inflammatory syndromes in children. We conducted a retrospective-descriptive study in which we summarized the clinical presentation of, biomarker variations in, and complications occurring in patients diagnosed with MIS-C, admitted to the Emergency Clinical Hospital for Children "Sf. Ioan", Galati, between July 2020 and June 2024. A total of 36 children met the MIS-C classification criteria according to the WHO-approved case definitions. A total of 41.7% (n = 15) were male and 58.3% (n = 21) were female. The median age of the study group was 4 years (IQR: 1.75-9.25 years). Surgical involvement was suspected in 16.7% (n = 6) of the patients, while 52.8% (n = 19) required intensive care. Clinically, fever was the most common symptom present in 89% (n = 32) of the cases. Gastrointestinal disorders were also common, with 50% (n = 18) presenting with inappetence, 42% (n = 15) with vomiting, and 39% (n = 14) with abdominal pain from admission, which worsened over time. Paraclinically, all patients exhibited signs of inflammation, and 86.1% (n = 31) had hydroelectrolytic and acid-base imbalances. The median hospital stay was 10 days (IQR: 7-12 days), with a stagnant clinical course in most cases. The inflammatory mechanisms in MIS-C, which can affect the secretion of antidiuretic hormone (ADH), were correlated with hydroelectrolytic disturbances and may lead to severe complications. For this reason, it is imperative to evaluate hydroelectrolytic disorders in the context of MIS-C and use diagnostic and prognostic biomarkers to develop effective therapeutic management strategies, ultimately improving the quality of life of affected children.

NK Cell and Monocyte Dysfunction in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection characterized by multiorgan involvement and inflammation. Testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Despite strong Ab production in MIS-C, SARS-CoV-2 nucleic acid testing can remain positive for 4-6 wk postinfection. Therefore, we hypothesized that dysfunctional cell-mediated Ab responses downstream of Ab production may be responsible for delayed clearance of viral products in MIS-C. In MIS-C, monocytes were hyperfunctional for phagocytosis and cytokine production, whereas NK cells were hypofunctional for both killing and cytokine production. The decreased NK cell cytotoxicity correlated with an NK exhaustion marker signature and systemic IL-6 levels. Potentially providing a therapeutic option, cellular engagers of CD16 and SARS-CoV-2 proteins were found to rescue NK cell function invitro. Taken together, our results reveal dysregulation in Ab-mediated cellular responses of myeloid and NK cells that likely contribute to the immune pathology of this disease.

Antibody-mediated cellular responses are dysregulated in Multisystem Inflammatory Syndrome in Children (MIS-C)

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare and severe complication of SARS-CoV-2 infection that is characterized by multi-organ involvement and substantial inflammation. The immunological responses in MIS-C are not fully known. Antibody-mediated viral clearance in which innate immune cells interact with antibodies via their Fc receptors to remove the virus is an important mechanism for reducing SARS-CoV-2 viral load. However, little is known about how antibody-mediated cellular responses in MIS-C compared to acute COVID-19 infection and direct testing of cellular function ex vivo to understand the aberrant immune response in MIS-C is limited. Therefore, we focused on the antibody-mediated cellular responses in MIS-C relative to children and adults that had acute COVID-19 infection with spectrum of symptoms. We hypothesized that cells that bind antibodies to help clear the virus are dysfunctional in MIS-C patients, preventing the virus from being fully cleared. Methods We collected samples from MIS-C children along with pediatric and adult subjects with a clinical spectrum of COVID-19 symptoms and uninfected controls. Through these controls, we can compare Fc-mediated antibody functions between ages and clinical symptoms. We utilized high dimension flow cytometry to assess phenotype and function of innate immune cells that bind to antibodies and sequencing to study Fc receptor genetic. This data was then correlated with matched clinical data. Results Monocytes in MIS-C were hyperfunctional for antibody-dependent cellular phagocytosis and production of proinflammatory cytokines. In contrast, natural killer (NK) cells in MIS-C were hypofunctional for antibody-dependent cellular cytotoxicity and cytokine production. To provide some preliminary insight into mechanism, we show multiple ways leading to decreased cytotoxicity for NK cells, including phenotypic exhaustion of NK cells, variants in CD16 (NK cell Fc receptor) genetics that reduce Fc binding to IgG, and cytokine-induced associations. Using a novel anti-CD16 novel bispecific reagent that we developed, we could rescue the hypofunctional antibody-mediated NK cell function in MIS-C to the same levels as control. Conclusion Together, our results reveal dysregulation in antibody-mediated responses that are unique to MIS-C and may contribute to the immune pathology of this disease. Specifically, we find that monocytes are hyperfunctional with NK cells are hypofunctional. In the case of the MIS-C antibody-mediated response, while it is likely that multiple pathogenetic mechanisms contribute to MIS-C, our data suggest an imbalance of the antibody-mediated cellular response as a mechanistic correlate of this rare, but life-threatening outcome of SARS-COV-2 in children. Our results highlight that targeted therapies to reduce viral burden and/or boost NK cells responses while decreasing cytokine levels may be effective in preventing MIS-C.

Cardiovascular manifestations in pediatric multisystem inflammatory syndrome associated with COVID-19 in a tertiary care pediatric center in Mexico City

Cardiovascular manifestations in pediatric multisystem inflammatory syndrome associated with COVID-19 in a tertiary care pediatric center in Mexico City

Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19-PIMS-grade 3: A Case Report

Background: In the face of the rise of COVID-19, the multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 has been reported, and an increase in MIS-C cases has been observed throughout the world. The majority of these cases were similar to Kawasaki disease concerning clinical presentation. Case Presentation: Despite similarities, MIS-C cases present clinical and laboratory differentiation, which makes it essential to portray similar cases worldwide to have a better consensus in the future. A 7-year-old male child visited the hospital with the chief complaints of fever associated with chills, rigors, and excessive myalgia for 3 days. He had a history of elevated high C-reactive protein (CRP) of 42.7 mg/L. He was diagnosed with Paediatric inflammatory multisystem syndrome (PIMS)-grade 3. Here, for the first time, we bring an Indian MIS-C case with COVID-19-associated Paediatric inflammatory multisystem syndrome (PIMS)-grade 3. Conclusion: PIMS-TS infection in paediatrics is associated with a wider range of complications, and the importance of musculoskeletal complications in PIMS-TS has been discussed.

Clinical insights: Resolving the specter of cardiac sequelae in multisystem inflammatory syndrome in children (MIS-C) – A 24-month follow-up case series

Background: During the COVID-19 pandemic, multisystem inflammatory syndrome (MIS-C) emerged as a novel and severe complication. Objectives: The present prospective study followed patients in Brazil from February 2020 to December 2022, and evaluated children discharged from reference centers with an MIS-C diagnosis. The aim of the study is to describe long-term cardiac findings. Methods: Following a clinical and imaging procedure, children with MIS-C were followed up. Results: Thirty-six children during hospitalization coursed with fever; 61.1 % presented with gastrointestinal symptoms, 77.7 % with cardiocirculatory manifestations, and 28 % with respiratory issues. Shock was observed in 37 % of patients and the average hospital stay was 9 ± 5 days, with 54 % exhibiting severe symptoms requiring intensive care. Elevated inflammatory and cardiac markers were common; 42 % of patients presented elevated troponin and D-dimer levels. During intensive care, echocardiographic abnormalities were found in 56 % of the patients, including coronary dilation and pericardial effusion. All patients were hospitalized and treated with intravenous immunoglobulin, oral steroids, and acetylsalicylic acid, resulting in 86 % recovery. However, 14 % of the patient had persistent (mild cardiac) alterations at discharge. Sex and previous chronic conditions did not affect the persistence of cardiac findings, whereas marginal age differences indicated that older children tend to have more severe symptoms. BMI was identified as a risk factor but must be considered carefully. Six months post-discharge, all patients successfully recovered from cardiac alterations. Conclusion: Only few case series have reported persistent MIS-C findings, and this case series elicits a positive post-discharge prognosis for MIS-C over time.

Delirium Associated with COVID-19 in Critically ill Children: An Observational Cohort Study.

Delirium is an under-recognized problem in critically ill children. Although delirium is common in adults hospitalized with COVID-19, the relationship between pediatric COVID-19 and delirium has not been described. To address this gap, we characterized delirium in critically ill children with different manifestations of COVID-19 and investigated associations among demographic, disease, and treatment factors. We hypothesized that multisystem inflammatory syndrome in children (MIS-C) would be associated with a higher incidence of delirium given its underlying pathophysiology of hyperinflammation. Retrospective, single-center cohort study. Quaternary-care pediatric intensive care unit (PICU). Children less than 18 years of age hospitalized in the PICU between March 2020 and March 2023 with either active SARS-CoV-2 infection or serological evidence of prior infection. The cohort included 149 PICU hospitalizations among children with evidence of COVID-19. Patients were categorized by reason for PICU admission: 75 (50%) for COVID-19 respiratory disease, 36 (24%) MIS-C, and 38 (26%) any other primary reason with positive COVID-19 testing. Delirium was diagnosed in 43 (29%) patients. Delirium incidence was highest in patients requiring invasive mechanical ventilation (IMV) (56% vs 7.5% in patients who did not require IMV, p < .001). Patients who were exposed to opioids, dexmedetomidine, paralytics or benzodiazepines more frequently experienced delirium compared to those unexposed (p < .001, p < .001, p < .001 and p = .001, respectively). After multivariable adjustment, delirium was associated with IMV (HR 3 [95% CI 1.5-5.7]), female sex (HR 2.4 [1.2-4.7]), and developmental disability (HR 3.4 [95% CI 1-11.1]). There was no association between delirium and reason for PICU hospitalization. Delirium was common among children hospitalized with COVID-19. The overall incidence was much less than has been reported in adults with COVID-19. Delirium reduction efforts should focus on children with developmental disability and minimizing ongoing risks during IMV.

Cytokine landscape in hospitalized children with multisystem inflammatory syndrome

The etiology of multisystem inflammatory syndrome in children (MIS-C), frequently observed following COVID-19 infection, remains elusive. This study unveils insights derived from cytokine analysis in the sera of MIS-C patients, both before and after the administration of intravenous immunoglobulin (IVIG) and glucocorticosteroids (GCS). In this study, we employed a comprehensive 45-cytokine profile encompassing a spectrum of widely recognized proinflammatory and antiinflammatory cytokines, as well as growth factors, along with other soluble mediators. The analysis delineates three principal cytokine-concentration patterns evident in the patients’ sera. Pattern no.1 predominantly features proinflammatory cytokines (IL-6, IL-15, IL-1ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), C-X-C motif chemokine ligand 10 (CXCL10/ IP-10), and IL-10) exhibiting elevated concentrations upon admission, swiftly normalizing post-hospital treatment. Pattern no. 2 includes cytokines (IL-17 A, IL-33, IFNγ, vascular endothelial growth factor (VEGF), and programmed death ligand (PD-L1)) with moderately elevated levels at admission, persisting over 7–10 days of hospitalization despite the treatment. Pattern no. 3 comprises cytokines which concentrations escalated after 7–10 days of hospitalization and therapy, including IL-1α, IL-1β, IL-2, IL-13, platelet-derived growth factor AA/BB (PDGF AA/BB). The observed in cytokine profile of MIS-C patients showed a transition from acute inflammation to sustaining inflammation which turned into induction of humoral memory mechanisms and various defense mechanisms, contributing to recovery.

AKI in Patients with Multisystem Inflammatory Syndrome in Children

AKI in Patients with Multisystem Inflammatory Syndrome in Children

Skin manifestations and related clinical characteristics of multisystem inflammatory syndrome in children: A descriptive retrospective cohort study at Texas Children’s Hospital

BackgroundLittle is known about the dermatologic manifestations of MIS-C in children and adolescents ObjectiveWe 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. MethodsDescriptive retrospective cohort study of 290 hospitalized eligible patients between May 2020 and April 2022. ResultsAmong MIS-C patients, 51% exhibited a rash. We found that younger children (8.62 vs. 9.49 years of age, p=0.006) and white children (p=0.002) 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=0.02) and a higher incidence of cardiac involvement (83.1% vs. 72.3%, p=0.03) 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. LimitationsRash characteristics were initially described by a variety of physicians on the pediatric primary care services. ConclusionRash manifestations in MIS-C patients is associated with lower Cardiac involvement and decreased troponin levels.

Surgical aspects of pediatric abdominal pain in the era of COVID-19: clinical consideration and outcomes.

Acute abdominal pain in pediatrics is a medical emergency that requires special attention. During COVID-19 pandemic, this disease presented in pediatric age by different presentations including abdominal presentations.The affected children are presented with abdominal pain, which may be caused by surgical causes or by the virus itself that necessitate surgical consultation. This study highlights the impact of the coronavirus pandemic on pediatric patients with acute abdominal pain regarding the presentation, clinical evaluation, and surgical management. A retrospective cohort study was done through the collection of data from medical records and authors' data repositories of pediatric patients presented with acute abdomen from March 2020 to March 2022, in three pediatric surgery tertiary centers. Eighty-four pediatric patients with acute abdominal pain were included in this study. The diagnosis of acute appendicitis was found in 31 patients (36.9%). Generalized abdominal pain was noted in 17 patients (20.2%) and presentation mimicked acute cholecystitis was occured in 14 patients (16.7%). ultrasonography revealed intussusception in 12 cases (14.3%). Multisystem inflammatory syndrome in children (MIS-C) was present in 9 cases (10.7%) and only one case of pancreatitis (1.2%). Conservative management was successful in 66 cases (78.6%), while operative intervention was needed in18 cases (21.4%). During the COVID-19 pandemic, acute abdominal pain in children was frequently observed. Careful follow up is critically important as most cases do not necessitate surgical intervention. It is crucial to consider COVID-19 as a differential diagnosis in children presenting with acute abdominal pain, particularly in cases of atypical appendicitis and intussusception to prevent unnecessary surgical procedures.

A Comparison of Kawasaki Disease during the SARS-CoV-2 Pandemic with Multisystem Inflammatory Syndrome in Children.

The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD.

Clinical characteristics and outcomes of neonatal SARS-CoV-2 infection after the release of the epidemic situation of COVID-19

BackgroundWith the release of the coronavirus disease 2019 (COVID-19) pandemic in late 2022 in China, the number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) roared, including neonatal cases. However, there were few studies on neonatal COVID-19, especially multi-center case reports. This study aimed to explore clinical characteristics and short-term outcomes of neonatal COVID-19 in China.MethodsWe reviewed 187 cases of neonatal COVID-19 between December 11, 2022, and January 12, 2023. The diagnosis was assessed by symptoms, laboratory tests, X-ray manifestations, and diagnosis code. Clinical characteristics and outcomes were evaluated.ResultsIn 187 neonatal cases with COVID-19, 84 (44.9%) had severe SARS-CoV-2 infection. Most patients had confirmed exposure to SARS-CoV-2. Fever and respiratory symptoms were common (75.4% and 71.7%, respectively). Severe patients were more likely to have high alanine transaminase (ALT) (> 40U/L) (11.9% vs. 3.9%) and high N-terminal pro-brain natriuretic peptide (NT-proBNP) (> 2000pg/mL) (38.0% vs. 19.6%), compared with nonsevere ones (P < 0.05). None of the patients received COVID-19-specific medical interventions. A few severe patients received corticosteroids (1.1%), and immunoglobulin (0.5%), respectively. All patients were discharged home after the medical care with a median length of stay (LOS) of four days and none of them met the criteria of multisystem inflammatory syndrome in neonates (MIS-N).ConclusionsAfter the release of the epidemic situation of COVID-19 in late 2022 in China, more neonatal cases with severe COVID-19 had high ALT and NT-proBNP level. Few specific medical interventions were given, and the outcome was satisfying.

Rare genetic variants of NLRP12 in Admixed Latino-American Children with SARS-CoV-2-related Multisystem Inflammatory Syndrome.

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 NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-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.

Asymptomatic SARS-COV2 Infection or COVID-19 vaccination effect for severe multisystem inflammatory syndrome in a 6-year-old girl: case report and review of the literature

BackgroundMultisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3–6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5–11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection.Case presentationWe describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae.ConclusionsThis case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old.

Clinical Effectiveness of Biological Immunomodulators in SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children: A Systematic Review.

Although there is consensus to use immunoglobulins and corticosteroids as first-line treatments for multisystem inflammatory syndrome in children (MIS-C), the effectiveness of biological immunomodulators in patients refractory to standard therapy remains unclear. We aimed to outline real-world data on biological immunomodulators. A literature search using Ovid-Medline, EMBASE, Cochrane CDSR, and KMBASE was conducted from September 2021 to August 2022; certainty of evidence was assessed via GRADE. Among 258 studies, 10 were selected for analysis, of which 2 were observational studies (with control groups receiving standard therapy of either intravenous immunoglobulins and/or glucocorticoids) and 8 were single-arm studies. In all, 145 patients were treated with biological immunomodulators (anakinra (72; 49%) or infliximab (65; 44%)). In the first observational study, patients in the anakinra group initially exhibited a lower left ventricular ejection fraction than those in the control group. In the second study, patients in the infliximab group required less additional therapy and showed lower newly developed left ventricular dysfunction rate and reduced C-reactive protein levels. The clinical outcomes associated with each biological agent in single-arm studies were not reported individually. Biological immunomodulators are feasible therapeutic options for refractory MIS-C. Nevertheless, further research is warranted to demonstrate clinical efficacy.

Proteomic Signatures of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19: A Narrative Review.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of COVID-19. MIS-C has overlapping features with other pediatric inflammatory disorders including Kawasaki Disease (KD), Macrophage Activation Syndrome (MAS), Toxic Shock Syndrome and sepsis. The exact mechanisms responsible for the clinical overlap between MIS-C and these conditions remain unclear, and biomarkers that could distinguish MIS-C from its clinical mimics are lacking. This study aimed to provide an overview of how proteomic methods, like Mass Spectrometry (MS) and affinity-based proteomics, can offer a detailed understanding of pathophysiology and aid in the diagnosis and prognosis of MIS-C. A narrative review of relevant studies published up to July 2024 was conducted. We identified 15 studies and summarized their key proteomic findings. These studies investigated the serum or plasma proteome of MIS-C patients using MS, Proximity Extension, or Aptamer-based assays. The studies associated the proteomic profile of MIS-C with laboratory and clinical parameters and/or compared it with that of other diseases including acute COVID-19, KD, MAS, pediatric rheumatic diseases, sepsis and myocarditis or pericarditis following COVID-19 mRNA immunization. Depending on the method and the control group, different proteins were increased or decreased in the MIS-C group. The limitations and challenges in MIS-C proteomic research are also discussed, and future research recommendations are provided. Although proteomics appear to be a promising approach for understanding the pathogenesis and uncovering candidate biomarkers in MIS-C, proteomic studies are still needed to recognize and validate biomarkers that could accurately discriminate MIS-C from its clinical mimics.

Twenty-four Month Multidisciplinary Follow-up of Multisystemic Inflammatory Syndrome Patients in a Tertiary Pediatric Hospital in Chile: A Prospective Study.

Multisystemic inflammatory syndrome (MIS-C) is a severe postinfectious condition. This study aims to detail long-term follow-up. Forty-five patients were followed up for 24 months, inflammatory markers were normalized at 3 months and echocardiographic alterations were resolved in all patients at 6 months, remaining normal. MIS-C, despite being a serious disease, presents a fast resolution of clinical, laboratory and echocardiographic alterations.

Clinical and Laboratory Parameters Associated with PICU Admission in Children with Multisystem Inflammatory Syndrome Associated with COVID-19 (MIS-C).

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19 that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical, and laboratory characteristics of children diagnosed with MIS-C who were admitted to the PICU and those who did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Demographic, clinical, and laboratory data were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR: 12.89, 95%CI: 1.35-123.41, p-value = 0.03) and cardiological involvement (OR: 34.55, 95%CI: 2.2-541.91, p-value = 0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 h from admission, D-dimer levels higher than 4 μg/mL and decreased Left Ventricular Ejection Fraction (LVEF) were associated with an increased risk of PICU admission (OR: 7.95, 95%CI: 1.48-42.78, p-value = 0.02 and OR = 1.28, 95%CI: 1.07-1.53, p-value = 0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value = 0.005) and were hospitalized for more days than children in the pediatric ward (median length of stay (IQR): 20 (15, 28) days vs. 8.5 (6, 14) days, p-value < 0.001). Conclusions: The findings of this study indicate that cardiovascular and hepatic involvement and increased D-dimer levels in children with MIS-C might be associated with admission to the PICU.