Multisystem Inflammatory Syndrome In Children Research Articles

Multisystem inflammatory syndrome in children: an Umbrella review.

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

Imaging Evaluation of Clinical and Subclinical Myocarditis in Multisystem Inflammatory Syndrome of Children with COVID-19 Using Cardiac Magnetic Resonance: The Results and Prognosis

Background: Coronavirus disease 2019 (COVID-19) has emerged as the most significant health crisis in recent years, leading to over 6 million deaths globally due to the disease. Objectives: Given the prevalence of multisystem inflammatory syndrome in children (MISC) following the COVID-19 pandemic, this study aims to examine the imaging findings and prognoses of clinical and subclinical myocarditis in children with MISC through cardiac magnetic resonance (CMR) imaging. Patients and Methods: This prospective cohort study carried out over eighteen months from May 2021 to November 2022, included 14 patients who underwent CMR imaging. A census of all eligible patients during the study period served as the sampling method. Inclusion criteria were patients with confirmed COVID-19 infection through serological tests, polymerase chain reaction (PCR), or recent exposure to COVID-19 patients. Exclusion criteria included patients with a history of congenital heart disease (CHD) or pulmonary disease. Additional diagnostic tests performed included blood sample tests, chest X-ray (CXR), electrocardiogram (ECG), and echocardiography. CMR imaging was conducted on patients with cardiac involvement. A diagnosis of myocardial inflammation was made if a patient met at least two of the Lake Louise Criteria. The Chi-square, Fisher's exact, and Mann-Whitney tests were used to examine the relationship between quantitative variables and treatment outcomes. Additionally, the Wilcoxon signed rank, and McNemar’s tests assessed changes in echocardiography findings from admission to follow-up. A significance level of 0.05 was set. Results: Among the 14 patients studied, 8 (57.10%) were girls and 6 (42.90%) were boys. The average age was 6.03 ± 3.71 years. The median time to CMR imaging after symptom onset was 4 weeks (interquartile range (IQR): 2 - 12, range: 30). Global function assessment using left ventricular ejection fraction (LVEF) showed that 5 (35.70%), 3 (21.40%), and 6 (42.90%) patients had normal function, mild dysfunction, and significant LV dysfunction, respectively. 71.40% of patients who recovered had mild tricuspid regurgitation (TR) and no cardiomegaly. Significant differences in mean values of polymorphonuclear neutrophil (PMN) (37.71 ± 11.75 vs. 81.44 ± 13.06), lymphocytes (48.71 ± 20.08 vs. 12.51 ± 7.26), hemoglobin (Hb) (12.60 ± 1.55 vs. 10.10 ± 1.62), mean corpuscular volume (MCV) (85.90 ± 5.67 vs. 79.37 ± 5.23), erythrocyte sedimentation rate (ESR) (8.86 ± 13.60 vs. 30.29 ± 21.33), and C-reactive protein (CRP) (18.91 ± 27.25 vs. 100.57 ± 85.67) were observed between non-recovered and recovered patients, respectively (P < 0.05). However, no statistically significant association was found between other variables, including N-terminal pro–B-type natriuretic peptide (NT-proBNP), D-dimer, and Troponin I (TPI), with treatment outcomes (P > 0.05). Conclusion: Our findings indicate that a negative COVID-19 test does not exclude an established clinical COVID-19 infection in children with MISC. The results suggest that all children with MISC and a history of COVID-19 infection should undergo assessment for myocardial fibrosis, regardless of ejection fraction (EF) as determined by Echocardiography, laboratory tests, and COVID-19 test results. Strain analysis, conducted during both the acute phase and subsequent follow-ups through CMR imaging or Echocardiography, is recommended to enhance the understanding of the prognosis.

Should we be afraid of long-term cardiac consequences in children with multisystem inflammatory syndrome? Experience from subsequent waves of COVID-19.

The purpose of the study was to assess and compare short- and long-term cardiac complications of the multisystem inflammatory syndrome in children (MIS-C) by predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants throughout the pandemic. The analysis of prospectively collected data comparing cardiac complications of MIS-C during and after hospitalization across the original/alpha, delta, and omicron waves. Cardiac complications were defined as cardiac failure with systolic function impairment or hypotension or abnormalities in echocardiographic findings (decrease in LVEF, FS, valvular insufficiency, pericardial effusion, or coronary artery abnormalities). A total of 120 patients with MIS-C admitted to the Children's Hospital of Krakow between November 1, 2020, and May 5, 2023, were included in the study (74 during original/alpha dominance, 31 delta, and 15 omicron). Patients in the omicron group were found to be younger than those in the alpha and delta groups (37 vs. 75 vs. 80months, p = 0.03). The frequency of cardiac failure with systolic function impairment or hypotension was diagnosed more frequently in the original/alpha and delta groups than in the omicron group (44.59% vs. 41.94% vs. 13.33%, p = 0.08) also echocardiographic abnormalities changed, with rates of 60.8%, 35.5%, and 13.3% (p < 0.001) accordingly. The multivariable regression revealed an older age (OR = 1.19, 95% CI = 1.07-1.33, p = 0.002) as the only independent factors of cardiac failure with systolic function impairment or hypotension. In all patients, signs of cardiac failure resolved during the hospitalization. Moreover, in 98.3% of patients, all echocardiagraphic abnormalities resolved completely during the observation period. Conclusion: The cardiac complications of MIS-C appeared to advance less severely in younger children during the Omicron outbreak. In long-term observation, symptoms of cardiac failure resolve completely. Similarly, also echocardiographic abnormalities normalize in the vast majority of patients. What is Known: • Knowledge about the long-term cardiac complications of MIS-C is still evolving and uncertain. • The greatest concern of MIS-C is cardiac complications, including cardiac failure and coronary artery dilatation. What is New: • Long-term observations revealed complete resolution of cardiac complications in the vast majority of patients with MIS-C, irrespective of the dominant variant. • Cardiac complications of MIS-C were less common in younger children during subsequent pandemic waves in our patient population.

Treatment of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically. We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms "multisystem inflammatory syndrome", "MIS-C", "PIMS-TS", "therapy", "treatment", "drug", "IVIG", "GCs", "intravenous immunoglobulin", "corticosteroids", "biological agent", and "aspirin". The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C. MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols. Supplementary file1 (MP4 208044 kb).

Frosted Branch Angiitis Associated with COVID-19-related Multisystem Inflammatory Syndrome in Children

Purpose: To report a case of frosted branch angiitis associated with COVID-19-related multisystem inflammatory syndrome in children (MIS-C).Case summary: An 8-year-old boy was referred to the ophthalmology clinic with decreased visual acuity in his right eye. The initial best-corrected visual acuity (BCVA) was 20/63 in the right eye and 20/32 in the left eye. Upon fundus examination, bilateral frosted branch-like vascular sheathing and retinal hemorrhage were observed. Optical coherence tomography (OCT) demonstrated macular edema. Fluorescein angiography revealed late staining and leakage of affected retinal vessels. The patient exhibited persistent fever, rash, and gastrointestinal symptoms, accompanied by an increase in inflammatory markers in laboratory tests. Testing for SARS-CoV-2 immunoglobulin G (IgG) was positive, although there was no evidence of any other autoimmune diseases or viral infections. The patient was diagnosed with frosted branch angiitis associated with MIS-C. Treatment included systemic steroids and 1% prednisolone eye drops. After 2 weeks, the BCVA improved to 20/20 in both eyes, and all clinical signs resolved without recurrence.Conclusions: In patients with frosted branch angiitis without any other apparent cause, the possibility of MIS-C should be considered. Testing for COVID-19 infection is recommended.

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

Clinical presentation and management of multisystem inflammatory syndrome in children associated with covid-19: a retrospective observational descriptive study in a pediatric hospital in Syria

ObjectiveMultisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a rare and serious medical condition. This study aims to review the clinical presentation, laboratory parameters, outcomes, and management of MIS-C cases in a pediatric hospital in Syria.MethodsThis retrospective observational study aimed to investigate MIS-C between May 2020 and October 2021. Data collection involved extracting information from medical records, and patients were identified based on the case definition established by the World Health Organization (WHO). Various laboratory investigations, diagnostic evaluations, clinical presentations, and treatments were performed to assess patients. Descriptive statistical analysis was conducted using Microsoft Excel.ResultsA total of 232 COVID-19 cases were reported with COVID-19 Infection. Among these cases, 25 (10.77%) were identified as MIS-C. The median age of the patients was 5.5 years, with the majority being male patients (72%). Patients experienced fever (100%), bilateral conjunctivitis (88%), rash (84%), gastrointestinal symptoms (76%), and cardiac dysfunction (72%). Other notable findings included oral cavity changes (64%), edema (36%), cervical lymphadenopathy (36%), and neurological manifestations (28%). Respiratory symptoms were uncommon (16%). All patients recovered, with no recorded deaths.ConclusionThe predominant presence of positive SARS-CoV-2 IgG in the majority of patients in this study supports the post-infectious nature of MIS-C. Respiratory symptoms were less prevalent in both pediatric COVID-19 and MIS-C patients. Early supportive care is crucial in management, although additional research is needed to establish definitive guidelines. Larger studies are necessary to overcome the limitations of this study and to enhance our understanding of MIS-C in pediatric COVID-19 patients.

Multisystem inflammatory syndrome in children (MIS-C) post-COVID-19 in Iran: clinical profile, cardiac features, and outcomes

BackgroundIn April 2020, an association between multisystem inflammatory syndromes (MIS-C) was observed in children with severe acute respiratory syndrome coronavirus infection (SARS-CoV-2). Most patients had heart involvement alone, and most patients had pericardial effusion. This study aimed to express and emphasize cardiac involvement in pediatric patients with respiratory symptoms who were diagnosed with COVID-19.MethodsThis study was conducted in July 2021 in Kerman province, Southeastern Iran, during a notable surge in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The study included 904 pediatric patients diagnosed with COVID-19. Data collection involved a comprehensive assessment of clinical symptoms and manifestations. Patients with fever lasting more than five days were admitted to the hospital. Echocardiography was utilized for cardiac involvement diagnosis, with 47 patients undergoing this diagnostic procedure.ResultsOf the 904 patients, most of them had high fevers (74%). Fifty-five patients had a fever for more than five days and were hospitalized. Of the 47 patients who underwent echocardiography, 45 (81%) had heart involvement. In 75% of patients, pericardial effusion was the only cardiac involvement. Patients with pericardial effusion were treated with dexamethasone up to 3 mg every 8 h for 72 h.ConclusionsMIS-C has a wide range of clinical symptoms. In cases where the fever is prolonged and there are gastrointestinal symptoms, physicians have clinical suspicion to diagnose this syndrome. Most cases of pericardial effusion are alone and improve with treatment with glucocorticosteroids.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n=259) or multisystem inflammatory syndrome in children (MIS-C; n=4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

The Clinical and Molecular Findings of Patients with Multisystem Inflammatory Syndrome in Children (MIS-C)

Background: several children with COVID-19 disease present with fever, gastrointestinal symptoms, rash, conjunctivitis, mucosal changes, shock, and myocardial dysfunction, called multisystem inflammatory syndrome in children (MIS-C), similar to incomplete Kawasaki disease or toxic shock syndrome. The unclear pathophysiology of MIS-C prompts clinical and genetic evaluation of the patients.&#x0D; Method: In the present study, patients with MIS-C disease who were referred by medical specialists of Imam Ali Hospital of Alborz in 2020-2021 were included. The clinical manifestations and laboratory findings of enrolled patients were evaluated, and the genetic analysis was performed by whole exome sequencing (WES), further confirmed by Sanger sequencing.&#x0D; Results: Among 11 patients diagnosed with MISC, six patients (54.5%) were male, and the mean (SD) age of participants was 6.55 (±2.81) years. The most prevalent clinical presentations included fever (100%), rash (82%), bilateral non-purulent conjunctivitis (73%), and mucous membrane changes (64%). The only patient with genetic alterations was an 8-year-old boy with a homozygous missense variant of the ATP6AP1 gene and a heterozygous likely pathogenic canonical splice site variant of the M1B1 gene.&#x0D; Conclusion: Although the young age of patients with MIS-C and their autoinflammatory presentations are similar to patients with inborn errors of immunity, the results indicate that most patients with MIS-C do not have genetic mutations.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

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

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

Echocardiographic Strain Evaluation Shows Persistent Echocardiographic Changes at 1 Year after Diagnosis of Multisystem Inflammatory Syndrome in Children.

Coronavirus disease (COVID-19) is a global pandemic causing multisystem inflammatory syndrome in children (MIS-C). This study evaluated the long-term echocardiographic impact of MIS-C on patients and compared it with that in a healthy control group. Data from 22 children with MIS-C admitted to Jeonbuk National University Hospital and 22 healthy children (control group) were retrospectively analyzed. Echocardiographic data were compared at two distinct time points: diagnosis and 1-year follow-up. At diagnosis, the MIS-C cohort exhibited significantly reduced left ventricular ejection fraction (LVEF), longitudinal strain across the apical 4- and 2-chamber views, and global longitudinal strain (GLS). At 1-year follow-up, the reduced LVEF in the apical 4-chamber, overall longitudinal strain in the apical 4-chamber, and GLS persisted. However, the right ventricular free wall and global strain remained diminished compared with those in the control group. Despite significant changes over time, the LVEF and longitudinal strain in the apical 4-chamber and z-scores of all coronary arteries were normal at baseline and 1-year follow-up. Persistent cardiac alterations were observed in patients with MIS-C, particularly in both ventricular functions. Therefore, middle- to long-term echocardiographic follow-up may help improve understanding and management of long-term echocardiographic implications in patients with post-COVID-19 syndrome.

Electrocardiography in Children Hospitalized for COVID-19 and Not Suffering from Multisystem Inflammatory Syndrome in Children (MIS-C): An Observational Study.

The risk of cardiac involvement with electrophysiological abnormalities during COVID-19 infection has been reported in adults but remains poorly studied in children. Our aim was to determine the frequency of cardiac involvement and the necessity of routine cardiac evaluation in children hospitalized for COVID-19. This observational study included 127 children, with a median (IQR) age of 2 (0.83-6.0) years, who were hospitalized for COVID-19 between 1 January 2021 and 31 August 2022, 62 (48.8%) of whom were males. Each patient underwent an ECG on admission and discharge as well as a laboratory assessment. A comparison between patients with COVID-19 and healthy controls showed significantly higher HR (p < 0.0001) and lower PR values (p = 0.02) in the first group. No arrhythmias or other electrocardiographic abnormalities were detected during hospitalization. The median levels of troponin, NT-proBNP, ferritin, and D-dimer were significantly higher in children aged <2 years, but they fell within the normal range for their age. Our results indicate that a detectable cardiac involvement is very rare in children hospitalized for COVID-19 and not suffering from Multisystem Inflammatory Syndrome in Children (MIS-C) and suggest that routine electrocardiographic assessment is not mandatory in these patients in the absence of cardiac symptoms/signs.

Cardiac Function in Pediatric Patients with MIS-C Using Speckle Tracking and Conventional Echocardiography: A Longitudinal, Single-Center Study.

Cardiovascular involvement in Multisystem Inflammatory Syndrome in Children (MIS-C), a potential consequence of coronavirus disease-2019 (COVID-19), is common. Conventional transthoracic echocardiography (TTE) provides primary data on the function of the left and right ventricles, while Speckle Tracking Echocardiography (STE) is more sensitive. This study aims to assess longitudinal cardiac function using STE in these patients. This longitudinal study was conducted from late 2021 to early 2022 at Imam Hossein Children's Hospital, Isfahan. Cardiac function was assessed by STE at the time of diagnosis and again two months later. Demographics, clinical characteristics, ECG interpretations, imaging studies, and serum cardiac marker levels were collected. Thirty-five pediatric patients with a mean age of 5.1 years (range: 4 months to 17 years) were included and prospectively followed. Twenty-nine of them, comprising 14 males (48.3%) and 15 females (51.7%), underwent STE and were compared with 29 healthy age- and sex-matched children. Factors related to adverse events included reduced myocardial function, enlarged left atrium or ventricle, and mitral regurgitation (MR). Patients with comorbidities affecting strain measurements were excluded from the strain analyses. A significant difference was observed between the groups in regional strains in the basal and apical septal and middle lateral regions. Global strain rate (GLS) and strain rates were not significantly different but were still lower than the control group. Twenty percent of patients had abnormal GLS but normal left ventricular ejection fraction (LVEF). All patients exhibited reduced segmental myocardial strain in at least one segment. Four out of 26 recovered patients without comorbidities had abnormal GLS at follow-up, despite normal LVEF. STE proves more useful than conventional echocardiography in patients with MIS-C, revealing subclinical cardiac injury in the acute and post-acute phases.

Differentiating Multisystem Inflammatory Syndrome in Children from Kawasaki Disease During the Pandemic.

We aimed to delineate the distinctive characteristics that aid in distinguishing between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with KD-like manifestations during the pandemic. We evaluated KD patients and MIS-C patients with KD-like symptoms admitted during the pandemic (between January 2021 and December 2022). Thirty-three MIS-C patients and 15 KD patients were included. Kawasaki disease patients were younger than MIS-C patients (3.4 vs. 7.6 years). Rash (P = .044, 100% vs. 75.7%), oral mucosal changes (P = .044, 100% vs. 75.7%), and cervical lymphadenopathy (P = .001, 93.3% vs. 42.4%) were more common in KD. Multisystem inflammatory syndrome in children: patients had more hypotension (P = .002, 45.4% vs. 0), gastrointestinal (P .001, 72.7% vs. 13.3%), and respiratory symptoms (P = .044, 24.2% vs. 0). Multisystem inflammatory syndrome in children patients also had low lymphocyte and thrombocyte counts and elevated levels of d-dimer, ferritin, and cardiac parameters, unlike KD patients. Multisystem inflammatory syndrome in children patients exhibited a notable reduction in left ventricular systolic function in echocardiography. Another significant difference with regard to management was the anakinra treatment, which was prescribed for MIS-C patients. Although MIS-C patients might display a clinical resemblance to KD, several features could help differentiate between MIS-C and classical KD. Specific clinical (hypotension, gastrointestinal, and respiratory symptoms) and laboratory (low lymphocyte and thrombocyte counts with higher C-reactive protein, ferritin, d-dimer, and cardiac parameters) features are characteristic of MIS-C. In addition, divergence in management strategies is evident between the 2 diseases, as biologic drugs were more prevalently employed in MIS-C patients than in classical KD patients.

The evaluation of the burden of multisystem inflammatory syndrome in children on health economics.

This study aimed to evaluate the diagnostic tests and treatments applied in patients with multisystem inflammatory syndrome in children (MIS-C) and to determine the effect of the disease on health costs. This retrospective cohort study included 59 MIS-C patients (40 males, 19 females; mean age: 7.7±4.2 years; range, 4 months to 16.5 years) who were admitted and treated between April 1, 2020, and November 1, 2021. Demographic and clinical features with hospital costs and length of stay were retrospectively reviewed from the medical files and computerized system of the hospital. Direct medical care costs of items were calculated with the hospital perspective using a combination of microcosting technique (resource-based accounting method) and hospital list data. Cases were classified as mild, moderate, or severe, and the patients were divided into two groups: the mild group and the moderate-severe group. Classification was determined by the vasoactive inotropic score (VIS), degree of respiratory support, and evidence of organ damage. The mean age of the cases in the mild group was 6.5±3.7 years, and the mean age of the cases in the moderate-severe group was 9.2±4.3 years. Of 59 patients, 19 (32.2%) were followed up in the pediatric intensive care unit. The median duration of hospitalization in the hospital was 8 (interquartile range: 7-12) days. The total cost of the patients hospitalized with the diagnosis of MIS-C during the study period was 849,242.93$, and the mean cost per patient was 14,393.94±9,631.92$. In the distribution of the total cost of hospitalization according to expenses, the highest rate was pharmacy and blood products (51.99%) and IVIG costs (43.99%). While the mean total cost per person was 13,682.87±8,799.63$ in mild cases, it was 16,433.82±9,440.02$ in moderate-severe cases, and no statistically significant relationship was found between the two groups (p>0.05). There was no difference in the mean cost per patient between the cases with and without heart, lung, kidney, or neurologic involvement and advanced respiratory support (p>0.05). There was a strong positive correlation between the total costs and age (r=0.883, n=59, p<0.0001), with increased amount of costs with increased age. In the study, no statistically significant correlation was found between the total cost of per person in the mild group and the moderate-severe group (p>0.05). This finding may be due to the wide use of IVIG in MIS-C treatment, in addition to low transfer rates to pediatric intensive care units due to high-flow nasal cannula usage.

Ingresos COVID-19: intentando comprender el impacto real de la infección en pacientes hospitalizados

Introduction and objectiveSeveral studies have suggested that the hospitalization rate for COVID-19 in children and adolescents may reflect the prevalence of the infection rather than the severity of the disease. The aim of this study was to describe the clinical features of hospitalised paediatric patients with SARS-CoV-2 infection in order to understand if the infection was the reason for admission. MethodsRetrospective cohort study including patients aged 0 to 18 years with SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) admitted to a tertiary care children's hospital in Spain between 01/01/2020 and 12/31/2021. Results228 patients were included, corresponding to 150 cases of COVID-related admission (SARS-CoV-2 infection as main cause of hospitalization) and 78 of non-COVID-related admission (SARS-CoV-2 infection unrelated to the hospitalization).In the group of COVID-related admissions, 58 patients had comorbidities. Forty-nine patients had acute respiratory disease (pneumonia, bronchospasm or bronchiolitis). Multisystem inflammatory syndrome in children was diagnosed in 27 and was significantly more frequent in the first year of the pandemic (wild type virus). Eighty percent of patients with acute respiratory disease needed respiratory support, mostly low-flow oxygen therapy. The severity of the disease was similar in all virus variants. Two patients (both with severe comorbidities) died from COVID-related conditions. ConclusionsIn our study, one third of the patients were admitted with SARS-CoV-2 infection but not becauseof it. Acute respiratory disease was less frequent and had a better prognosis compared to the adult population, while MIS-C was a major cause of morbidity and hospitalization. The fatality rate was extremely low.

Assessing severity of COVID-19 and the development of multi system inflammatory syndrome in children (MIS-C) in pediatric patients with atopic disease.

Background: Research surrounding the coronavirus disease 2019 (COVID-19) pandemic and its impact on patients who are atopic has mainly focused on adults. After the delta variant showed increased rates of COVID-19 in children, the pediatric population needs to be assessed as well. Objective: The objective was to assess and report outcomes in patients with COVID-19 and with and without certain atopic diseases in our patient cohort at the University of Mississippi Medical Center. Methods: We conducted a retrospective review of patients by using a de-identified data base that allows querying via medical claims codes from the University of Mississippi Medical Center's Research Data Warehouse. We searched for patients who were COVID-19 positive and ages 0-21 years from January 1, 2020, to December 31, 2021. We then divided this population into two cohorts: an atopic population and a non-atopic population. The incidence of hospitalizations, intensive care unit (ICU) admissions, death, length of stay, inhaled corticosteroid prescription history, and the incidence of multi-system inflammatory syndrome in children (MIS-C) outcomes in the two populations were collected. Results: There were 5261 patients ages 0-21 years and with confirmed COVID-19. After exclusion criteria were applied, there were 1420 patients in the atopic cohort and 2525 patients in the non-atopic cohort. There were more hospitalizations and a longer length of stay in the atopic population. Mortality was equivalent in the atopic and non-atopic populations. There were more ICU admissions in the atopic population. There were 101 patients total with the diagnosis of MIS-C, and the incidence of MIS-C was similar in the atopic and non-atopic populations. There were more patients who were atopic on inhaled corticosteroid than were the patients who were non-atopic. Conclusion: This study sought to further elucidate whether asthma, atopic dermatitis, and allergic rhinitis in pediatric patients was associated with severe COVID-19. Our study showed increased hospitalizations, length of stay, and intensive care in the atopic population but similar outcomes in mortality and the development of MIS-C. Future longitudinal prospective studies are needed to assess the long-term effects on patient's atopic disease after COVID-19 infection.

Investigating Neonatal Multisystem Inflammatory Syndrome Associated with COVID-19 in the Neonatal Intensive Care Unit: A Case Series

Background: The COVID-19 pandemic, caused by the novel SARS-CoV-2 virus, has presented significant challenges to global healthcare systems, affecting individuals of all ages, including neonates. Recent studies have identified a condition similar to Multisystem Inflammatory Syndrome in Children (MIS-C) occurring in neonates, termed MIS-N (Multisystem Inflammatory Syndrome in Neonates), linked to maternal infection with SARS-CoV-2. Understanding MIS-N's clinical manifestations, laboratory findings, and treatment outcomes is crucial for improving neonatal care during the ongoing pandemic. Objective: The objective of this study was to explore the clinical characteristics, laboratory diagnostics, and treatment outcomes of neonates diagnosed with MIS-N, aiming to contribute to better diagnostic and management approaches for this vulnerable population. Methods: This retrospective case series analyzed neonates admitted with suspected MIS-N to the Children's Medical Center in Tehran, Iran, from March to September 2020. Inclusion criteria encompassed neonates showing clinical signs suggestive of MIS-N, elevated inflammatory markers, and positive for SARS-CoV-2 antibodies. Key data points included demographic information, clinical presentation, laboratory results (including complete blood count, inflammatory markers, and specific COVID-19 serology), treatment modalities, and patient outcomes. The effectiveness of interventions was evaluated based on symptom resolution and normalization of lab values. Results: Two neonates were identified with MIS-N. Case I involved a 39-week-old male presenting with diarrhea, dehydration, fever, and a rash, with initial inflammatory markers showing a white blood count (WBC) of 23,000 cells/μL, C-reactive protein (CRP) of 93 mg/L, and serum IgG of 10 g/L. Following treatment with corticosteroids, the patient's condition stabilized, with a decrease in WBC to 18,000 cells/μL and CRP to 34 mg/L. Case II, a 38-week-old female, exhibited a cough, rashes, with WBC of 17,000 cells/μL, CRP of 2 mg/L, and serum IgG of 40 g/L. A single dose of hydrocortisone led to symptom resolution. Both cases had no significant adverse outcomes at a three-month follow-up. Conclusion: Our findings illuminate the clinical and laboratory characteristics of MIS-N in neonates, emphasizing the role of maternal SARS-CoV-2 infection in its etiology. The successful resolution of symptoms with corticosteroid treatment highlights the potential efficacy of this intervention in managing MIS-N. These insights contribute to the growing understanding of MIS-N and underscore the need for ongoing research to define optimal diagnostic criteria and treatment protocols.