[Heart involvement in multisystem inflammatory syndrome in children correlated with SARS-CoV-2 infection: a review by ANMCO/SICP]. / Le manifestazioni cardiache nella sindrome multisistemica infiammatoria del bambino correlate all'infezione da SARS-CoV-2: una rassegna a cura di ANMCO/SICP.

Acute clinical manifestations of COVID-19 are generally less severe in childhood, however a proportion of them can develop a severe systemic hyperinflammatory syndrome after SARS-CoV-2 infection, known as the multisystem inflammatory syndrome (multisystem inflammatory syndrome in children, MIS-C). Cardiovascular manifestations in MIS-C are frequent (34-82%), including myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. The most affected cases can develop cardiogenic shock needing intensive care unit admission, inotropic support and sometimes even mechanical circulatory support. The elevation of myocardial necrosis markers, the frequently transient left ventricular systolic dysfunction and the presence of changes on magnetic resonance imaging, support the hypothesis of an immune-mediated post-viral pathogenesis similar to myocarditis. Although MIS-C shows excellent short-term survival, further studies are needed to demonstrate complete reversibility of residual subclinical heart damage.

Multiorgan Inflammatory Syndrome in Adults MIS-A Post SARS-CoV-2 Infection: A Novel Clinical Enigma.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is an emergent heterogenous clinical syndrome seen in the convalescent phase of COVID-19 infection. MIS in children (MIS-C) is a rare but severe post-COVID-19 illness that has been recognized by the WHO and the Centre for Disease Control and Prevention (CDC). It introduced a similar illness in adults based on multiple case series, identified as MIS-A. OBJECTIVE: We present four rare cases of multiorgan inflammatory syndrome in adults (MI-A) presented in Goa Medical College (Tertiary Medical Institute). We would like to highlight the diversity of presentation of symptoms with a significant history of previous covid infection, laboratory abnormalities, the clinical course of the disease, treatment strategies, and response and follow-up findings. We seek to highlight the emergence of a serious clinical entity that can be fatal if not diagnosed or treated promptly. MATERIALS AND METHODS: This was a descriptive study conducted in Goa Medical College from June 2021 to November 2021. A systematic search in the Department of General Medicine, the Department of Medical Records, and data from ICU, ITU, and critical covid wards were collected. RESULTS AND CONCLUSION: A total of four cases fulfilling the criteria for MIS-A as per MMWR (CDC 2020)were included, ranging from the age group of 29-70 years. All had features of severe systemic inflammatory response with multiple organ dysfunction and elevated proinflammatory markers. All four patients had a recent history of (mild) COVID-19 infection. Hence, in the current pandemic scenario, MIS-A should be considered as a possible diagnosis in patients with recent COVID infection presenting with MODS, when the obvious septic cause is excluded through thorough clinical, physical, serological, laboratory, and radiological investigations. However, the presence of a past covid infection may not be an absolute criterion due to mild symptoms of the primary covid infection which usually go unnoticed resulting in nontesting.

Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.

BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

Multisystem inflammatory syndrome in children associated with COVID-19 presenting as cervical inflammation.

AIM: The major clinical manifestations multisystem inflammatory syndrome in children (MIS-C) are fever, gastrointestinal and cardiac. The aim of this study was to describe MIS-C in a series of patients who presented primarily with cervical manifestations. METHODS: We retrospectively reviewed medical records of all patients who met the Centers for Disease Control and Prevention and World Health Organization MIS-C diagnostic criteria treated at Hadassah-Hebrew University Medical Center between April 2020 and September 2021. RESULTS: Of 37 children diagnosed with MIS-C (median age: 10.2 years, range 1.5-18 years, 20 male) five, 13.5% (median age: 14.4 years, range 9.2-17.5 years) presented with cervical symptoms mimicking neck infections. One was hospitalised with a working diagnosis of retropharyngeal abscess, and four with acute cervical lymphadenitis that did not respond to early antibiotic treatment. All developed full MIS-C phenotype. CONCLUSION: MIS-C may present as cervical inflammation. An ill-appearing child with symptoms and/or signs of cervical inflammation should be evaluated for clinical and laboratory features of MIS-C, thereby facilitating prompt treatment of this potentially fatal disorder.

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Bilateral keratouveitis associated with COVID-19 multisystem inflammatory syndrome in children.

We report the case of a 16-year-old girl admitted to hospital with multisystem inflammatory syndrome in children (MIS-C) secondary to COVID-19. Conjunctivitis-like symptoms prompted ocular examination, which demonstrated peripheral confluent corneal opacities and anterior uveitis. Uveitis laboratory investigations were negative, and with topical steroid treatment her signs and symptoms resolved completely. These features may be overlooked in the setting of MIS-C, where patients are systemically unwell and are typically examined at the bedside.

Cardiac Outcome of Children With SARS-CoV-2 Related Multisystem Inflammatory Syndrome.

OBJECTIVE: To study the cardiac outcomes of patients with multisystem inflammatory syndrome in children (MIS-C) after 6-month of diagnosis. METHODS: This review of hospital records was conducted on MIS-C patients (aged <21 year) who completed a six-month follow up. The baseline demographic, clinical, laboratory, and treatment characteristics during the acute phase, and echocardiographic findings during follow-up were collected. RESULTS: 116 patients (61.2% male, median age 7 years) with MIS-C were included in the study. At the time of admission, cardiac abnormalities were present in 70.7% of MIS-C patients, and the most common cardiac abnormalities were valve failure (50.9%), followed by ventricular dysfunction (39.7%), and pericardial effusion (23.3%). Six month after diagnosis, cardiac abnormalities were found in 10.3% of patients, and patients had lower rates of ventricular dysfunction (P<0.001), valve failure (P<0.001), pericardial effusion (P<0.001), and coronary involvement (P<0.001) as composed to the baseline. Intravenous immunoglobulin (IVIG) and steroid treatment significantly reduced the odds of occurrence of ventricular dysfunction (P=0.002), valve failure (P=0.004), and low ejection fraction (P=0.002) in comparison to IVIG treatment. CONCLUSION: While most MIS-C patients had abnormal echocardiographic findings at admission, only 10.3% of patients had cardiac abnormalities during follow up.

A unilateral whiteout lung in child with multisystem inflammatory syndrome associated with COVID-19 due to SARS-CoV-2: one case report of a boy.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a relatively new and rare complication of COVID-19. This complication seems to develop after the infection rather than during the acute phase of COVID-19. This report aims to describe a case of MIS-C in an 8-year-old Thai boy who presented with unilateral lung consolidation. Unilateral whiteout lung is not a common pediatric chest radiograph finding in MIS-C, but this is attributed to severe acute respiratory failure. CASE PRESENTATION: An 8-year-old boy presented with persistent fever for seven days, right cervical lymphadenopathy, and dyspnea for 12 h. The clinical and biochemical findings were compatible with MIS-C. Radiographic features included total opacity of the right lung and CT chest found consolidation and ground-glass opacities of the right lung. He was treated with intravenous immunoglobulin and methylprednisolone, and he dramatically responded to the treatment. He was discharged home in good condition after 8 days of treatment. CONCLUSION: Unilateral whiteout lung is not a common pediatric chest radiographic finding in MIS-C, but when it is encountered, a timely and accurate diagnosis is required to avoid delays and incorrect treatment. We describe a pediatric patient with unilateral lung consolidation from the inflammatory process.

Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated autoimmune-mediated illness in genetically susceptible patients following COVID-19 with an interval of 2-6 weeks. The median age of patients with MIS-C is 6-11 years. Most common manifestations are involvement of gastrointestinal tract, cardiovascular system, hematological system, and mucocutaneous system. Respiratory tract, neurological system, musculoskeletal system, and kidney are less frequently affected. Mucocutaneous manifestations and coronary artery abnormalities characteristic for Kawasaki disease (KD) may be observed in a significant proportion of MIS-C patients that may make the differential diagnosis be difficult for some patients, especially in the post-pandemic era. The mortality rate is 1-3%. Management and prognosis of MIS-C are similar to that of KD. MIS-C and KD may share a common pathogenic process. Based on the observation of MIS-C-like illness in uninfected neonates, i.e. multisystem inflammatory syndrome in neonates, both MIS-C and KD may be a consequence of dysregulated, over-exaggerated humoral immune responses triggered by a specific infectious agent.

Multicolored MIS-C, a single-centre cohort study.

BACKGROUND: The aim of this study was to investigate the clinical and laboratory parameters that can predict the severity of Multisystem Inflammatory Syndrome in Children (MIS-C) at admission. METHODS: We conducted a single-center, partly retrospective, partly prospective, observational cohort study between November 1, 2020 and December 31, 2021, which included patients aged from 1 month to 19 years, meeting the diagnostic criteria of MIS-C. We categorized the patients into three subgroups based on clinical and laboratory markers and assessed the predictive value of these factors in terms of ICU administration and cardiac abnormalities. RESULTS: 53 patients were classified in the following subgroups: Kawasaki-like disease (group 1) (47.2%, n = 25), shock with or without acute cardiac dysfunction (group 2) (32%, n = 17), fever and inflammation (group 3) (20.8%, n = 11). Subgroup analysis revealed that patients with shock and KD at initial presentation had significantly more severe manifestation of MIS-C requiring intensive care unit (ICU) treatment. Of the initial laboratory values, only CRP showed a significant difference between the 3 clinical groups, being lower in group 3. 52.6% of patients were admitted to the ICU. The median length of ICU stay was 3 days (range 3-20). ICU admission was more likely in patients with shortness of breath, renal failure (AKI) and patients with significantly increased concentrations of ferritin, D-dimer, INR and significantly milder increase concentration of fibrinogen. We found that fibrinogen and ferritin levels are independent risk factors for ICU admission. Cardiac abnormalities were found in 56.6% of total (30/53), with the following findings: decreased left ventricular function (32%), coronary abnormality (11.3%), pericardial effusion (17%), arrhythmia (32.1%) and mitral regurgitation (26.6%). Diarrhea and conjunctivitis at the initial presentation with significantly elevated CRP, Pro-BNP and blood pH concentrations were found to be a potential predisposing factor for decreased cardiac function while Pro-BNP and pH were independent risk factors for MIS-C. Regardless of the initial symptoms of MIS-C, the outcome was generally favorable. CONCLUSIONS: Clinical characteristics and baseline laboratory values ​​may help identify patients at increased risk for severe disease outcome, such as need for intensive care, presence of shock and decreased cardiac function. TRIAL REGISTRATION: Participation consent was not reqired and ethical considerations were unnecessary, since we did not perform any extra interventions, only the necessary and usual therapeutic and diagnostic methods were used.

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: A Spectrum of Postinfectious Hyperinflammatory Disease.

Kawasaki disease and multisystem inflammatory syndrome in children are hyperinflammatory conditions that share similar emerging pathophysiology hypotheses, clinical features, treatment strategies, and outcomes. Although both conditions have key differences, growing evidence suggests that both conditions might be closely related on a larger spectrum of postinfectious autoimmune responses.

Multisystem inflammatory disease in neonates (MIS-N) due to maternal COVID-19.

Multisystem inflammatory disease in neonates (MIS-N) is a disease of immune dysregulation presenting in the newborn period. Thouvgh its etiopathogenesis is proposed to be similar to multisystem inflammatory disease in Children (MIS-C), the exact pathophysiology is largely unknown as of present. The definition of MIS-N is contentious. The evidence for its incidence, the clinical features, profile of raised inflammatory markers, treatment strategies and outcomes stem from case reports, case series and cohort studies with small sample sizes. Though the incidence of MIS-N in severe acute respiratory syndrome caused by the coronavirus CoVID-2 (SARS-CoV-2) infected asymptomatic neonates is low, its incidence in symptomatic neonates is relatively higher. Further, amongst the neonates who are treated as MIS-N, the mortality rate is high. The review also evaluates the various other unresolved aspects of MIS-N from limited published literature and identifies knowledge gaps which could be areas of future research.

The Role of Mean Platelet Volume in Multisystem Inflammatory Syndrome in Children With Cardiac Manifestations.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a novel pediatric disorder associated with coronavirus disease 2019. However, no laboratory parameters can diagnose MIS-C. This study aimed to determine the changes in mean platelet volume (MPV) and investigate its relationship with cardiac involvement in MIS-C. METHODS: In this single-center retrospective study, 35 children with MIS-C, 35 healthy children and 35 febrile children were enrolled. Patients with MIS-C were further subdivided depending on the presence of cardiac involvement. For all patients, the white blood cell, absolute neutrophil, absolute lymphocyte, platelet counts, MPV and C-reactive protein levels were recorded. Ferritin, D-dimer, troponin and CK-MB levels and the day when IVIG was administered were recorded and compared between groups. RESULTS: Thirteen patients with MIS-C had cardiac involvement. The mean MPV of the MIS-C group was significantly higher than those of the healthy ( P = 0.0001) and febrile ( P = 0.027) groups. Using a cutoff of >7.6 fL, the MPV had a sensitivity of 82.86% and specificity of 82.75%, and the area under the MPV receiver operating characteristics curve was 0.896 (0.799-0.956). The MPV was significantly higher in patients with cardiac involvement than in those without ( P = 0.031). Logistic regression analysis revealed that the association between the MPV and cardiac involvement was significant (odds ratio, 2.28; 95% confidence interval, 1.04-2.95; P = 0 .039). CONCLUSIONS: The MPV may indicate cardiac involvement in patients with MIS-C. Large cohort studies are needed to define an accurate cutoff value for the MPV.

Clinical-laboratory profile of children and adolescents with multisystem inflammatory syndrome temporarily associated with COVID-19 in Goiás, Brazil.

Here, we describe the clinical and laboratory characteristics of patients diagnosed with multisystem inflammatory syndrome in children (MIS-C) in the state of Goiás, Brazil, and its possible association with COVID-19. The study subjects were individuals aged between 0 and 19 years, selected from private and public institutions from May 2020 to April 2022. Thirty-five cases of MIS-C were confirmed. Four progressed to death. Most of the patients were 0-9 years old. All had fever, and 71.4% had abdominal pain. All had elevated levels of inflammatory markers, and 40.0% were positive for SARS-CoV-2 by RT-PCR. This study demonstrates a broad relationship between MIS-C and SARS-CoV-2 infection. Further studies are needed to confirm this association.

Expanding the Differential for Alternative Diagnoses in the Workup of Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome associated with SARS-CoV-2 infection. Children are increasingly admitted for MIS-C evaluation, but instead found to have alternative diagnoses. METHODS: Retrospective study of all pediatric patients <21 years of age hospitalized between August 1, 2020, and July 31, 2021, with clinical concern for MIS-C at the time of presentation were identified through use of an institutional computerized MIS-C order entry set. Final diagnoses were then collected through primary review of the medical record from the time of initial presentation through 1-month postdischarge. RESULTS: Of 359 cases identified through the MIS-C order entry set, 126 (35.1%) met criteria for MIS-C, 28 had Kawasaki Disease (KD) (7.8%), and 11 cases met criteria for both MIS-C and KD (3.1%), leaving 194 (54.0%) patients ruled out and categorized as "MIS-C mimickers." Infectious diagnoses were the most common MIS-C mimickers (78.9%). Of the infectious etiologies, bacterial (51.0%) and viral (52.3%) etiologies were seen with similar frequency. CONCLUSIONS: We describe MIS-C mimickers spanning multiple subspecialties, with infectious etiologies predominating, which can aid clinicians in the consideration of diagnostic testing, with the goal of achieving timely and accurate diagnoses.

Can Serum 25-Hydroxy Vitamin D Levels Predict the Severity of Multisystem Inflammatory Syndrome in Children and COVID-19?

Objective: To determine the clinical significance of serum 25-hydroxy (OH) vitamin D levels in pediatric patients with multisystem inflammatory syndrome in children (MIS-C) and compare the vitamin D levels of these patients with those patients with Coronavirus disease-2019 (COVID-19) and healthy controls. Methods: This study was designed for pediatric patients aged 1 month to 18 years and conducted between July 14 and December 25, 2021. Fifty-one patients with MIS-C, 57 who were hospitalized with COVID-19, and 60 controls were enrolled in the study. Vitamin D insufficiency was defined as a serum 25 (OH) vitamin D level of less than 20 ng/mL. Severe MIS-C was classified as necessitating intensive care due to cardiovascular instability, the necessity for non-invasive or invasive mechanical ventilation, and/or a diminishing Glasgow coma scale. World Health Organization definition criteria were used to describe the clinical stages of COVID-19 in children and patients were divided into four groups according to the clinical severity of COVID-19: asymptomatic, mild, moderate, and severe/critical. Results: The median serum 25 (OH) vitamin D was 14.6 ng/mL in patients with MIS-C, 16 ng/mL in patients with COVID-19, and 21.1 ng/mL in the control group (p<0.001). Vitamin D insufficiency was present in 74.5% (n=38) of patients with MIS-C, 66.7% (n=38) of patients with COVID-19, and 41.7% (n=25) of the controls (p=0.001). The percentage of four or more affected organ systems was 39.2% in patients with MIS-C. The correlation between the number of affected organ systems and serum 25 (OH) vitamin D levels was evaluated in patients with MIS-C and there was a moderate negative correlation (r=-0.310; p=0.027). A weak negative correlation was found between the severity of COVID-19 and serum 25 (OH) vitamin D (r=-0.320, p=0.015). Conclusion: Vitamin D levels were insufficient in both the MIS-C and COVID groups. Furthermore, vitamin D levels correlated with the number of affected organ systems in MIS-C and the severity of COVID-19.