Multisystem inflammatory syndrome in children: clinical presentation, management, and short- and long-term outcomes.

OBJECTIVE: In this study, it was aimed to evaluate the demographic, clinical and laboratory characteristics of MIS-C patients in our hospital, to share our treatment approach, and to assess the outcomes of short- and long-term follow-up. METHODS: MIS-C patients who were admitted and treated in our hospital between July 2020 and July 2021 were evaluated. Demographic, clinical, laboratory, and follow-up data were collected from patient records retrospectively. RESULTS: A total of 123 patients with MIS-C (median age, 9.6 years) were included the study. Nineteen (15.4%) were mild, 56 (45.6%) were moderate, and 48 (39%) were severe MIS-C. High CRP, ferritin, pro-BNP, troponin, IL-6, and D-dimer values were found in proportion to the severity of the disease (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, p < 0.001), respectively. Two (1.6%) patients died. The mean follow-up period was 7.8 months. Valve failure, left ventricular dysfunction/hypertrophy, coronary involvement, and pericardial effusion were the most common cardiac pathologies in the short- and long-term follow-up of the patients. In the long-term follow-up, the most common reasons for admission to the hospital were recurrent abdominal pain (14.2%), cardiac findings (14.2%), pulmonary symptoms (8%), fever (7.1%), neuropsychiatric findings (6.2%) and hypertension (3.5%). Neuropsychiatric abnormalities were observed significantly more common in severe MIS-C patients at follow-up (p = 0.016). In the follow-up, 6.2% of the patients required recurrent hospitalization. CONCLUSION: MIS-C is a serious and life-threatening disease, according to short-term outcomes. In addition to the cardiac findings of patients with MIS-C, long-term outcomes such as neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms should be monitored. Key Points • In MIS-C patients, attention should be paid not only to cardiac findings, but also to symptoms related to other systems. • Patients should be followed up in terms of neuropsychiatric findings, persistent gastrointestinal symptoms, fever and pulmonary symptoms that may occur during follow-up.

Delta neutrophil index and C-reactive protein: a potential diagnostic marker of multisystem inflammatory syndrome in children (MIS-C) with COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening hyperinflammation syndrome emerging after COVID-19. The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is evaluated in infection and inflammation. The aim of this study is to evaluate the usefulness of DNI as a diagnostic marker in patients with MIS-C and to assess its role in determining the severity of MIS-C. This retrospective, observational study included 83 patients with MIS-C and 113 patients with COVID-19, and 102 healthy controls. C-reactive protein (CRP), the absolute neutrophil count (ANC), absolute lymphocyte count (ALC), DNI, and the platelet count were recorded. The DNI levels were 4.60 ± 5.70% in the MIS C group, 0.30 ± 0.99% in the COVID group, and 0.20 ± 0.56% in the control group (p < 0.001). According to the severity of MIS-C, the DNI level was found to be 1.22% in mild MIS-C, 4.3% in moderate MIS-C, and 5.7% in severe MIS-C. There was a statistically significant correlation between DNI levels and the severity of MIS-C. The cutoff value of DNI for predicting MIS-C was 0.45%. In the analysis of the diagnostic performance of DNI compared with CRP, ANC, ALC and platelet counts, sensitivity, specificity, positive predictive value, and negative predictive value were found to be 79.5%, 97.1%, 95.7%, and 85.3%, respectively.Conclusions: The delta neutrophil index was identified as a diagnostic marker for MIS-C such as ANC, ALC, platelet count, and CRP. DNI levels in hemogram analysis may guide clinicians in determining the diagnosis and severity of MIS-C. What is Known: • Although CRP, sedimentation, ALC, ANC, platelet count, sodium, and albumin are used as first step tests, there is no specific laboratory marker used in the diagnosis of MIS C. • The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is elevated in infection and inflammation. What is New: • DNI is a promising and easily accessible marker that can be used with other markers in the diagnosis and determines the severity of MIS C. • DNI is an easily accessible, inexpensive, and dynamic marker and its levels in simple hemogram analysis will guide pediatricians in determining the diagnosis and severity in MIS C.

Echocardiographic Findings and Correlation with Laboratory Values in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19.

Cardiac involvement is a common and serious problem in multisystem inflammatory syndrome in children (MIS-C). Echocardiographic evaluation of systolic and diastolic function by traditional, tissue Doppler and three-dimensional (3D) echocardiography was performed in consecutive 50 MIS-C patients during hospitalization and age-matched 40 healthy controls. On the day of worst left ventricular (LV) systolic function (echo-1), all left and right ventricular systolic function parameters were significantly lower (p < 0.001), E/A ratio was significantly lower, and averaged E/e' ratio was significantly higher (median 1.5 vs. 1.8, p < 0.05; 8.9 vs. 6.3, p < 0.001 respectively) in patients compared to control. Patients were divided into 2 groups according to 3D LV ejection fraction (LVEF) on the echo-1: Group 1; LVEF < 55%, 26 patients, and group 2; LVEF ≥ 55%, 24 patients. E/e' ratio was significantly higher in group 1 than group 2 and control at discharge (median 7.4 vs. 6.9, p = 0.005; 7.4 vs. 6.3, p < 0.001 respectively). Coronary ectasia was detected in 2 patients (z score: 2.53, 2.6 in the right coronary artery), and resolved at discharge. Compared with group 2, group 1 had significantly higher troponin-I (median 658 vs. 65 ng/L; p < 0.001), NT-pro BNP (median 14,233 vs. 1824 ng/L; p = 0.001), procalcitonin (median 10.9 vs. 2.1 µg/L; p = 0.009), ferritin (median 1234 vs. 308 µg/L; p = 0.003). The most common findings were ventricular systolic dysfunction recovering during hospitalization, and persisting LV diastolic dysfunction in the reduced LVEF group at discharge. Coronary artery involvement was rare in the acute phase of the disease. Also, in MIS-C patients, the correlation between LV systolic dysfunction and markers of inflammation and cardiac biomarkers should be considered.

Impact of the Novel Coronavirus Disease 2019 (COVID-19) Pandemic on Cardiac Emergencies and Future Perspectives in Turkey

SARS-CoV-2-associated COVID-19 pandemic has affected the daily life of people across the world in 2020. Data about the course of viral involvement continues to be accumulated. COVID-19 is a multi-systemic disease, and the clinical presentations and possible complications may vary widely in different patient groups. The cardiovascular system is a primary target of COVID-19, and direct or indirect effects of viral involvement are observed. In addition to the direct effects of viral involvement on the cardiovascular system, decrement in acute cardiac emergencies has been experienced in many cardiology clinics in Turkey during the pandemic. Moreover, there may be a possible increase in out-of-hospital cardiac arrests in the near future. In this narrative review, we aimed to discuss the cardiac manifestations of COVID-19, the possible drug interactions related to the drugs used for COVID-19 management, and the effect of the pandemic on cardiac emergencies. We believe that understanding the natural mechanism of cardiac involvement of SARS-CoV-2 and emphasizing the data about out-of-hospital arrests will help clinicians effectively deal with the preventable cardiovascular causes of death in the forthcoming waves of COVID-19. [ABSTRACT FROM AUTHOR] Copyright of Erciyes Medical Journal / Erciyes Tip Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Algorithm for the diagnosis and management of the multisystem inflammatory syndrome in children associated with COVID-19.

OBJECTIVE: Although the initial reports of COVID-19 cases in children described that children were largely protected from severe manifestations, clusters of paediatric cases of severe systemic hyperinflammation and shock related to severe acute respiratory syndrome coronavirus 2 infection began to be reported in the latter half of April 2020. A novel syndrome called "multisystem inflammatory syndrome in children" (MIS-C) shares common clinical features with other well-defined syndromes, including Kawasaki disease, toxic shock syndrome and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Our objective was to develop a protocol for the evaluation, treatment and follow-up of patients with MIS-C. METHODS: The protocol was developed by a multidisciplinary team. We convened a multidisciplinary working group with representation from the departments of paediatric critical care, cardiology, rheumatology, surgery, gastroenterology, haematology, immunology, infectious disease and neurology. Our protocol and recommendations were based on the literature and our experiences with multisystem inflammatory syndrome in children. After an agreement was reached and the protocol was implemented, revisions were made on the basis of expert feedback. CONCLUSION: Children may experience acute cardiac decompensation or other organ system failure due to this severe inflammatory condition. Therefore, patients with severe symptoms of MIS-C should be managed in a paediatric intensive care setting, as rapid clinical deterioration may occur. Therapeutic approaches for MIS-C should be tailored depending on the patients' phenotypes. Plasmapheresis may be useful as a standard treatment to control hypercytokinemia in cases of MIS-C with severe symptoms. Long-term follow-up of patients with cardiac involvement is required to identify any sequelae of MIS-C.

Role of Biological Agents in the Treatment of SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: The aims of this study were to evaluate the role of biological agents in the treatment of severe multisystem inflammatory syndrome in children (MIS-C) and to assess the current application, outcomes, and adverse effects in patients who are followed up in a pediatric intensive care unit (PICU). PATIENTS AND METHODS: This observational, descriptive, medical records review study was performed on patients with MIS-C admitted to the PICU between September 1 and November 1, 2020. Through medical records review, we confirmed that patients were positive for current or recent SARS-CoV-2 infection or for COVID-19 exposure history within the 4 weeks before the onset of symptoms. RESULTS: A total of 33 patients with severe MIS-C were included (21 male) with a median age of 9 years. The most common signs and symptoms during disease course were fever (100%) and abdominal pain (75.5%). Clinical features of 63.6% patients were consistent with Kawasaki disease/Kawasaki disease shock syndrome, and 36.4% were consistent with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Myocardial dysfunction and/or coronary artery abnormalities were detected in 18 patients during the PICU stay. Intravenous immunoglobulin and corticosteroids were given to 33 patients. Anakinra was administered to 23 patients (69.6%). There was a significant increase in lymphocyte and platelet counts and a significant decrease in ferritin, B-type natriuretic peptide, and troponin levels at the end of the first week of treatment in patients who were given biological therapy. Two patients were switched to tocilizumab because of an insufficient response to anakinra. The mortality rate of MIS-C patients admitted in PICU was 6.0%. CONCLUSIONS: Management of systemic inflammation and shock is important to decrease mortality and the development of persistent cardiac dysfunction in MIS-C. The aggressive treatment approach, including biological agents, may be required in patients with severe symptoms and cardiac dysfunction.

Therapeutic plasma exchange: A potential management strategy for critically ill MIS-C patients in the pediatric intensive care unit.

This study aimed to evaluate the effectiveness and the role of therapeutic plasma exchange (TPE) in treatment of children with severe MIS-C. In addition, we assessed demographic data, clinical features, laboratory abnormalities, underlying conditions, treatments, and outcomes. Patients with severe MIS-C who were admitted to the pediatric intensive care unit (PICU) between September 01 and October 05, 2020 were included in this observational, descriptive, retrospective study. The data collected included the patients' demographic data, presenting symptoms, clinical features, laboratory parameters, diagnostic investigations, and medications. Of 27 children with MIS-C, 63 % were male. The median age of the patients was nine years. Intravenous immunoglobulin and corticosteroids were used for treatment in 100 % of the patients, anakinra in 51.8 %, vasopressors in 85.1 %, noninvasive mechanical ventilation in 25.9 %, and invasive mechanical ventilation in 18.5 %. Ten of the 27 patients (37 %) underwent TPE. In the patients who underwent TPE, the median PELOD score was 21 (IQR: 11-30.25) before TPE and 10 (IQR: 10-11) after TPE (p < 0.001). Moreover, their median left ventricular ejection fraction (LVEF) was 52 % (IQR: 49.25 %-55 %) before TPE and median LVEF was 66.5 (IQR: 58 %-68.5 %) after TPE (p = 0.012). The median number of TPE sessions was three (IQR: 2-4.75). The mortality rate of the patients with severe MIS-C admitted to the PICU was 7.4 %. We suggest that TPE should be considered as a therapeutic option in children with severe MIS-C. Early initiation of TPE followed by immunomodulatory therapy in critically ill children with MIS-C may help improve clinical and laboratory outcomes.

Comparison of baseline laboratory findings of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis and multisystem inflammatory syndrome in children.

AIMS: Recently, multisystem inflammatory syndrome in children (MIS-C) has been recognized in association with coronavirus disease 2019 as a cytokine storm syndrome. MIS-C presents with symptoms similar to Kawasaki disease and macrophage activation syndrome (MAS). We aimed to better understand this cytokine storm syndrome by comparing the initial laboratory findings of MIS-C and MAS. METHODS: Patients who were diagnosed with MAS due to systemic juvenile idiopathic arthritis in our clinic between March 2002 and November 2020 and with MIS-C between 20 September and 20 October 2020 were enrolled into the study. The medical files of all patients were reviewed retrospectively. RESULTS: A total of 13 MAS (9 boys, 4 girls) and 26 MIS-C (16 boys,10 girls) patients were included in the study. Hemoglobin, absolute neutrophil and lymphocyte counts, C-reactive protein (CRP), ferritin, fibrinogen and lactate dehydrogenase (LDH) levels showed significant differences between the two groups (P < 0.05). Patients with MAS had lower hemoglobin (10.10 g/dL) and fibrinogen (2.72 g/dL), but higher ferritin (17 863 mg/dL) and LDH (890.61 U/L) at the time of diagnosis. Patients with MIS-C had higher absolute neutrophil count (12 180/mm3 ) and CRP (194.23 mg/dL) values, but lower absolute lymphocyte count (1140/mm3 ) at the time of diagnosis. Left ventricle ejection fraction was significantly lower in the MIS-C group in echocardiographic evaluation (P < 0.001). CONCLUSION: Ferritin, hemoglobin, LDH, and fibrinogen levels were significantly changed in MAS compared with MIS-C. However, patients with MIS-C have more severe signs than MAS, such as cardiac involvement.