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.

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.

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.