Cytokine Profile in Children with Severe Multisystem Inflammatory Syndrome Related to the Coronavirus Disease 2019.

The multisystem inflammatory syndrome in children (MIS-C) is a novel and concerning entity related to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Although MIS-C has been the subject of intensive research efforts, its pathophysiology and optimal treatment remain elusive. We studied the clinical features, laboratory findings, and immunoinflammatory profiles of seven children prospectively admitted to a pediatric intensive care unit (PICU) during the first wave of the pandemic. All patients had immunoglobulin (Ig)-G against SARS-CoV-2, four of seven patients had both IgM and IgG, and in one of the 7 SARS-CoV-2 was detected in a respiratory sample. All patients received intravenous fluid boluses (median: 15 mL/kg) and norepinephrine. The most common form of respiratory support was supplemental oxygen via nasal cannula. None of the patients needed mechanical ventilation. The cardiovascular system was frequently involved. All patients had an elevated troponin-I (median: 107.3 ng/L). Four out of seven patients had coronary artery abnormalities, and two of seven had both abnormal electrocardiogram (EKG) findings and evidence of left ventricular dysfunction on echocardiogram. Ig levels and complement function were normal. Peripheral blood phenotyping with flow cytometry showed decreased T-cell numbers at the expense of CD8+ T-cells. Cytokine profiling showed a heterogeneous increase in interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-18, IL-2Ra, IL-10, and IL-1Ra that tended to normalize after treatment. Our study shows that children with MIS-C have elevated plasma levels of pro- and anti-inflammatory cytokines in the acute phase of the disease without other relevant immunologic disturbances. These findings suggest the presence of a mixed antagonist response syndrome (MARS) similar to that present in pediatric sepsis. Combining a meticulous differential diagnosis with cautiously coordinated immunomodulatory therapy and high-quality supportive care can help clinicians avoid causing iatrogenic harm in patients with MIS-C.

Candidemia Diagnosis With T2 Nuclear Magnetic Resonance in a PICU: A New Approach.

OBJECTIVES: Early diagnosis of invasive Candida infections is a challenge for pediatricians, intensivists, and microbiologists. To fill this gap, a new nanodiagnostic method has been developed using manual application of T2 nuclear magnetic resonance to detect Candida species. The aim of this study was to evaluate, prospectively, the usefulness as a tool diagnosis of the T2Candida panel in pediatric patients admitted at the PICU compared with blood culture. DESIGN: This is a prospective, observational, and unicentric study to compare T2Candida results with simultaneous blood cultures for candidemia diagnose. SETTING: This study was carried out in a 1,300-bed tertiary care hospital with a 16-bed medical-surgical PICU. PATIENTS: Sixty-three patients from 0 to 17 years old were enrolled in this study, including those undergoing solid organ transplantation (kidney, liver, pulmonary, multivisceral, intestinal, and heart) and hematopoietic stem cell transplantation. MEASUREMENTS AND MAIN RESULTS: Seven patients were positive by the T2Candida test. Only two of them had the simultaneous positive blood culture. T2Candida yielded more positive results than blood cultures. CONCLUSIONS: T2Candida might be useful for the diagnosis of candidemia in PICUs. The prevalence of candidemia might be underestimated in this pediatric population. The use of this diagnostic tool in these units may help clinicians to start adequate and timely antifungal treatments.

Fatal outcome of anti-MDA5 juvenile dermatomyositis in a paediatric COVID-19 patient: a case report.

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.