Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that: 1) MIS-C and pre-pandemic KD cytokine profiles may be unique and justify the clinical differences observed; 2) SARS-CoV-2-specific immune complexes (IC) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 MIS-C; 9 patients with positive SARS-CoV-2-PCR without MIS-C (COVID); 14 pre-pandemic KD and 37 healthy controls (HC). Thirty-four circulating cytokines were quantified in pre-treatment serum or plasma samples and the presence of circulating SARS-CoV-2 IC was evaluated in MIS-C patients.Compared to HC, MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ-induced response markers (including IFN-γ, IL-18, IP-10) and inflammatory monocytes activation markers (including MCP-1, IL-1α, IL-1RA) being the main triggers of inflammation. With linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-C plus ) differentiated from the remaining MIS-C patients in IFNγ, IL-18, GM-CSF, RANTES, IP-10, IL-1α and SDF-1 and incipient signs of macrophagic activation syndrome. Circulating SARS-CoV-2-IC were not detected in MIS-C patients. Our findings suggest a major role of IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.
Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children. Methods This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March–June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes. Results Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded. All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3–41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5–14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin. All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5–30). The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively). Conclusions Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.
During the pandemic caused by the novel coronavirus (COVID-19), lung ultrasound has been used to diagnose and monitor respiratory condition. The aim of the study was to describe lung ultrasound findings in children with a COVID-19 infection. Patients younger than 18 years old and positive for COVID-19, admitted to pediatric tertiary referral hospital were included. They were divided into two groups depending on the presence of respiratory symptoms. Lung ultrasound results were categorized into four degrees according to Soldati et al. score (J Ultrasound Med 39:1–7, 2020 ) and it was also described the presence and type of consolidation. Sixteen patients were recruited. The median age was 11 years old (IQR 2.8–12). Four children (25%) required admission to the intensive care unit. Six patients (37.5%) presented with respiratory symptoms. Most of them showed S.score of 2 and subpleural consolidations were observed in four cases (66.6%). Ten patients (62.5%) presented with non-respiratory symptoms, lung ultrasound showed S.score from 0 to 2. Three (30%) were diagnosed of multisystem inflammatory syndrome and lung ultrasounds showed S.score of 2 with bilateral pleural effusion. Conclusions : Children with COVID-19 and respiratory symptoms mostly showed a S.score of 2 and 3 with subpleural consolidations, upon the lung ultrasound assessment. What is Known : • Lung ultrasound is a useful tool for monitoring patients with respiratory symptoms in both adults and children. Lung ultrasounds are altered in adult patients with COVID-19. What is New : • Lung ultrasound might improve COVID-19 assessment, it could be a useful tool to diagnose and monitor patients throughout the COVID-19 pandemic. Even COVID-19 patients with non-respiratory symptoms have lung alterations that are visible on lung ultrasound. Electronic supplementary material The online version of this article (10.1007/s00431-020-03839-6) contains supplementary material, which is available to authorized users.
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