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.

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7–59 months in a population with suboptimal vaccination coverage of 55%.MethodsThe study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI).Results169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1–87.2) and 90% (95% CI, 63.9–97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7–97.9) against serotype 1 and 86.0% (95% CI, 51.2–99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8).ConclusionsThe effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7–59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually.