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Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vβ21.3 T cell receptor β chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vβ21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vβ21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

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BackgroundAsthma is the most common obstructive airway disease in children and adults. Nasal high flow (NHF) is a recent device that is now used as a primary support for respiratory distress. Several studies have reported use of NHF as a respiratory support in status asthmaticus; however, there are no data to recommend such practice. We therefore conducted this preliminary study to evaluate NHF therapy for children with status asthmaticus admitted to our PICU in order to prepare a multicentre randomized controlled study.ResultsBetween November 2009 and January 2014, 73 patients with status asthmaticus were admitted to the PICU, of whom 39 (53%) were treated with NHF and among these 10 (26%) presented severe acidosis at admission (pH < 7.30). Thirty-four less severe children (41%) were treated with standard oxygen. For one child (2.6%) NHF failed and was then switched to non-invasive ventilation. NHF was discontinued in another patient because of the occurrence of pneumothorax after 31 h with NHF; the patient was then switched to standard oxygen therapy. Mean ± SD heart rate (165 ± 21 vs. 141 ± 25/min, p < 0.01) and respiratory rate (40 ± 13 vs. 31 ± 8/min, p < 0.01) decreased significantly, and blood gas improved in the first 24 h. In the subgroup of patients with acidosis, median [IQR] pH increased significantly between hour 0 and 2 (7.25 [7.21–7.26] vs. 7.30 [7.27–7.33], p = 0.009) and median [IQR] pCO2 decreased significantly (7.27 kPa [6.84–7.91 vs. 5.85 kPa [5.56–6.11], p = 0.007). No patient was intubated.ConclusionThis retrospective study showed the feasibility and safety of NHF in children with severe asthma. Blood gas and clinical parameters were significantly improved during the first 24 h. NHF failed in only two patients, and none required invasive ventilation.