Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal presentation. Intravenous immunoglobulin (IVIG) is recommended as first line therapy in KD. Recent evidence suggests intravenous immunoglobulins (IVIG) resistance in some cases of SARS-CoV-2 related MIS-C, thereby questioning the benefit of immunomodulators such as IL-1 or IL-6 blocking agents. We report on a cohort of 6 Swiss children with SARS-CoV2 related MIS-C presenting with clinical features compatible with Incomplete KD and Toxic Shock Syndrome associated to a cytokine storm. Serum cytokine profile investigations showed increased IL1RA levels (8 to 22-fold) in 5 of the 6 patients (one patient had not been tested), whereas, IL-6 serum levels were increased only in the 3 patients of the 6 who were tested. With exception of one patient who had only benefited by Anakinra, all patients received at least one dose of IVIG. One patient has only received Anakinra with favorable evolution, and three patients had also a steroid treatment. In addition to all this anti-inflammatory medication two patients have also received one dose of anti-IL6. In conclusion, our case series reports on clinical and laboratory findings of most of Swiss cases with MIS-C and suggests the use of Anakinra as an alternative to steroids in these children, most of whom presented with high IL-1RA levels.

This study aimed to investigate the association of IL-1RA VNTR and IL-1α 4845G>T polymorphisms with idiopathic male infertility followed by an in silico analysis. In a case-control study, we collected blood samples from 230 infertile and 230 healthy men. Genotyping of IL-1RA VNTR was performed by PCR whereas IL-1α 4845G>T was genotyped by polymerase chain reaction-restriction fragment length polymorphism. An in silico approach was employed for the detection of IL-1RA VNTR and IL-1α 4845G>T effects on some molecular aspects of IL-1RA and IL-1α respectively. The result of our genetic association study for IL-1α 4845G>T revealed that there was a significant association between GT genotype, TT genotype, T allele and idiopathic male infertility. Although there was no significant association between IL-1RA VNTR and male infertility in the overall analysis. However, subgroup analysis revealed that the subjects with VNTR 4R/5R genotype were at a higher risk of oligozoospermia. Furthermore, 4845TT genotype, and 4845T allele were associated with oligozoospermia, asthenozoospermia and nonobstructive azoospermia. Bioinformatics analysis showed that IL-1RA VNTR may affect the splicing pattern of IL-1RA. Moreover, IL-1α 4845G>T has a significant effect on RNA structure and protein function. Based on our findings, both IL-1RA VNTR and IL-1α 4845G>T polymorphisms could be considered as potential biomarkers for screening of susceptible individuals.