Pediatric COVID-19 Pathophysiology, immune responses, genetic predispositions, hyperinflammatory syndrome

Children appeared to be initially spared by the SARS-CoV-2 pandemic, however, in spring 2020, a new clinical entity was described related to the SARS-CoV-2 infection and named multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS). The gravity of this inflammatory syndrome, the time interval between infection and MIS-C, the response to the various immunomodulatory treatments are all suggestive of an immunologic reaction rather than a virus-mediatred phenomenon. The pathophysiological mechanisms and possible risk factors for MIS-C have not been elucidated. In this article, we summarize what is known to date about the immune response to SARS-CoV-2 in children and about the immune response to SARSCoV-2 in children and about the MIS-C.

An international registry on COVID-19 related hyperinflammation in children and young adults (HyperPED-COVID)

Introduction: By now, most of the children with COVID-19 infection have only mild symptoms. However, in the past year a small number of children have developed a serious inflammatory condition in temporal association with COVID-19 pandemic. This condition, named Multisystem Inflammatory Syndrome in Children (MIS-C), is characterized by a systemic inflammation with multiorgan failure;the clinical and laboratory features are similar to those usually observed in Kawasaki disease, cytokine storm syndrome and macrophage activation syndrome. While the SARS-CoV-2 PCR on nasal swab is positive only in a minority of patients, the serology is positive in most of them. Objectives: to create an International multicenter collection of patients with MIS-C involving the main pediatric networks committed in the care of patients with hyperinflammatory conditions. Primary endpoint of the project is to collect information on clinical presentation, laboratory parameters, clinical outcome and response to treatment of patients with MIS-C. Secondary endpoints of the project are: 1) to analyse different clusters in clinical phenotype in relation to age and geographical location, 2) to identify clinical and laboratory predictors of disease severity and outcome, 3) to evaluate the availability of samples of patients in the repositories linked to the different centers. Methods: a steering committee constituted by representatives of ERN-RITA, PRES, ESID and ISSAID and with the coordination of PRINTO developed a shared form to collect clinical manifestations, laboratory features, response to treatment and outcome of patients with MIS-C. The registry is available online on PRINTO website (www.printo.it). Results: a first survey between centers members of PRINTO network identified 365 patients from 51 centers (43 countries). Currently, 180 patients have been enrolled in the registry from 25 centers worldwide. Moreover, 11 additional centers have been activated and are ready to start enrollement. Ethical committee submission or activation procedures are ongoing in 36 more centers. 31 European countries and 12 extra-European countries are actively involved. Conclusion: After some interesting national initiatives, the HyperPEDCOVID registry will give the chance to analyze the impact of Multisystem Inflammatory Syndrome Children at the European and extra- European level, giving the possibility to analyze the distribution, clinical presentation and long-term outcome of this condition in different countries. The registry can also represent the basis for further biological and genetic studies in these patients.