Introduction
Early in the COVID-19 pandemic, children and adolescents were thought to be important transmitters of the disease but were also believed to be only mildly affected.1 Later, evidence increased that children are not major spreaders.2,3,4 However, reports of a multiorgan immune syndrome in children and youths surfaced from Italy, the UK and the US,5 occurring weeks to months after the SARS-CoV-2 wave. Studies in clinical settings6 and assessments of registry data from different countries followed,7 and suggested the association of the multiorgan immune syndrome and SARS-CoV-2 infections in children and youths.
The syndrome was named pediatric multiorgan immune syndrome (PMIS), pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) or multiorgan immune syndrome in children (MIS-C). It features many characteristics of the Kawasaki disease but it also showed some peculiar differences. PMIS ranges from 3 to 17 years while Kawasaki disease usually presents before the age of 5 years. Cardiac dysfunction and shock as well as gastrointestinal and neurologic symptoms are more frequent in PMIS.8 Interestingly, an association of Kawasaki disease with coronavirus infections has been discussed even before the COVID-19 pandemic.9
Recent studies linked PMIS to the presence of antibodies to SARS-CoV-2 and some authors suggested that high levels of antibodies against SARS-CoV-2 may in fact contribute to the occurrence of the syndrome.10 However, these observations were based onpost hoc measurements of antibodies in children who had already acquired PMIS and had been hospitalized for severe symptoms.
We speculated that if strong antibody responses occur in children after SARS-CoV-2 infection, which could be causal for the onset of PMIS, they should be present before PMIS manifests or while the disease is still mild and thus, could be used to detect those children at risk to develop severe PMIS. Thus, we to screen a large number of children in rather severely affected areas of Bavaria (Southern Germany) for neutralizing and overall antibody levels against SARS-CoV-2 in the first pandemic wave. Children with significantly elevated antibody responses were evaluated clinically for signs of PMIS using a three-stage work-up protocol.