The Genomic and Immunologic Causes Underlying COVID-19 PIMS-TS

NOMIS Research Project

Pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a rare but potentially life-threatening condition. While children have been relatively spared from direct health-related consequences of COVID-19, the emergence of PIMS-TS has demonstrated the unique susceptibility of pediatric age groups. Weeks after asymptomatic COVID-19 infection, children with PIMS-TS classically manifest a febrile disease often accompanied by gastrointestinal symptoms and rash/conjunctivitis, showing similar features to atypical Kawasaki disease. Many children develop shock mimicking toxic shock syndrome, with vasoplegia and cardiac dysfunction as prominent features. Intensive care support for cardiovascular, and sometimes respiratory, as well as the central nervous system and other organ dysfunction is frequently required.

Today, the biological mechanisms resulting in PIMS-TS remain only partially elucidated. Based on current knowledge, PIMS-TS likely results from a multifactorial post-infectious process in which the host immune system mounts an excessive response to persistent COVID-19 antigens, and genetic predisposition is likely to contribute to individual vulnerability.

Severe manifestations due to common infectious pathogens represent very attractive phenotypes to search for rare, causal genetic variants. A recent (February 2021) Policy Brief of the Swiss National COVID-19 Science Task Force stated that “it is imperative that children with PIMS-TS are enrolled in prospective trials where feasible, and that clinical data are collected and shared to improve our understanding of the disease and its best management.”

The Genomic and Immunologic Causes Underlying COVID-19 PIMS-TS project will perform an ancillary basic science study nested within the Swiss RECOVERY-PIMS randomized-controlled trial. Using genome sequencing and immunological analyses, the researchers aim to investigate children’s susceptibility to PIMS-TS. Findings will be compared with an established Swiss cohort on severe bacterial infection (the Swiss Pediatric Sepsis Study) and will contribute to international collaborations on PIMS-TS. This research may help to define better approaches toward untangling disease heterogeneity in pediatric infectious diseases, paving the way toward future personalized therapies.

The project is being led by Luregn Schlapbach at the University Children’s Hospital Zurich (Switzerland).