Diagnosis of MIS-C in febrile children

PROJECT SUMMARYThe recent emergence of SARS-CoV-2 and resultant pandemic of COVID-19 disease has overwhelmed globalhealth systems and led to over 200,000 American deaths to date. While initial reports suggested that SARS-CoV-2 infection in children was generally benign, a novel post-inflammatory syndrome known as multisysteminflammatory syndrome in children (MIS-C) has now been described. MIS-C in children is characterized by fever,systemic inflammation, and end-organ involvement, and the majority of patients are IgG seropositive for SARS-CoV-2. Because the clinical features of MIS-C overlap with other infections and inflammatory disorders, newstrategies for diagnosis of MIS-C in febrile children are urgently needed. Our immediate objective (during theR61 phase) is to determine the reproducible changes in breath, urine, and salivary volatile composition in chil-dren diagnosed with MIS-C. We will integrate these discovery studies with clinical and immunological profiling todevelop (during R61 phase) and validate (during R33 phase) a novel and much-needed MIS-C diagnostic, whichis expected to have a major impact on care of febrile children. Our long-term goal to develop a diagnostic strategyto distinguish children with MIS-C from children with other causes of fever. Supported by our strong preliminarydata that indicate our expertise and feasibility of this strategy, our objectives will be met through three specificaims: 1) Characterize breath biomarkers in children with MIS-C (R61); 2) Relate breath VOC changes to virolog-ical, disease severity, and immunological features of MIS-C (R61); and 3) Validate our novel MIS-C diagnosticfor clinical use (R33). The proposed research is significant, because we will progress in development of new,much-needed MIS-C rapid diagnostic tool.