Identification of Gene Signatures Associated with Multisystem Inflammatory Syndrome in Children after SARS-CoV-2 Infection

Introduction: Children with Coronavirus Disease 2019 (COVID-19) and those with Multisystem Inflammatory Syndrome in Children (MIS-C) exhibit similar inflammatory responses, yet distinct differences exist, particularly in immune cell reactions. This study aimed to uncover the differences between them. Methods: This study analyzed plasma cell-free ribonucleic acid cfRNA and whole blood RNA wbRNA from children with COVID-19, MIS-C, and a healthy control group. Pediatric blood and plasma samples were collected from three hospital systems, including patients with PCR-confirmed COVID-19 and those meeting CDC-defined criteria for MIS-C. COVID-19 cases required SARSCoV- 2 positivity within 14 days of sampling, while MIS-C diagnoses were adjudicated by multidisciplinary teams based on clinical and inflammatory features. Each sample was represented by 60,708 gene expressions. Ten advanced feature ranking algorithms were first applied to yield feature lists. Then, these lists were analyzed by incremental feature selection method, which contained four classification algorithms and synthetic minority oversampling technique, to extract essential genes and build efficient prediction models and classification rules. Results: Several important genes were discovered, which were identified by multiple feature ranking algorithms. The optimal models on cfRNA and wbRNA achieved weighted F1 scores exceeding 0.9. Discussion: Analysis of the cfRNA dataset revealed low EPSTI1 expression and low SNHG6 expression in MIS-C patients, while the wbRNA dataset indicated high IFI27 expression in COVID-19 patients and high JUN expression in COVID-19 and MIS-C patients compared with noninflammatory controls. Conclusion: The newly found genes can serve as potential qualitative markers for COVID-19 or MIS-C.