Cell Injury Biomarker Identified in Children with Multisystem Inflammatory Syndrome

By Rebecca Araujo - April 26, 2023

New data from a study funded by the National Institutes of Health reported that children with multisystem inflammatory syndrome (MIS-C) have a distinct biomarker that is not present in other children with COVID-19. MIS-C is a rare condition linked with SARS-CoV-2 infection that is marked by external and internal inflammation.

The study, which was published in Cell Reports Medicine, was conducted by Charles Y. Chiu, MD, of the University of California San Francisco, and colleagues from other institutions. The investigators used next-generation sequencing to analyze 416 blood samples from 141 children diagnosed with MIS-C and 70 children with acute COVID-19. Additionally, 26 controls were included in the study.

After analysis with plasma cfRNA profiling, the researchers identified signatures associated with cell injury and cell death that distinguished between patients with MIS-C and acute COVID-19. wbRNA analysis showed overlap in pro-inflammatory pathways between samples with MIS-C and COVID-19, as well as pathways specific to the respective disease states. Based on plasma cfDNA methylation profiling, patietns with MIS-C had increased cfDNA and solid organ involvement compared with patients with COVID-19 and controls. Upon comparative analysis, the investigators found that cfRNA and wbRNA samples yielded separate, but complementary signatures associated with MIS-C and COVID-19.

“These results provide novel insights into the differential pathogenesis of MIS-C and COVID-19. They also lay the groundwork for the development of minimally invasive gene expression based diagnostic tests that can differentiate MIS-C other hyperinflammatory states, including septic shock, Kawasaki disease, severe COVID-19 with systemic involvement, and toxic shock syndrome,” wrote the authors.

Furthermore, the results “underscore the potential utility of cfRNA and cfDNA biomarkers for evaluating tissue injury and monitoring recovery.”

The researchers acknowledge several limitations to the study, such as a low sample size of patients with asymptomatic-to-mild COVID-19, longitudinally collected samples, and limited controls. They also noted that demographic distribution was not uniform in this analysis, limiting the application of these findings.

“Previous studies have shown that non-Hispanic Black children are at a higher risk of MIS-C as compared to other children infected with COVID-19, suggesting differential immune responses, although phenotype comparisons identified no racial or ethnic differences” in this study, the authors noted. “Further studies incorporating additional samples and representative sampling are needed to address these limitations.”

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