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In depth characterisation of the proteome of MIS-C and post COVID-19 infection in children reveals inflammatory pathway activation and evidence of tissue damage

Journal of Translational Medicine, 2025

Roarty C., Tonry C., McGinn C., Christie S., Waterfield T., Watson C.

Disease areaApplication areaSample typeProducts
Infectious Diseases
Pathophysiology
Patient Stratification
Plasma
Olink Target 96

Olink Target 96

Olink Explore 3072/384

Olink Explore 3072/384

Abstract

Background

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication that arises between two and six weeks after initial SARS-CoV-2 infection. The mechanisms underlying why only a subset of children develop this hyperinflammatory response remain unclear.

Methods

We performed an in-depth proteomic analysis of plasma samples from children before and after SARS-CoV-2 infection, including those who developed MIS-C. Proteomic profiling was conducted using high-throughput technologies, and findings were validated using publicly available datasets.

Results

Healthy children showed minimal changes in the circulating proteome following SARS-CoV-2 infection, with no evidence of ongoing inflammation. In contrast, children with MIS-C exhibited significant activation of pro-inflammatory pathways and elevated circulating markers of myocardial and vascular injury.

Conclusions

Our data suggest that SARS-CoV-2 infection alone does not cause sustained proteomic alterations in most children. However, MIS-C is associated with a distinct inflammatory and vascular injury signature. Several candidate diagnostic biomarkers for MIS-C were identified and validated in silico, offering promising avenues for future diagnostic and therapeutic strategies.

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