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.

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.