COVID-19 in children: a prospective study investigating host response to SARS-CoV-2.

Initially, MIS-C cases required intensive care, with multiple organs affected, particularly the heart and vasculature. The cause and long-term outcomes of MIS-C were unclear, and no diagnostic tests were available.The first part of this thesis reports on the clinical characteristics and potential risk factors for severe disease in a cohort of MIS-C cases from Northern Ireland, providing one of the first studies on long-term outcomes following discharge.The second part applies discovery proteomics to investigate the proteome of children with MIS-C, identifying biological pathways driving the disease, such as chemokine signalling, platelet activation, and complement activation.

Comparison with healthy children post-SARS-CoV-2 infection and febrile controls revealed distinct proteomic differences, highlighting pathways uniquely involved in MIS-C, including IFN-γ activation and extracellular matrix organization. Candidate diagnostic biomarkers for MIS-C were identified from proteomic data and verified in the MIS-C cohort, showing potential for distinguishing MIS-C from other febrile illnesses.Finally, the leading hypothesis that increased intestinal permeability allows persistent SARS-CoV-2 spike protein translocation, triggering a superantigenic response, was tested.