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COVID-19 in children: a prospective study investigating host response to SARS-CoV-2. Cathal Roarty (24169272) PUREID: 617911667 MIS-C Proteomics Infection paediatrics Immunology Biomarker COVID-19 Bacterial infections Clinical trial Fever This thesis explores the clinical features, immunology, and outcomes of Multisystem Inflammatory Syndrome in Children (MIS-C), a severe post COVID-19 condition identified during the early waves of the pandemic. 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. Although markers of intestinal permeability were elevated in MIS-C, they were also raised in other febrile conditions, and the hypothesis of spike protein superantigenicity was not supported.In summary, this thesis provides new insights into the clinical features, proteomic profile, and outcomes of MIS-C, identifies candidate diagnostic biomarkers, and challenges current hypotheses regarding the condition’s pathogenesis.<br><br><i>Thesis embargoed until 31st December 2029 </i><br> 2026-10-01T16:31:01Z Text Thesis 10.17034/32640456.v1 https://figshare.com/articles/thesis/COVID-19_in_children_a_prospective_study_investigating_host_response_to_SARS-CoV-2_/32640456 All Rights Reserved Open Access after 2029-12-31