A study of the clinical characteristics and immunopathology of SARS-CoV-2 associated diseases in children

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic presented a remarkable epidemiological trend, with low rates of severe paediatric cases and an age-dependent increase in disease severity, raising questions about underlying mechanisms. A small proportion of children developed a severe inflammatory illness several weeks after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This syndrome, now called Multisystem Inflammatory Syndrome in Children (MIS-C) is characterised by fever, rash, and conjunctivitis, and can rapidly progress to shock and multiorgan failure. The overlapping features of MIS-C with other conditions, including Kawasaki Disease and sepsis, posed additional challenges. Following the introduction of COVID-19 vaccines there were reports of increased rates of myocarditis in young adults. The evolving diseases associated with SARS-CoV-2 raised many questions regarding the immunopathogenesis of these diverse syndromes, diagnostic approaches, and treatment strategies.

I aimed to explore and understand the clinical characteristics and immunopathology of SARS-CoV-2 associated diseases in children by using a multidisciplinary approach including: descriptive analyses of large clinical datasets, development of diagnostic and severity scores, antibody profiling and mechanistic studies investigating the role of antibodies and T cells.

Key findings include: • Age-related differences in COVID-19 severity are not driven by antibody dependent enhancement. • A clinical diagnostic score can accurately differentiate MIS-C from other conditions. • Utility of SARS-CoV-2 serology testing for MIS-C diagnosis diminishes over time. • A clinical and laboratory marker-based severity score can identify MIS-C patients at risk of severe disease. • The cardiac pathology in MIS-C and COVID-19 vaccine-induced myocarditis is unlikely to be antibody driven. • Acute MIS-C exhibit reduced T cell response to antigen stimulation, suggesting transient T cell exhaustion.

My research contributes to the understanding of the clinical and immunological aspects of SARS-COV-2 associated diseases in children and the findings have significant implications for vaccine development, clinical management and provide critical insights that can guide further research.