Paediatrics (RCH) - Research Publications

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    A case report describing the immune response of an infant with congenital heart disease and severe COVID-19
    Wurzel, D ; Neeland, MR ; Anderson, J ; Abo, Y-N ; Do, LAH ; Donato, CM ; Bines, JE ; Toh, ZQ ; Higgins, RA ; Jalali, S ; Cole, T ; Subbarao, K ; McMinn, A ; Dohle, K ; Haeusler, GM ; McNab, S ; Alafaci, A ; Overmars, I ; Clifford, V ; Lee, L-Y ; Daley, AJ ; Buttery, J ; Bryant, PA ; Burgner, D ; Steer, A ; Tosif, S ; Konstantinov, IE ; Duke, T ; Licciardi, PV ; Pellicci, DG ; Crawford, NW (SPRINGERNATURE, 2021-11-15)
    BACKGROUND: Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. METHODS: We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. RESULTS: Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. CONCLUSIONS: These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.
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    Immune Responses in an Infant with Congenital Heart Disease and Severe COVID-19 
    Licciardi, P ; Wurzel, D ; Neeland, M ; Anderson, J ; Abo, Y-N ; Do, LAH ; Donato, C ; Bines, J ; Toh, ZQ ; Higgins, R ; Jalali, S ; Cole, T ; Subbarao, K ; McMinn, A ; Dohle, K ; Haeusler, G ; McNab, S ; Alafaci, A ; Overmars, I ; Clifford, V ; Lee, L-Y ; Daly, A ; Buttery, J ; Bryant, P ; Burgner, D ; Steer, A ; Tosif, S ; Konstantinov, I ; Duke, T ; Pellicci, D ; Crawford, N ( 2021)
    Children have lower hospitalisation and mortality rates for coronavirus disease-2019 (COVID-19) than adults; however, younger children (<4 years of age) 1 may develop more severe disease than older children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterized. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19. Systemic cellular and cytokine profiling showed initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8+ T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4+T (but not CD8+T) cells occurred over time, with predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Significant in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory.