A case report describing the immune response of an infant with congenital heart disease and severe COVID-19

Danielle Wurzel; Melanie R Neeland; Jeremy Anderson; Yara-Natalie Abo; Lien Anh Ha Do; Celeste M Donato; Julie E Bines; Zheng Quan Toh; Rachel A Higgins; Sedi Jalali; Theresa Cole; Kanta Subbarao; Alissa McMinn; Kate Dohle; Gabrielle M Haeusler; Sarah McNab; Annette Alafaci; Isabella Overmars; Vanessa Clifford; Lai-Yang Lee; Andrew J Daley; Jim Buttery; Penelope A Bryant; David Burgner; Andrew Steer; Shidan Tosif; Igor E Konstantinov; Trevor Duke; Paul V Licciardi; Daniel G Pellicci; Nigel W Crawford

doi:10.1038/s43856-021-00047-7

A case report describing the immune response of an infant with congenital heart disease and severe COVID-19

Commun Med (Lond). 2021 Nov 15:1:47. doi: 10.1038/s43856-021-00047-7. eCollection 2021.

Authors

Danielle Wurzel^#^{1

2

3

4}, Melanie R Neeland^#^{1

2}, Jeremy Anderson^#¹, Yara-Natalie Abo^{1

2

3}, Lien Anh Ha Do^{1

2}, Celeste M Donato^{1

2}, Julie E Bines^{1

2

3}, Zheng Quan Toh^{1

2}, Rachel A Higgins¹, Sedi Jalali¹, Theresa Cole^{1

2

3}, Kanta Subbarao^{2

5}, Alissa McMinn¹, Kate Dohle¹, Gabrielle M Haeusler^{1

2

3}, Sarah McNab^{1

2

3}, Annette Alafaci¹, Isabella Overmars¹, Vanessa Clifford^{1

2

3}, Lai-Yang Lee^{1

2

3}, Andrew J Daley^{1

2

3}, Jim Buttery^{1

2

3

6}, Penelope A Bryant^{1

2

3}, David Burgner^{1

2

3}, Andrew Steer^{1

2

3}, Shidan Tosif^{1

2

3}, Igor E Konstantinov^{2

3

7}, Trevor Duke^{1

2

3}, Paul V Licciardi^{1

2}, Daniel G Pellicci^{1

2

8

7}, Nigel W Crawford^{1

2

3}

Affiliations

¹ Infection and Immunity, Murdoch Children's Research Institute, Melbourne, VIC Australia.
² Department of Paediatrics, University of Melbourne, Melbourne, VIC Australia.
³ Royal Children's Hospital, Melbourne, VIC Australia.
⁴ Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC Australia.
⁵ WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC Australia.
⁶ Monash Children's Hospital, Melbourne, VIC Australia.
⁷ Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, Murdoch Children's Research Institute, Melbourne, VIC Australia.
⁸ Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC Australia.

^# Contributed equally.

Abstract

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.

Keywords: Paediatric research; Viral infection.