Pathophysiological pathway differences in children who present with COVID-19 ARDS compared to COVID -19 induced MIS-C

Conor McCafferty, Tengyi Cai, Delphine Borgel, Dominique Lasne, Sylvain Renolleau, Meryl Vedrenne-Cloquet, Damien Bonnet, Jemma Wu, Thiri Zaw, Atul Bhatnagar, Xiaomin Song, Suelyn Van Den Helm, Natasha Letunica, Chantal Attard, Vasiliki Karlaftis, Slavica Praporski, Vera Ignjatovic () and Paul Monagle
Additional contact information
Conor McCafferty: Haematology Research, Murdoch Children’s Research Institute
Tengyi Cai: Haematology Research, Murdoch Children’s Research Institute
Delphine Borgel: Necker Hospital, AP-HP
Dominique Lasne: Necker Hospital, AP-HP
Sylvain Renolleau: Necker Hospital AP-HP
Meryl Vedrenne-Cloquet: Necker Hospital AP-HP
Damien Bonnet: M3C-Necker, Congenital and Pediatric Cardiology, Necker Hospital, AP-HP
Jemma Wu: Australian Proteome Analysis Facility
Thiri Zaw: Australian Proteome Analysis Facility
Atul Bhatnagar: Australian Proteome Analysis Facility
Xiaomin Song: Australian Proteome Analysis Facility
Suelyn Van Den Helm: Haematology Research, Murdoch Children’s Research Institute
Natasha Letunica: Haematology Research, Murdoch Children’s Research Institute
Chantal Attard: Haematology Research, Murdoch Children’s Research Institute
Vasiliki Karlaftis: Haematology Research, Murdoch Children’s Research Institute
Slavica Praporski: Haematology Research, Murdoch Children’s Research Institute
Vera Ignjatovic: Haematology Research, Murdoch Children’s Research Institute
Paul Monagle: Haematology Research, Murdoch Children’s Research Institute

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract COVID-19 has infected more than 275 million worldwide (at the beginning of 2022). Children appear less susceptible to COVID-19 and present with milder symptoms. Cases of children with COVID-19 developing clinical features of Kawasaki-disease have been described. Here we utilise Mass Spectrometry proteomics to determine the plasma proteins expressed in healthy children pre-pandemic, children with multisystem inflammatory syndrome (MIS-C) and children with COVID-19 induced ARDS. Pathway analyses were performed to determine the affected pathways. 76 proteins are differentially expressed across the groups, with 85 and 52 proteins specific to MIS-C and COVID-19 ARDS, respectively. Complement and coagulation activation are implicated in these clinical phenotypes, however there was significant contribution of FcGR and BCR activation in MIS-C and scavenging of haem and retinoid metabolism in COVID-19 ARDS. We show global proteomic differences in MIS-C and COVID-ARDS, although both show complement and coagulation dysregulation. The results contribute to our understanding of MIS-C and COVID-19 ARDS in children.

Date: 2022
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DOI: 10.1038/s41467-022-29951-9

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