Researchers discover pathways to severe COVID-19 in children

Researchers have discovered the blood clotting and immune protein pathways that are activated in severe cases of COVID-19 in children, paving the way for earlier diagnosis and more targeted treatments.

The study led by the Murdoch Children's Research Institute (MCRI) and the University of Melbourne and published in Nature Communications, has identified disease mechanisms in children with COVID-19 who present with multisystem inflammatory syndrome, where different body parts can become inflamed including the heart, lungs, and brain and acute respiratory distress syndrome, a type of lung disease.

MCRI researcher and University of Melbourne PhD student Conor McCafferty said the main triggers for severe COVID-19 in children were blood clotting and how proteins in the immune system reacted to the virus.

"Children are in general less susceptible to COVID-19 and present with milder symptoms, but it remained unclear what caused some to develop very severe disease," he said.

"Our research was the first to uncover the specific blood clotting and immune protein pathways impacted in children with COVID-19 who developed serious symptoms."

For the study, blood samples from 20 healthy children were collected at The Royal Children's Hospital and samples from 33 SARS-CoV-2 infected children with multisystem inflammatory syndrome or acute respiratory distress syndrome were collected from the Hôpital Necker-Enfants Malades, Greater Paris University Hospitals.

Professor Damien Bonnet, from the Hôpital Necker-Enfants Malades, Greater Paris University Hospitals, said collecting samples to further describe the mechanisms of these syndromes and establishing worldwide collaborations were considered key issues to improve treatment and outcomes.

The research found 85 and 52 proteins were specific to multisystem inflammatory syndrome and acute respiratory distress syndrome, respectively. Both syndromes are major potential outcomes of severe COVID-19.

Mr McCafferty said the discoveries were possible due to proteomics, an experimental approach that allowed the researchers to investigate almost 500 proteins circulating in the blood at once.

Data shows 1.7 per cent of reported paediatric hospitalised cases of COVID-19 included admission to the Intensive Care Unit. There have been 50 reported cases of multisystem inflammatory syndrome in Australia since the start of the pandemic up until February this year. Children with COVID-19 who present with multisystem inflammatory syndrome also show similar clinical features to Kawasaki disease and toxic shock syndrome such as fever, abdominal pain, vomiting, skin rash and conjunctivitis, making it difficult to quickly diagnose patients.

MCRI Professor Vera Ignjatovic said the results provided an understanding of the processes that underlie severe COVID-19 in children, which would help in the development of diagnostic tests for early identification of children at risk, as well as therapeutic targets to improve the outcomes for those with severe cases.

"Knowing the mechanisms associated with severe COVID-19 in children and how the blood clotting and immune systems in children react to the virus will help diagnose and detect acute COVID-19 cases and allow us to develop targeted treatment," she said. 

Researchers from the Australian Proteome Analysis Facility in Sydney also contributed to the study.

Publication: 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. 'Pathophysiological pathway differences in children who present with COVID-19 ARDS compared to COVID-19 induced MIS-C,' Nature Communications. DOI: 10.1038/s41467-022-29951-9

Available for interview:

Conor McCafferty, MCRI researcher and University of Melbourne PhD student

Professor Vera Ignjatovic, MCRI Co-Group Leader, Haematology and University of Melbourne Honorary Professor

Professor Paul Monagle, University of Melbourne Paediatric Haematologist and MCRI Co-Group Leader, Haematology

Professor Damien Bonnet, Head of the Department of Pediatric Cardiology, Hôpital Necker-Enfants Malades, Greater Paris University Hospitals

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About MCRI

The Murdoch Children's Research Institute (MCRI) is the largest child health research institute in Australia committed to making discoveries and developing treatments to improve child and adolescent health in Australia and around the world. They are pioneering new treatments, trialling better vaccines, and improving ways of diagnosing and helping sick babies, children and adolescents. It is one of the only research institutes in Australia to offer genetic testing to find answers for families of children with previously undiagnosed conditions.

Funding 

The study was funded by The Royal Children's Hospital Foundation. Aspects of this work was conducted at the Australian Proteome Analysis Facility and supported by the Australian Governments National Collaborative Research Infrastructure Scheme (NCRIS).