King's College London

Researchers at the Institute of Psychology, Psychiatry & Neuroscience (IoPPN) at King’s College London have been given £14m to conduct a six-year research programme into the effects on children of maternal prenatal exposure to infection, with a focus on children conceived during the initial years of the COVID-19 pandemic.

The research programme, called Brain Health in Gen2020, will be split into two integrated parts: pre-clinical and clinical. This programme is being funded by Gabe Newell, co-founder of the philanthropic motorsports team The Heart of Racing, which raises funds and awareness to support youth health care.

The pre-clinical lab-based stage will build on previous work at King’s which identified an association between COVID-19 and haemorrhages in fetal brain tissue. Researchers will use state of the art laboratory techniques to examine how developing human neurons and fetal brain tissues respond to the virus, as well as to changes in the fetal-maternal immune system triggered by infection.

Dr Katie Long, lead researcher at the pre-clinical stage and Research Fellow in the Centre for Developmental Neurobiology at King’s IoPPN said, “The purpose of this stage of the research is to understand what the maternal immune response is to this infection in pregnant women and establish the potential impact that it has on fetal brain development.

“We have developed a lab-based model of fetal brain tissue that is as close to the developing human brain as possible – something that is only possible thanks to our longstanding collaboration with several world class fetal tissue banks.”

The team will then use computational modelling to understand how these cellular mechanisms may explain findings in the clinical stage.

Dr Long said, “One of the more problematic issues we face in human fetal brain research is how to translate our findings in the lab to the real world. It can take years for the things we observe in lab conditions to show in more clinical settings. By using computational modelling, we can be more proactive and predict how changes in cell behaviour can lead to changes in brain development.”

The clinical research stage will address a need identified by King’s scientists at the start of the pandemic: to conduct longitudinal research into fetal brain and outcomes of children who were ‘in the womb’ during the pandemic. We now understand that the immune system plays a crucial role in typical fetal brain development, therefore the way in which the maternal-fetal immune response is harnessed by an infection may influence the developing brain. This is complex, because every fetal-maternal pair is unique, with individual profiles of resilience and vulnerability.

Professor Grainne McAlonan, the clinical stage lead researcher, Clinical Professor of Translational Neuroscience and interim Director of the NIHR Maudsley Biomedical Research Centre at King’s IoPPN and South London and Maudsley NHS Foundation Trust said, “Early in the pandemic we identified a need to understand what, if anything, fetal exposure to maternal infection does to brain development. COVID-19 presented an opportunity, indeed a responsibility, to address this question. We therefore repurposed our existing studies of the developing brain (using MRI and in-depth developmental fetal assessments) to include fetuses and newborns whose mothers had COVID-19 in pregnancy. Dr Long’s subsequent study of fetal tissue has reinforced the importance of doing this work in living children.

“This generous funding will allow us to carry out in-depth analyses of this unique dataset and follow-up on these children as they enter primary education. It also means we can expand our original sample to capture the likely wide range of outcomes of children who were in utero during the pandemic, both in-depth and at population level. This is only possible because we can bring together our strengths in neuroscience and NHS infrastructure in the U.K.”

Professor Shitij Kapur, Vice-Chancellor & President of King’s College London said, “The Covid-19 pandemic and subsequent lockdowns represent a unique period in all of our lives. Yet, with the worst hopefully behind us, our attention must now turn to more long-term questions.

“This funding – the largest single donation for health research that King’s has ever received – speaks to the sheer power of philanthropy, and will allow our researchers to investigate the effects of Covid-19 on brain development from the very earliest stages. It is testament to the standard of their research that mean Dr Long and Professor McAlonan are able to explore this vitally important area of work.”

 

For more information, please contact Patrick O’Brien (Media Manager)