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Spotlight on SARS-CoV-2 in the foetal brain


The role of the maternal immune system and the impact of viruses on foetal brain development has generated a significant amount of research interest in recent years with several studies linking adverse neurodevelopment to maternal viral infections. In 2019, the virus behind the ongoing COVID-19 pandemic, SARS-CoV-2, emerged and although research has improved our understanding of it somewhat, little is known about the long-term effects, including prenatal exposure, of the virus. 

In a landmark new study, out now in Brain, Massimo et al. report on the presence of SARS-CoV-2 in foetal brain tissue and associated observations. Using foetal cortical tissue samples collected by the Human Developmental Biology Resource, the Long lab observed haemorrhages in approximately 3% of samples, with the receipt of affected first and second trimester samples reflecting COVID-19 case rates at the time. In collaboration with the School of Cardiovascular Medicine and Sciences and colleagues in Italy and Edinburgh, Marco Massimo et al. examined the level of SARS-CoV-2 in the cortical tissue of both haemorrhagic samples and controls and found the virus in the choroid plexus and cortex of affected samples but not in controls. All haemorrhagic samples contained the virus but interestingly, two without notable pathology also contained SARS-CoV-2. 

The researchers next sought to identify how these haemorrhages may have come about and identified the blood vessels in the tissue. Massimo et al.’s data indicated a reduction in blood vessel integrity in the affected samples, suggesting that ‘leaky vessels’ had led to the appearance of the haemorrhages. In their final series of experiments, the researchers then explored the immune response in the tissue samples and found differences in the distribution of CD68 positive cells and a significant increase in monocytes in the haemorrhagic tissue, suggesting the presence of an immune response in these samples. 

This important publication from the Long lab offers striking initial insights into the effect of SARS-CoV-2 infection on the foetal brain. Massimo et al. report that SARS-CoV-2 was detected in all the samples presenting with haemorrhages examined, but whether these haemorrhages are a direct consequence of the infection or an indirect consequence of the maternal immune response to SARS-CoV-2 is not yet known. One important point to note is that it is not yet known if the observed haemorrhages will resolve with minimal consequences or whether they could have an impact on neurodevelopment, highlighting the urgent need for extensive further research and clinical monitoring in this area.