SARS-CoV-2 neurovirulence changes in different variants of concern
SARS-CoV-2 is the aetiological agent of COVID-19, a disease responsible for a world-wide pandemic and considerable mortality and morbidity. Like other coronaviruses, it has been previously linked with a neurological tropism, although the exact virological and cellular mechanisms underpinning these infections remain under-studied. Here we demonstrate that not only is SARS-CoV-2 neurovirulent, we show that it can specifically infect and replicate within neurons and astrocytes, but is non-infectious in microglial cells. We also observe significant differences in levels of infection, and neuronal response to infection, between different variants of concern (VOCs), illustrating that relatively small genetic changes can underpin major phenotypic differences in tropism and neurovirulence. These results have implications for both the ongoing study of SARS-CoV-2, as new variants continue to arise, and for improving our understanding of the link between viral phenotype and the observed short-term and chronic neurological impact on the human host, encompassed by Long COVID.
SARS-CoV-2 is the aetiological agent of COVID-19, a disease responsible for a world-wide pandemic and considerable mortality and morbidity. Like other coronaviruses, it has been previously linked with a neurological tropism, although the exact virological and cellular mechanisms underpinning these infections remain under-studied. Here we demonstrate that not only is SARS-CoV-2 neurovirulent, we show that it can specifically infect and replicate within neurons and astrocytes, but is non-infectious in microglial cells. We also observe significant differences in levels of infection, and neuronal response to infection, between different variants of concern (VOCs), illustrating that relatively small genetic changes can underpin major phenotypic differences in tropism and neurovirulence. These results have implications for both the ongoing study of SARS-CoV-2, as new variants continue to arise, and for improving our understanding of the link between viral phenotype and the observed short-term and chronic neurological impact on the human host, encompassed by Long COVID.
Centre for Human Genetics