Mechanisms Underlying SARS-CoV-2 Neuroinvasion Discovered

Henrietta Brewer
January 14, 2021

As a new, more infectious strain of SARS-CoV-2 spreads further from the United Kingdom and across the United States, the U.S. Food and Drug Administration (FDA) is advising that its impact on molecular tests will likely be low, with three approved tests now affected. Researchers have identified the spike glycoprotein as the most important surface protein of SARS-CoV-2, which can mediate the virus entry into human respiratory epithelial cells by interacting with cell surface receptor angiotensin-converting enzyme 2 (ACE2).

The model, published January 12 in Science, draws upon studies of the four common cold coronaviruses and SARS-CoV-1.

Notably, tests that rely on detection within multiple regions of a patient's genome may be less affected by genetic variation in the SARS-CoV-2 genome than those with a narrow focus on a single region. How fast this shift comes depends on how fast the virus spreads and what kind of immune response the SARS-CoV-2 vaccines induce.

The research suggests that endemic SARS-CoV-2 may become a disease of early childhood, where the first infection occurs between 3 and 5 years old, and the disease itself would be mild.

The researchers revealed that the virus was able to infect neurons in these organoids and use the neuronal cell machinery to replicate. The virus also appeared to facilitate its replication by boosting the metabolism of infected cells, while neighbouring, uninfected neurons died as their oxygen supply was reduced.

The Yale team determined that the ACE2 protein is, in fact, produced by neurons and that blocking this protein prevents the virus from human brain organoids.

Central nervous system infection was much more lethal in mice than infections limited to the lungs, they added.

"The FDA will continue to monitor SARS-CoV-2 genetic viral variants to ensure authorized tests continue to provide accurate results for patients", Dr. Stephen Hahn, FDA Commissioner, said. "First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons".

SARS-CoV-2 can also cause dramatic alterations in the brain's blood vessels that could potentially disrupt the organ's oxygen supply, the authors wrote. But despite the fact that slow vaccine rollouts mean the USA won't achieve herd immunity for months to come, a study published Tuesday in Science also suggests COVID-19 is "here to stay", The New York Times reports.

An image of a human brain organoid shows numerous dying cells (green) surrounding neurons (gray) that have been infected by SARS-CoV-2 (red).

"Our study clearly demonstrates that neurons can become a target of SARS-CoV-2 infection, with devastating consequences of localised ischemia in the brain and cell death", Associate Professor Kaya Bilguvar said. "Our results suggest that neurologic symptoms associated with COVID-19 may be related to these consequences and may help guide rational approaches to the treatment of COVID-19 patients with neuronal disorders".

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