Thread by @vipintukur

Experts have discovered a mutation in SARS-CoV-2 that plays a key role in its ability to infect brain. This may help in understanding neurological symptoms & mystery of "long COVID," & could one day even lead to specific treatments to protect & clear the virus from brain 1/

Researchers discovered a series of mutations in the SARS-CoV-2 spike protein that enhanced the virus's ability to infect the brains of mice. 2/

They assessed SARS-CoV-2 evolution in the lung versus CNS of infected mice. Higher levels of viral divergence were observed in the CNS than the lung after intranasal challenge with a high frequency of mutations in the spike furin cleavage site (FCS). 3/

Looking at the genomes of viruses found in the brain compared to the lung, the researchers found that viruses with a specific deletion in spike (Furin Cleavage Site) were much better at infecting the brains of these animals. 4/

In this study, researchers infected mice with SARS-CoV-2 and sequenced the genomes of viruses that replicated in the brain versus the lung. In the lung, the spike protein looked very similar to the virus used to infect the mice. 5/

In the brain, however, most viruses had a deletion or mutation in a critical region of spike, i.e. FCS that dictates how it enters a cell. When viruses with this deletion were used to directly infect the brains of mice, it was largely repaired when it traveled to the lungs 6/

In order for the virus to traffic from the lung to the brain, it required changes in the spike protein that are already known to dictate how the virus gets into different types of cells. 7/

Researchers think this region of spike (FCS) is a critical regulator of whether or not the virus gets into the brain, and it could have large implications for the treatment and management of neurological symptoms reported by COVID-19 patients. 8/

It's still not known if #longCOVID is caused by direct infection of cells in the brain or due to some adverse immune response that persists beyond the infection. 9/

If it is caused by infection of cells in the central nervous system, this study suggests there may be specific treatments that could work better than others in clearing the virus from this compartment. 10/10

nature.com/articles/s4156…