Some people who have had COVID-19 experience neurological symptoms such as headaches, loss of taste and smell, and exhaustion. A new study by researchers from Macquarie University in Sydney, the University of Queensland and the University of Helsinki, Finland, has shown that viruses like the one that causes COVID-19 can cause brain cells to fuse and malfunction. The findings may explain the “brain fog” and other neurological symptoms that some people experience after being infected with SARS-Cov-2.
How the virus works
It is well known that some viruses, including the severe acute respiratory syndrome 2 (SARS-CoV-2) coronavirus, which causes COVID-19, affect the brain and nervous system by infecting nerve cells (neurons). Some viruses do not kill host cells, but cause brain dysfunction. The mechanism by which they do this is clear to non-brain cells: viruses use special molecules called fusogens to fuse with cells and penetrate them. The fusogens hijack the cell’s mechanism to produce more viruses, which spread the virus – and more fusogens – into neighboring cells. Until now, it was unclear how fusogens affect brain cells.
Researchers from Macquarie University in Sydney collaborated with the University of Queensland and the University of Helsinki, Finland, to study the effects of fusogens on the brain. The study relied on brain organoids, artificially grown “mini-brains” that mimic the real thing. “We reprogram human stem cells into brain cells, including neurons, and let them assemble into mini-brains in a cup,” said Yazi Ke, co-author of the study.
Some organoids were infected with viral fusogens, including SARS-CoV-2, and compared with uninfected control organoids. They found that the virus causes fusion between neurons, between neurons and glia, and between glia. Glia are non-neuronal cells in the brain and spinal cord that help maintain and protect neurons.
“We found that COVID-19 causes neurons to undergo a process of cell fusion that has not been seen before,” said Massimo Hilliard, one of the study’s co-authors. “Once neurons are infected with SARS-CoV-2, spike protein S appears in the neurons, and the neurons do not die after fusion.”
The spike protein, or S protein, is one of the key biological characteristics of SARS-CoV-2. It is located on the outside of the virus, which allows it to enter host cells and cause infection.
Impact on health
Researchers say this fusion without cell death may explain the chronic neurological symptoms that some people experience after infection with COVID-19, such as headaches, “brain fog,” loss of taste and smell and exhaustion. “In the current understanding of what happens when the virus enters the brain, there are two outcomes – either cell death or inflammation,” said Ramon Martinez-Marmol, lead author of the study. “But we showed a third possible outcome — neuronal fusion.”
The study reveals a new mechanism for the neurological events that follow a viral infection, leading to a better understanding of the long-term effects of COVID-19 and possibly other neurological conditions. “This very comprehensive study can help us understand some of the mechanisms of this viral behavior,” said Lars Ittner, one of the study’s co-authors. “We’ve also started a research program in our lab to understand the effects of COVID infections on the brain and how it affects the progression, outcome and even onset of dementia.”