As COVID-19 continues to affect the health of millions around the world, investigation on SARS-CoV-2, a relatively new coronavirus variant, also continues on its functions within various organs. A recent study was able to help explain the increasing number of SARS-CoV-2 patients with neurological symptoms which include dizziness, muscle weakness, confusion, seizures, and more. Scientists revealed that SARS-CoV-2 may contaminate nerve cells, hindering blood flow in the central nervous system.
Scientists from Yale School of Medicine in New Haven, CT, recently revealed that SARS-CoV-2 can directly infect cells in the central nervous system (CNS), leading to tissue damage. SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE 2) receptors on the cell surface, causing lung tissue infection. One the virus enters the lung tissue, it can cause respiratory symptoms such as difficulty in breathing and lingering chest pain. Recent studies appear that the virus not only infects lung tissue, but can also infect cells in the central nervous system (CNS), which consists the brain and spinal cord.
The studies made by scientists from Yale School of Medicine extended to research on analyzing the mechanisms of nerve cell infection. The team used three different brain models human brain organoids, genetically engineered mice, and autopsies of patients who had died from COVID-19.
Human brain organoids
Scientists utilized 3D brain organoid models produced from stem cells of healthy individuals to study the potential of SARS-CoV-2 infecting the brain. In the study, the organoids showed accumulation of SARS-CoV-2 positive cells in specific brain regions, which proved the potential of SARS-CoV-2 can not only infect neurons but also can replicate.
When comparing genes of infected and uninfected cells of SARS-CoV-2, infected cells displayed intense metabolism which would allow the replication of the virus more efficiently and limiting the oxygen supply of neighboring cells. This discovery allowed the possibility of virus altering cell metabolism, creating an environment where infected cells would replicate while the uninfected neighboring cells would decline.
The model also indicated that ACE2 receptor also allowed the entering of virus to brain cells, in a similar way that happens in the lungs.
Luckily, antibodies were introduced that would block the protein, making the virus unable to bind to the protein, leading to decline of cell infection.
Genetically engineered mice
The researchers also implemented a mouse model to detect CNS infection. Mice was genetically modified to produce human ACE2 proteins to examine the infection in humans. The infected mice demonstrated high levels of infected nerve cells that associates with disruption of flow of oxygen to the brain.
When comparing effects of CNS and lung infection in mice, CNS infection showed high sufficiency to death, causing weight loss and death in the mice.
Autopsies of COVID-19 patients
Lastly, researchers studied the brains of patients who had died from COVID-19 who all experienced respiratory failure. The brains displayed tissue damage and cell death caused from lack of blood flow. The damage were similarly observed as well in the brain organoid and genetically engineered mice, who also showed oxygen deprivation.
More research associated with CNS in relation to COVID-19 is still imperative, but the study of mechanisms of CNS in relation to COVID-19 still have provided insight.