A study conducted by City of Hope, an independent biomedical research and treatment center, has discovered the gene ApoE4, which increases the risk for Alzheimer’s disease, can also increase the susceptibility to and severity of an infection with the coronavirus disease 2019 (COVID-19). Results from the research were published in the journal Cell Stem Cell.
The study was initially started due to an interest in assessing how a COVID-19 infection impacts the brain. Because the disease presents symptoms like a loss of smell and taste, it was believed that the virus had underlying neurological effects.
The investigators employed pluripotent stem cells (iPSCs), a type that easily becomes any kind of cell, to create neurons and helper cells called astrocytes. They infected both cells with the SARS-CoV-2 virus and found that they were susceptible to the disease. They then created 3D brain tissue models called organoids, one with and one without the astrocytes, also infecting them with COVID-19 and discovered that the astrocytes actually amplified the infection.
Additionally, the team used reprogrammed iPSCs to generate neurons from the cells of an Alzheimer’s patient containing ApoE4. Modifying the iPSCs with a gene editing tool so that they contained ApoE3, a neutral gene type, they created more astrocytes and neurons.
Findings showed that in comparison to the ApoE3 cells, the ApoE4 cells showed a significantly higher susceptibility to COVID-19 and had more damage inflicted on their neurons and astrocytes.
"Our study provides a causal link between the Alzheimer's disease risk factor ApoE4 and COVID-19 and explains why some (e.g., ApoE4 carriers) but not all COVID-19 patients exhibit neurological manifestations," Yanhong Shi, director of the Division of Stem Cell Biology at City of Hope and co-corresponding author said. "Understanding how risk factors for neurodegenerative diseases impact COVID-19 susceptibility and severity will help us to better cope with COVID-19 and its potential long-term effects in different patient populations."
The next step in the process will be to continue studying the impact that COVID-19 has on the brain to further understand the potential long-term neurological impacts like severe headaches experienced by some months after the initial infection.
"COVID-19 is a complex disease, and we are beginning to understand the risk factors involved in the manifestation of the severe form of the disease" said Vaithilingaraja Arumugaswami, a co-corresponding author said. "Our cell-based study provides a possible explanation as to why individuals with Alzheimer's' disease are at increased risk of developing more severe COVID-19 symptoms."