Among the many confusing symptoms in patients recovering from a COVID-19 infection are memory loss and learning difficulties. However, little is known about the mechanisms of cognitive impairments such as these, commonly called brain fog.
In a new study, researchers at the University of Illinois at Chicago identified a mechanism that causes neurological problems in mice infected with SARS-CoV-2, the virus behind COVID-19. The researchers also found a treatment that helped prevent these changes. Sarah Lutz, assistant professor of anatomy and cell biology in the School of Medicine, led the research, which was published in the journal Brain.
The team focused on the blood-brain barrier, which plays a role in other neurological diseases, such as multiple sclerosis. Normally, this barrier protects the brain from potentially harmful cells or molecules circulating in the bloodstream. But the researchers found that infected mice had leaky blood vessels in the blood-brain barrier and memory or learning problems.
To understand why, the researchers looked at blood vessels in the brains of infected mice to see which genes were most altered. They found a significant decrease in a signaling pathway called Wnt/beta-catenin, which helps maintain the health of the blood-brain barrier and protects the brain from damage.
With these results, the team explored whether a gene therapy that stimulates the Wnt/beta-catenin pathway could prevent brain damage in mice infected with SARS-CoV-2.
In fact, he did just that.
“They had fewer leaks in the blood-brain barrier and less infiltration of immune cells in the brain, which led to improvements in learning and memory,” Lutz said.
Because age is a risk factor for cognitive decline in humans with COVID-19, the team focused on older mice in their research. They specifically tracked mild infections in the mice. Mild, rather than severe, infections account for the majority of human COVID-19 cases today, thanks to the vaccine. However, even mild infections can cause cognitive impairment, Lutz said.
While research is a long way from establishing a therapy for humans to prevent cognitive declines following infection, this study is an important step on that path, Lutz said.
“Any time you can identify a molecular mechanism that contributes to a disease, you are learning about basic biology and what causes the disease in general,” he said. “This research suggests that improving the integrity of the blood-brain barrier may have benefits in preventing COVID-19 complications.”
An important lesson from the COVID-19 pandemic is that even mild infections can profoundly affect organs, including the brain, explained Dr. Jalees Rehman, Benjamin Goldberg Professor and head of the Department of Biochemistry and Molecular Genetics at UIC and co-author of the study.
“More research needs to be done on respiratory infections that can affect the brain,” Rehman said. “The good news is that by studying the molecular signals activated by the infection, as well as during subsequent inflammation when the immune system responds to the infection, new targeted therapies can be developed that prevent further damage to the brain and other organs.”
The other authors of the UIC study are Troy Trevino, Avital Fogel, Guliz Otkiran, Seshadri Niladhuri, Mark Sanborn, Jacob Class, Ali Almousawi and Justin Richner.