Long-Covid and Post-Covid: Changes in the brain studied
Depositions can cause disorders of the nervous system
A study by the University of Veterinary Medicine Hannover (TiHo) Foundation, recently published in the journal “eBioMedicine – The Lancet”, suggests that the protein composition of neurons in the brain changes after a SARS-CoV-2 infection has been overcome.
In their investigations, the scientists discovered accumulations of misfolded and structurally altered proteins, which are also observed in Alzheimer’s and Parkinson’s patients. These deposits could cause disorders of the nervous system and possibly explain the concentration and memory problems reported in many Long Covid sufferers. In addition, the research team found an activation of microglial cells at the beginning of the infection, which were still present after the symptoms had subsided. The scientists examined the brains of Syrian golden hamsters that had been infected with SARS-CoV-2.
Strong activation of microglial cells in brain tissue
During the acute infection phase, the researchers were able to show that SARS-CoV-2 activated immune cells in the epithelium of the nasal cavity and in the olfactory bulb of the brain. “It is remarkable that the activation of microglial cells in the brain tissue, i.e. the local immune defence, was still present 14 days after the infection”, reports Prof. Dr. med. vet. Franziska Richter-Assencio from the Institute of Pharmacology, Toxicology and Pharmacy. When the infection had already subsided, the scientists discovered:inside misfolded alpha-synuclein proteins and structurally altered tau proteins that had accumulated in the neurons of the cerebral cortex.
These proteins are important in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. “The fact that not all brain regions were affected is an important finding that points to a selective sensitivity typical of neurodegenerative diseases”, Richter-Assencio explains.
Up to 67 percent of Covid 19 patients experience neurological symptoms during the acute infection. These may persist after the infection or reappear weeks later. These include neurological, neuropsychological and neuropsychiatric symptoms such as cognitive impairment, sleep disturbances, headaches, dizziness, depression, anxiety, gait disturbances and general fatigue. However, the pathogenesis of these symptoms remains unclear and, apart from rehabilitation, there are currently no effective treatments.
“Studies of biomarkers of neurodegenerative disease in plasma and brain integrity imaging in Long and post-Covid 19 patients, respectively, show results that are consistent with our observations. The diversity of symptoms clearly indicates the involvement of different brain regions,” explains Richter-Assencio. “Whether and how SARS-CoV-2 enters the brain is still unclear. We have not been able to detect the virus in the brain at any time in our studies, but there are also studies that have found small amounts of the virus in the brain. It would also be possible that the immune response to the virus alone, and associated signalling molecules such as cytokines, cause the observed changes.”
The researchers suggest that the accumulation of tau and alpha-synuclein proteins could be a cause of the long-lasting neurological symptoms. Richter-Assencio emphasises: “There is still a lot of research to be done. Whether the accumulation of the proteins in the neurons actually triggers progressive neurodegenerative processes and neurological symptoms must be shown in further studies. One thing is certain, however: if we understand the causes of the symptoms of long and post covid, targeted therapy approaches for those affected can be developed based on this. Alpha-synuclein and tau, if our suspicions are confirmed, could be important targets for such forms of therapy.”
Christopher Käufer, Cara S. Schreiber, Anna-Sophia Hartke, Ivo Denden, Stephanie Stanelle-Bertram, Sebastian Beck, Nancy Mounogou Kouassi, Georg Beythien, Kathrin Becker, Tom Schreiner, Berfin Schaumburg, Andreas Beineke, Wolfgang Baumgärtner, Gülsah Gabriel, Franziska Richter; Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model; eBioMedicine – The Lancet; 2022