Investigating the impact of COVID-19 on Parkinson's disease

Neuropathology of COVID-19 is characterized by a peculiar neuroimmunological activation with astro/microgliosis and increased inflammatory signaling. SARS-CoV-2 has an affinity for the basal ganglia/brainstem and has been shown to affect the nervous system, causing neurological symptoms. Although there have been single case reports of COVID-19 patients having developed parkinsonism within weeks of contracting the virus, there is currently only speculative evidence for a link between COVID-19 and PD. Since this potential link will only become obvious in the coming years or decades, it is pertinent to investigate if and how COVID-19 impacts PD. We hypothesize that studying brains of COVID-19 patients, COVID-19 patients with concomitant PD as compared to PD patients and controls will inform us on a potential link and will unravel pathways active in COVID-19-modulated PD with biomarker relevance. We hypothesize that neuroimmunological activation in COVID-19 lead to accelerated neurodegeneration. This proposal aims to compare the neuropathology and perturbed biological pathways of PD patients and controls with and without COVID-19 to understand these mechanisms. Specifically, we will investigate 1) neuroimmune activation and protein folding/deposition and clearance pathways across different regions of the brain (cortex, striatum, substantia nigra, cerebellum) and 2) differentially expressed genes in frontal cortex and midbrain of the above-mentioned groups by 2a) global RNA transcriptomics and 2b) single-cell RNA sequencing to map disease-specific patterns on a single-cell level. Lastly, we will 3) integrate all targeted and global approaches to identify biological pathways active in COVID-19/PD and COVID-19 and assess biomarker potential of obtained marker profiles in living PD patients post COVID-19 to predict PD outcome. By thoroughly exploring whether there is a relationship between COVID-19 and PD, this proposal will inform us on the risk SARS-CoV-2 infections pose the development or worsening of.