Objective: This study can provide an important insight for identification and prediction of long term neurological sequelae of SARS-CoV-2 infection and proper clinical management the survivors.

Background: Parkinson’s disease (PD) is closely linked to immune responses induced by microbial infections such as Herpes virus, Helicobacter pylori, hepatitis C virus, or pneumococcus. However, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the onset and progression of PD is yet to be investigated. At the tail end of the current COVID-19 pandemic, it is critical to predict and prepare for the biologically possible neurological sequelae of SARS-CoV-2 infection.

Method: We differentiated human embryonic stem cells to dopaminergic (DA) neurons, which was subsequently infected with SARS-CoV-2.

Results: SARS-CoV-2, in vitro, increased pre-formed fibril (PFF)-mediated cytotoxicity on DA neuron but also elevated susceptibility to PFF-induced PD-like pathology. Reflecting this phenotype, RNA sequencing of SARS-CoV-2 infected DA neurons demonstrated changes in expressions of signalling molecules in apoptosis, autophagy, oxidative stress, and mitochondrial function. Next, we found that SARS-CoV-2 was successfully detected in the brains of human angiotensin-converting enzyme 2 transgenic (hACE2 Tg) mice that were intra-nasally infected with SARS-CoV-2. And SARS-CoV-2 infection further amplified inflammatory response in microglia and astrocytes in comparison to PFF treatment alone, which was, to our surprise, maintained for 60 days even after complete clearance SARS-CoV-2 from the brain. Furthermore, while SARS-CoV-2 infection alone was unable to exert cytotoxic effect on DA neurons, it increased susceptibility of PFF-induced DA neuronal death.

Conclusion: Based on these results, we suggest a previously unappreciated paradigm that neuroinflammation triggered by SARS-CoV-2 infection persists in the brain after viral clearance and can increase susceptibility to PD a long-term sequela.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/sars-cov-2-infection-exacerbates-the-cellular-pathology-in-parkinsons-disease-progression/