Abstract - 5
Neuro-COVID-19: a meta-analysis of COVID-19-induced neuroinflammation and its implications
Sulie L. Chang 1,2* , Wenfei Huang 1,2 , Angelo Montero 1,2 , Muhammed Bishir 3 , and Saravana Babu
Chidambaram 3
1 Institute of Neuroimmune Pharmacology and 2 Department of Biological Sciences, New Jersey, USA; 3 Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, India
*Corresponding author: sulie.chang@shu.edu
As the COVID-19 pandemic continues to impact the world, it has become clear that the disease caused by SARS-CoV-2 is not only a respiratory illness. In addition to respiratory symptoms and multiorgan failure, neurological symptoms have also been observed in clinics. Moreover, neurological manifestations, in the form of cognitive deficits, have persisted even in the recovered patients. We therefore hypothesize that COVID-19 causes neuroinflammation, which could in turn contribute to the formation of the neurological symptoms. In the present meta-analysis study, we identified and analyzed the molecules affected by COVID-19 using the bioinformatics tool QIAGEN Ingenuity Pathway Analysis (IPA) to demonstrate possible pathogenic mechanism underlying COVID-19-induced neuroinflammation. Using the Core Analysis and My Pathway tools of IPA, our data demonstrated a strong association between the
molecules affected by COVID-19 and the canonical pathway of Neuroinflammation Signaling Pathway, as well as three neurological diseases associated with inflammatory response (Inflammation of central nervous system, Encephalitis and Experimental autoimmune encephalomyelitis). Lipopolysaccharide
(LPS) and Interferon gamma (IFNG) were identified to be the top two upstream regulators that may account for the change of the molecules affected by COVID-19. Regulatory networking of LPS and IFGN counteracted with each other. In line with the fact that SARS-CoV-2 binds and downregulates angiotensin-converting enzyme 2 membrane receptor (mACE2), our data also demonstrated that downregulation of mACE2 activated the Neuroinflammation Signaling Pathway, through activation of Nuclear factor kappa B (NFκB)-induced elevation of cytokines and inhibition of IFNγ-induced antiviral response via direct interaction and indirect effects. Together, our meta-analysis has suggested that COVID-19 causes neuroinflammation leading to neurological pathogenesis, via modulating the major inflammatory pathways like NF-κB, IFN, Jak-STAT that is observed in the disease.