Meta-Analysis of the Mechanisms Underlying COVID-19 Modulation of Parkinson’s Disease (preprint)

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Network Meta-Analysis on the Mechanisms underlying Type 2 Diabetes Augmentation of COVID-19 Pathologies (preprint)

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. SARS-CoV-2 virus is internalized by surface receptors, e.g., angiotensin-converting enzyme-2 (ACE2). Clinical reports suggest that non-insulin dependent diabetes mellitus (DM-II) may enhance COVID-19. This study investigated how DM-II augments COVID-19 complications through molecular interactions with cytokines/chemokines, using QIAGEN Ingenuity Pathway Analysis (IPA) and CLC Genomics Workbench 22 (CLCG-22). RNA-sequencing of islet β-cell genomes through CLCG-22 (SRA SRP287500) were analyzed to identify differential expression of islet β-cell genes (Iβ-CG). IPA’s QIAGEN Knowledge Base (QKB) was also used to retrieve 88 total molecules shared between DM-II and SARS-CoV-2 infection to characterize and identify Iβ-CG, due to close association with DM-II. Molecules directly associated with ACE2 and cytokines/chemokines were also identified for their association with SARS-CoV-2 infection. Using IPA, 3 Iβ-CG in common with both diseases, SCL2A2, PPARγ, and CPLX8, were downregulated by DM-II. Their downregulation occurred due to increased activity of cytokines/chemokines and ACE2. Collectively, this network meta-analysis demonstrated that interaction of SARS-CoV-2 with ACE2 could primarily induce endothelial cell dysfunction. Identification of common molecules and signaling pathways between DM-II and SARS-CoV-2 infection in this study may lead to further discovery of therapeutic measures to simultaneously combat both diseases.