ABSTRACT
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.
Subject(s)
Coronavirus Infections , Severe Acute Respiratory Syndrome , Inflammation , Parkinson Disease , COVID-19 , Neurodegenerative DiseasesABSTRACT
Objective: To quantify overall trends in patients treated for mental health disorders and adverse events, including via tele-mental health (TMH) and psychopharmacology during pandemic-related health care transformation.Methods: This longitudinal observational study analyzes veterans receiving mental health treatment at a Veterans Health Administration (VHA) facility from January 1, 2017 to June 16, 2020. Observed and expected patient care for on-going and new treatment of depression, posttraumatic stress, substance use disorder, severe mental illness diagnoses, overdose, and suicide attempts, and psychotropic prescriptions for antidepressant, antipsychotic, benzodiazepine, opioid, and mood stabilizing medications are depicted. Percent change between actual and expected counts in the early months of the COVID pandemic (March 18-May 5, 2020) are computed.Results: Decreases in counts of patients receiving care for mental health treatment during early pandemic response ranged from 7% to 20% for on-going treatment, and 28 to 37% for new treatment. TMH rapidly expanded across VHA, becoming the primary means by which encounters were delivered. The number of patients receiving on-going care for suicide attempts were stable and for overdoses, decreased 17%, while patients initiating care declined by 30% and 38%, respectively. Weekly prescriptions and medication on-hand for psychotropics ranged from a 2% decline to 4% increase. Prescribing to new patients declined 21 to 50%.Conclusions: VHA needs to expand outreach and continue to utilize TMH to maintain care continuity and initiate care for existing and new patients. This knowledge is useful for healthcare systems in developing strategies for COVID-19 and future large-scale outbreaks, epidemic, and disasters.Funding: These studies were supported through funding for medical operations by the Department of Veterans Affairs through the VA Office of Mental Health and Suicide Prevention.Declaration of Interests: Matt Boden is a consultant for the Beneath the Surface Foundation. None of the other authors have any potential conflicts of interest to disclose.Ethics Approval Statement: Data used in this study is captured in electronic medical records as part of routine clinical care and is utilized for the purpose of ongoing program evaluation. Thus, no institutional review board review was required for the study.