Author:
Cuperlovic-Culf Miroslava,Cunningham Emma L.,Surendra Anu,Pan Xiaobei,Bennett Steffany A.L.,Jung Mijin,McGuiness Bernadette,Passmore Anthony Peter,McAuley Danny,Beverland David,Green Brian D.
Abstract
AbstractDelirium is an acute change in attention and cognition occurring in ~65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Significant concentration differences in several amino acids, acylcarnitines and polyamines were found in delirium-prone patients leading us to a hypothesis about the significance of monoamine oxidase B (MAOB) in predisposition to delirium. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein-protein docking analysis showed possibly strong binding of SARS-CoV-2 spike protein to MAOB resulting in a hypothesis that SARS-CoV-2 influences MAOB activity possibly lead to many observed neurological and platelet-based complications of SARS-CoV-2 infection. This proposition is possibly of significance for diagnosis, treatment and prevention of vulnerabilities causing delirium, dementias and severe COVID-19 response.
Publisher
Cold Spring Harbor Laboratory
Reference54 articles.
1. A Unique Presentation of Delirium in a Patient with Otherwise Asymptomatic COVID J19;Journal of the American Geriatrics Society,2020
2. COVID-19 update: Covid-19-associated coagulopathy;Journal of Thrombosis and Thrombolysis,2020
3. Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A
4. Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression;J Acquir Immune Defic Syndr,2015