Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles are related to Neurodegenerative Diseases and COVID-19.
Title: The blood-brain barrier in health, neurological diseases, and COVID-19
Authors: Jianan Chen, Rongbang Tan, Yuqian Mo, Jingjing Zhang
The blood-brain barrier (BBB) is a protective interface between the central nervous system (CNS) and the circulating blood, and is critical in controlling the movement of ions, molecules and cells to maintain CNS homeostasis. The disruption of BBB is a key event responsible for the pathology in a number of neurological diseases and has also been shown to be involved in the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infections recently. In this review, we discuss the cellular and molecular components orchestrating BBB formation and function maintenance across species. How this barrier can be modulated for efficient drug delivery into the brain, and how BBB breakdown participates in neurological diseases are discussed. Finally, we highlight the recent work identifying the possible mechanisms by which SARS-CoV-2 invades CNS by crossing BBB in Corona Virus Disease 2019 (COVID-19) patients.
Access this article: https://doi.org/10.1016/j.fmre.2022.03.003
Title: Inflammation at the crossroads of COVID-19, cognitive deficits and depression
Authors: Natalia M. Lyra e Silva, Fernanda G.Q. Barros-Aragão, Fernanda G. De Felice, Sergio T. Ferreira
●COVID-19 is frequently associated with acute or persistent neurological impacts.
●COVID-19 survivors may be at increased risk for cognitive and mood disorders.
●Dementia and neuropsychiatric disorders appear to be risk factors for COVID-19 complications.
●Inflammation links COVID-19, Alzheimer's disease and depression.
Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain are being actively investigated. Due to the heterogeneous manifestations of neurological outcomes, it is possible that different mechanisms operate following SARS-CoV-2 infection, which may include direct brain infection by SARS-CoV-2, mechanisms resulting from hyperinflammatory systemic disease, or a combination of both. Inflammation is a core feature of COVID-19, and both central and systemic inflammation are known to lead to acute and persistent neurological alterations in other diseases. Here, we review evidence indicating that COVID-19 is associated with neuroinflammation, along with blood-brain barrier dysfunction. Similar neuroinflammatory signatures have been associated with Alzheimer's disease and major depressive disorder. Current evidence demonstrates that patients with pre-existing cognitive and neuropsychiatric deficits show worse outcomes upon infection by SARS-CoV-2 and, conversely, COVID-19 survivors may be at increased risk of developing dementia and mood disorders. Considering the high prevalence of COVID-19 patients that recovered from infection in the world and the alarming projections for the prevalence of dementia and depression, investigation of possible molecular similarities between those diseases may shed light on mechanisms leading to long-term neurological abnormalities in COVID-19 survivors.
Access this article: https://doi.org/10.1016/j.neuropharm.2022.109023
Title: COVID-19 and neurological sequelae: Vitamin D as a possible neuroprotective and/or neuroreparative agent
Authors: Sebastián García Menéndez, Virna Margarita Martín Giménez, Michael F. Holick, Francisco J. Barrantes, Walter Manucha
SARS-CoV-2, the etiological agent of the current COVID-19 pandemic, belongs to a broad family of coronaviruses that also affect humans. SARS-CoV-2 infection usually leads to bilateral atypical pneumonia with significant impairment of respiratory function. However, the infectious capacity of SARS-CoV-2 is not limited to the respiratory system, but may also affect other vital organs such as the brain. The central nervous system is vulnerable to cell damage via direct invasion or indirect virus-related effects leading to a neuroinflammatory response, processes possibly associated with a decrease in the activity of angiotensin II converting enzyme (ACE2), the canonical cell-surface receptor for SARS-CoV-2. This enzyme regulates neuroprotective and neuroimmunomodulatory functions and can neutralize both inflammation and oxidative stress generated at the cellular level. Furthermore, there is evidence of an association between vitamin D deficiency and predisposition to the development of severe forms of COVID-19, with its possible neurological and neuropsychiatric sequelae: vitamin D has the ability to down-modulate the effects of neuroinflammatory cytokines, among other anti-inflammatory/immunomodulatory effects, thus attenuating harmful consequences of COVID-19. This review critically analyzes current evidence supporting the notion that vitamin D may act as a neuroprotective and neuroreparative agent against the neurological sequelae of COVID-19.
Access this article: https://doi.org/10.1016/j.lfs.2022.120464
Title: COVID-19 infection and neurodegeneration: Computational evidence for interactions between the SARS-CoV-2 spike protein and monoamine oxidase enzymes
Authors: Lucija Hok, Hrvoje Rimac, Janez Mavri, Robert Vianello
●WT and the South African SARS‐CoV‐2 variant show comparable ACE2 and MAO affinities.
●Identified MAO/spike protein complexes modify MAO affinity for its neurotransmitters.
●Such changes impact metabolic clearance of brain amines and misbalance their level.
●This links MAO interference with neurological illnesses following COVID‐19 infection.
●More contagious SA variant gives larger MAO disturbances, which should not be ignored.
Although COVID-19 has been primarily associated with pneumonia, recent data show that its causative agent, the SARS-CoV-2 coronavirus, can infect many vital organs beyond the lungs, including the heart, kidneys and the brain. The literature agrees that COVID-19 is likely to have long-term mental health effects on infected individuals, which signifies a need to understand the role of the virus in the pathophysiology of brain disorders that is currently unknown and widely debated. Our docking and molecular dynamics simulations show that the affinity of the spike protein from the wild type (WT) and the South African B.1.351 (SA) variant towards MAO enzymes is comparable to that for its ACE2 receptor. This allows for the WT/SA⋅MAO complex formation, which changes MAO affinities for their neurotransmitter substrates, thereby impacting their metabolic conversion and misbalancing their levels. Knowing that this fine regulation is strongly linked with the etiology of various brain pathologies, these results are the first to highlight the possibility that the interference with the brain MAO catalytic activity is responsible for the increased neurodegenerative illnesses following a COVID-19 infection, thus placing a neurobiological link between these two conditions in the spotlight. Since the obtained insight suggests that a more contagious SA variant causes even larger disturbances, and with new and more problematic strains likely emerging in the near future, we firmly advise that the presented prospect of the SARS-CoV-2 induced neurological complications should not be ignored, but rather requires further clinical investigations to achieve an early diagnosis and timely therapeutic interventions.
Access this article: https://doi.org/10.1016/j.csbj.2022.02.020
Title: Post COVID-19 neurological complications; a meta-analysis
Authors: Jaafar Omer Ahmed, Shwan Abdubakr Ahmad, Marwan Nasih Hassan, Fahmi H. Kakamad, Rawezh Q. Salih, Berwn A. Abdulla, Fattah Hama Rahim Fattah, Shvan H. Mohammed, Razhan K. Ali, Abdulwahid M. Salih
Type: Systematic Review / Meta-analysis
●SARS-CoV-2 most commonly associates with pneumonia.
●However, new studies have indicated that many other organ systems can be involved.
●Also various neurological sequelae in COVID-19 individuals have been identified.
●The specific relationship between the infection and neurological disorders remains unknown.
●In this study, metadata were discussed regarding post COVID-19 neurological complications.
Despite numerous studies regarding neurological manifestations and complications of COVID-19, only a few cases of neurological consequences following complete recovery from SARS-CoV-2 infection have been described.
The current study aims to present a quantitative meta-analysis of published studies regarding the post-infectious neurological complications of COVID-19.
The Web of Science, PubMed, MEDLINE on OVID, and Google scholar were searched for English-language researches published after January 1, 2020.
The review of the literature revealed 60 cases - of which 40 (66.7%) cases were male, and 18 (30%) were female. The average age was 44.95 years. Overall, 17 (28.3%) patients had comorbid conditions. Twenty-four (40%) patients were hospitalized during an active COVID-19 infection. The average interval from the COVID-19 infection to the onset of neurological sequelae was 33.2 days. Guillain-Barre syndrome was the most commonly reported neurological condition (15, 25%).
Despite recovery from acute infection, the pandemic highlights the significance of ongoing, comprehensive follow-up of all COVID-19 patients - even those initially were believed to be asymptomatic.
Access this article: https://doi.org/10.1016/j.cell.2022.02.026