Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
1.
Indian J Pathol Microbiol ; 65(Supplement): S146-S152, 2022 May.
Article in English | MEDLINE | ID: covidwho-1847488

ABSTRACT

The COVID-19 pandemic has placed global health care systems under unprecedented strain but has, at the same time, provided a unique opportunity for pathologists to turn autopsy findings into directly actionable insights into patient care. The current data on the neuropathology of COVID-19 remains preliminary and is limited by the lack of suitable controls, but certain tentative conclusions can be drawn. SARS-CoV-2 can infect multiple cell types in the central nervous system and does so in a subset of patients, although the clinical significance of direct infections remains in the central nervous system (CNS) and the peripheral nervous system (PNS) infections remains unclear. The best-described neuropathological manifestations of COVID-19 in the brain are variable patterns of neuroinflammation and vascular injury, although again, it remains unclear to what degree these findings are specifically due to COVID-19. There is also intriguing preliminary data to suggest a complex relationship between COVID-19 and neurodegeneration, with certain alleles that increase AD risk also increasing the risk of severe COVID-19, and conversely, the possibility that COVID-19 may increase the risk of neurodegenerative disease. The neuropathology of so-called "long-COVID" and the potential effects of COVID-19, or critical illness in general, on neurodegenerative disease remains unclear. There is thus an urgent need for long-term cohort studies of COVID-19 survivors, including brain donation, particularly in elderly patients, with careful recruitment of controls with similar non-COVID inflammatory illnesses.


Subject(s)
COVID-19 , Neurodegenerative Diseases , Aged , Brain/pathology , Humans , Neurodegenerative Diseases/pathology , Pandemics , SARS-CoV-2
2.
Curr Opin Neurol ; 35(2): 212-219, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1662160

ABSTRACT

PURPOSE OF REVIEW: Does neuroinflammation promote neurodegeneration? Does neurodegeneration promote neuroinflammation? Or, is the answer to both questions, yes? These questions have proven challenging to answer in patients with typical age-related neurodegenerative diseases in whom the onset of neuroinflammation and neurodegeneration are largely unknown. Patients recovering from diseases associated with abrupt-onset neuroinflammation, including rare forms of antibody-mediated encephalitis (AME) and common complications of novel coronavirus disease 2019 (COVID-19), provide a unique opportunity to untangle the relationship between neuroinflammation and neurodegeneration. This review explores the lessons learned from patients with AME and COVID-19. RECENT FINDINGS: Persistent cognitive impairment is increasingly recognized in patients recovering from AME or COVID-19, yet the drivers of impairment remain largely unknown. Clinical observations, neuroimaging and biofluid biomarkers, and pathological studies imply a link between the severity of acute neuroinflammation, subsequent neurodegeneration, and disease-associated morbidity. SUMMARY: Data from patients with AME and COVID-19 inform key hypotheses that may be evaluated through future studies incorporating longitudinal biomarkers of neuroinflammation and neurodegeneration in larger numbers of recovering patients. The results of these studies may inform the contributors to cognitive impairment in patients with AME and COVID-19, with potential diagnostic and therapeutic applications in patients with age-related neurodegenerative diseases.


Subject(s)
COVID-19 , Encephalitis , Neurodegenerative Diseases , COVID-19/complications , Encephalitis/complications , Humans , Neurodegenerative Diseases/pathology , SARS-CoV-2
3.
Viruses ; 13(10)2021 10 17.
Article in English | MEDLINE | ID: covidwho-1471000

ABSTRACT

Coronavirus 2019 (COVID-19) is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the lungs. COVID-19 symptoms include the presence of fevers, dry coughs, fatigue, sore throat, headaches, diarrhea, and a loss of taste or smell. However, it is understood that SARS-CoV-2 is neurotoxic and neuro-invasive and could enter the central nervous system (CNS) via the hematogenous route or via the peripheral nerve route and causes encephalitis, encephalopathy, and acute disseminated encephalomyelitis (ADEM) in COVID-19 patients. This review discusses the possibility of SARS-CoV-2-mediated Multiple Sclerosis (MS) development in the future, comparable to the surge in Parkinson's disease cases following the Spanish Flu in 1918. Moreover, the SARS-CoV-2 infection is associated with a cytokine storm. This review highlights the impact of these modulated cytokines on glial cell interactions within the CNS and their role in potentially prompting MS development as a secondary disease by SARS-CoV-2. SARS-CoV-2 is neurotropic and could interfere with various functions of neurons leading to MS development. The influence of neuroinflammation, microglia phagocytotic capabilities, as well as hypoxia-mediated mitochondrial dysfunction and neurodegeneration, are mechanisms that may ultimately trigger MS development.


Subject(s)
COVID-19/complications , COVID-19/pathology , Central Nervous System/pathology , Multiple Sclerosis/pathology , Neurodegenerative Diseases/virology , Central Nervous System/virology , Cytokine Release Syndrome/pathology , Cytokines/blood , Cytokines/metabolism , History, 20th Century , Humans , Influenza Pandemic, 1918-1919/statistics & numerical data , Multiple Sclerosis/virology , Neurodegenerative Diseases/pathology , SARS-CoV-2/immunology
5.
J Environ Pathol Toxicol Oncol ; 40(3): 37-49, 2021.
Article in English | MEDLINE | ID: covidwho-1362158

ABSTRACT

It has now been almost a year since the emergence of the deadly SARS-CoV-2 with millions of people losing their lives due to resultant COVID-19. Apart from the well-known consequences of respiratory illnesses, it has even effortlessly mapped itself into the nervous system through routes like blood, CSF, neurons, and olfactory cells. Interestingly, the interaction of SARS-CoV-2 with the nervous system cells like neurons, microglia, and astrocytes has been a factor to worsen COVID-19 through its neuroinflammatory actions. The release of cytokines due to astrocyte and microglial activation could progress towards the most anticipated cytokine storm proving to be detrimental in the management of COVID-19. Such hyper-inflammatory conditions could make the BBB vulnerable, encouraging excessive viral particles into the CNS, leading to further neurodegenerative pathologies like Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and Multiple Sclerosis. Excessive neuroinflammation and neurodegeneration being the anticipated root causes of these multiple conditions, it is also essential to look into other factors that synergistically enhance the worsening of these diseases in COVID-19 patients for which additional studies are essential.


Subject(s)
COVID-19/etiology , Inflammation/virology , Neurodegenerative Diseases/pathology , SARS-CoV-2/pathogenicity , Cytokines/metabolism , Host-Pathogen Interactions , Humans , Inflammation/pathology , Microglia/pathology , Microglia/virology , Multiple Sclerosis/pathology , Multiple Sclerosis/virology , Neurodegenerative Diseases/virology , Neurons/pathology , Neurons/virology
6.
Int J Mol Sci ; 22(13)2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1304666

ABSTRACT

Epilepsy can be both a primary pathology and a secondary effect of many neurological conditions. Many papers show that neuroinflammation is a product of epilepsy, and that in pathological conditions characterized by neuroinflammation, there is a higher probability to develop epilepsy. However, the bidirectional mechanism of the reciprocal interaction between epilepsy and neuroinflammation remains to be fully understood. Here, we attempt to explore and discuss the relationship between epilepsy and inflammation in some paradigmatic neurological and systemic disorders associated with epilepsy. In particular, we have chosen one representative form of epilepsy for each one of its actual known etiologies. A better understanding of the mechanistic link between neuroinflammation and epilepsy would be important to improve subject-based therapies, both for prophylaxis and for the treatment of epilepsy.


Subject(s)
Disease Susceptibility , Epilepsy/etiology , Inflammation/complications , Animals , Biomarkers , Brain Neoplasms/complications , Brain Neoplasms/etiology , Brain Neoplasms/pathology , Combined Modality Therapy , Disease Management , Epilepsy/diagnosis , Epilepsy/metabolism , Epilepsy/therapy , Genetic Predisposition to Disease , Humans , Inflammation/etiology , Neurodegenerative Diseases/complications , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/pathology , Symptom Assessment , Treatment Outcome
7.
Int J Mol Sci ; 22(4)2021 Feb 18.
Article in English | MEDLINE | ID: covidwho-1110432

ABSTRACT

The mitochondrial respiratory chain is the main site of reactive oxygen species (ROS) production in the cell. Although mitochondria possess a powerful antioxidant system, an excess of ROS cannot be completely neutralized and cumulative oxidative damage may lead to decreasing mitochondrial efficiency in energy production, as well as an increasing ROS excess, which is known to cause a critical imbalance in antioxidant/oxidant mechanisms and a "vicious circle" in mitochondrial injury. Due to insufficient energy production, chronic exposure to ROS overproduction consequently leads to the oxidative damage of life-important biomolecules, including nucleic acids, proteins, lipids, and amino acids, among others. Different forms of mitochondrial dysfunction (mitochondriopathies) may affect the brain, heart, peripheral nervous and endocrine systems, eyes, ears, gut, and kidney, among other organs. Consequently, mitochondriopathies have been proposed as an attractive diagnostic target to be investigated in any patient with unexplained progressive multisystem disorder. This review article highlights the pathomechanisms of mitochondriopathies, details advanced analytical tools, and suggests predictive approaches, targeted prevention and personalization of medical services as instrumental for the overall management of mitochondriopathy-related cascading pathologies.


Subject(s)
Energy Metabolism , Mitochondria/pathology , Mitochondrial Diseases/pathology , Oxidative Stress , Animals , Carcinogenesis/pathology , Humans , Mitochondria/metabolism , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/metabolism , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Precision Medicine , Reactive Oxygen Species/metabolism
8.
Int J Mol Sci ; 22(4)2021 Feb 11.
Article in English | MEDLINE | ID: covidwho-1079664

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Currently, there is some information on the consequences of COVID-19 infection in multiple sclerosis (MS) patients, as it is a newly discovered coronavirus, but its far-reaching effects on participation in neurodegenerative diseases seem to be significant. Recent cases reports showed that SARS-CoV-2 may be responsible for initiating the demyelination process in people who previously had no symptoms associated with any nervous system disorders. It is presently known that infection of SARS-CoV-2 evokes cytokine storm syndrome, which may be one of the factors leading to the acute cerebrovascular disease. One of the substantial problems is the coexistence of cerebrovascular disease and MS in an individual's life span. Epidemiological studies showed an enhanced risk of death rate from vascular disabilities in MS patients of approximately 30%. It has been demonstrated that patients with severe SARS-CoV-2 infection usually show increased levels of D-dimer, fibrinogen, C-reactive protein (CRP), and overactivation of blood platelets, which are essential elements of prothrombotic events. In this review, the latest knowledge gathered during an ongoing pandemic of SARS-CoV-2 infection on the neurodegeneration processes in MS is discussed.


Subject(s)
COVID-19/complications , Multiple Sclerosis/complications , Neurodegenerative Diseases/etiology , Animals , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Humans , Multiple Sclerosis/pathology , Multiple Sclerosis/virology , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/virology , SARS-CoV-2/isolation & purification , Thrombosis/etiology , Thrombosis/pathology
9.
Drug Discov Ther ; 14(6): 262-272, 2021 Jan 23.
Article in English | MEDLINE | ID: covidwho-1067907

ABSTRACT

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2019 in Wuhan, China. Clinically, respiratory tract symptoms as well as other organs disorders are observed in patients positively diagnosed coronavirus disease 2019 (COVID-19). In addition, neurological symptoms, mainly anosmia, ageusia and headache were observed in many patients. Once in the central nervous system (CNS), the SARS-CoV-2 can reside either in a quiescent latent state, or eventually in actively state leading to severe acute encephalitis, characterized by neuroinflammation and prolonged neuroimmune activation. SRAS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor. The expression of this receptor in endothelial cells of blood-brain barrier (BBB) shows that SRAS-CoV-2 may have higher neuroinvasive potential compared to known coronaviruses. This review summarizes available information regarding the impact of SRAS-CoV-2 in the brain and tended to identify its potential pathways of neuroinvasion. We offer also an understanding of the long-term impact of latently form of SARS-CoV-2 on the development of neurodegenerative disorders. As a conclusion, the persistent infection of SRAS-CoV-2 in the brain could be involved on human neurodegenerative diseases that evolve a gradual process, perhapes, over several decades.


Subject(s)
COVID-19/virology , Central Nervous System Viral Diseases/virology , Neurodegenerative Diseases/virology , Neurons/virology , SARS-CoV-2/pathogenicity , Viral Tropism , Animals , COVID-19/complications , Central Nervous System Viral Diseases/metabolism , Central Nervous System Viral Diseases/pathology , Host-Pathogen Interactions , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/pathology , Neurons/metabolism , Neurons/pathology , Virus Latency
10.
ACS Chem Neurosci ; 11(24): 4012-4016, 2020 12 16.
Article in English | MEDLINE | ID: covidwho-983572

ABSTRACT

The current pandemic of coronavirus disease 2019 (COVID-19) has gained increased attention in the neuroscience community, especially taking into account the neuroinvasive potential of its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of its infection on the structure and function of the brain. Apart from the neurotropic properties of SARS-CoV-2, it is likewise important the observation that virus infection may perturb specific cellular processes that are believed to play an important role in the pathogenesis of diverse neurological disorders, particularly in Parkinson's disease (PD). In this scenario, viral infection-induced colon inflammation, gut microbial imbalance, and α-synuclein upregulation are of particular interest with regard to the interplay between the gastrointestinal tract and the central nervous system (microbiome-gut-brain axis). In this Perspective, we present a critical view on the different hypotheses that are recently being raised by neuroscientists about the relationship between SARS-CoV-2 infection and long-lasting neurodegenerative disorders, opening the question of whether COVID-19 might represent a risk factor for the development of PD.


Subject(s)
Dysbiosis/virology , Neurodegenerative Diseases/virology , SARS-CoV-2/pathogenicity , Virus Diseases/virology , Brain/pathology , Brain/virology , Dysbiosis/complications , Gastrointestinal Microbiome/physiology , Humans , Neurodegenerative Diseases/pathology , Virus Diseases/complications , Virus Diseases/pathology
11.
Aging (Albany NY) ; 12(23): 24453-24461, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-927217

ABSTRACT

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) uses the angiotensin-converting enzyme 2 (ACE2) receptor for infecting and spreading in humans. Studies have shown that the widespread expression of ACE2 in human tissues may be associated with organ function damage (e.g., lung, kidney, and stomach) in patients with coronavirus disease 2019 (COVID-19). However, in neurodegenerative diseases, whose pathogenesis is closely related to advanced age, ACE2 plays a neurotrophic and protective role by activating the ACE2/Ang-(1-7)/Mas axis, thus inhibiting cognitive impairment. Early reports have revealed that the elderly are more susceptible to COVID-19 and that elderly patients with COVID-19 have faster disease progression and higher mortality. Therefore, during the COVID-19 pandemic, it is crucial to understand the role of ACE2 in neurodegenerative diseases. In this paper, we review the relationship between COVID-19, neurodegenerative diseases, and ACE2, as well as provide recommendations for the protection of elderly patients with neurodegenerative diseases during the COVID-19 pandemic.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/virology , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/metabolism , SARS-CoV-2 , Age Factors , Angiotensin-Converting Enzyme 2/genetics , Disease Susceptibility , Host-Pathogen Interactions , Humans , Neurodegenerative Diseases/pathology , Renin-Angiotensin System , Risk Factors , SARS-CoV-2/physiology
13.
Alzheimers Res Ther ; 12(1): 69, 2020 06 04.
Article in English | MEDLINE | ID: covidwho-526712

ABSTRACT

Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.


Subject(s)
Betacoronavirus , Brain/virology , Coronavirus Infections/complications , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/virology , Pneumonia, Viral/complications , Animals , Brain/pathology , COVID-19 , Coronavirus Infections/pathology , Humans , Neurodegenerative Diseases/pathology , Pandemics , Pneumonia, Viral/pathology , SARS-CoV-2 , Time Factors
14.
ACS Chem Neurosci ; 11(13): 1887-1899, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-505648

ABSTRACT

The coronavirus disease-19 (COVID-19) pandemic has emerged as one of the major outbreaks to be mentioned in history in coming times. Like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a respiratory virus infecting the lungs with fever, dry cough, and acute pneumonia being the major symptoms. It infects epithelial cells expressing angiotensin converting enzyme 2 (ACE2) receptor, which is crucial for viral entry. Based on evolving clinical evidence, it is now unfitting to label SARS-CoV-2 as just a respiratory virus, as lately there are various reports that substantiate its pathogenicity in other organs of the body, including brain. In this review, we discuss the epidemiology of SARS-CoV-2 in comparison to SARS and MERS along with possibilities of viral entry into central nervous system (CNS) tissues. The review provides detailed information about the virulence, epidemiology, and insights into molecular pathways involved in the infectivity of the SARS-CoV-2 virus, along with an in-depth view of current concepts about the neurological significance of the SARS-CoV-2 virus and its neuropathological competence. The review also touches upon our current understanding of placental transmission of SARS-CoV-2, an important aspect of vertical transmission. Furthermore, the review provides a current update on strategies that have been used, are being used, or are under trial for treating the disease.


Subject(s)
Betacoronavirus/metabolism , Brain/metabolism , Coronavirus Infections/metabolism , Neurodegenerative Diseases/metabolism , Pneumonia, Viral/metabolism , Angiotensin-Converting Enzyme 2 , Brain/pathology , Brain/virology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Humans , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/virology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/metabolism , Severe Acute Respiratory Syndrome/pathology
SELECTION OF CITATIONS
SEARCH DETAIL