scholarly journals Neuropathogenesis of SARS-CoV-2 infection

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shumayila Khan ◽  
James Gomes
Keyword(s):  
Nervous System ◽  
Human Life ◽  
Neurological Complications ◽  
Pulmonary Complications ◽  
Neurological Damage ◽  
Sensory Impairments ◽  
Low Levels ◽  
Chief Symptom ◽  
The Brain ◽  
Initial Knowledge

The COVID-19 pandemic caused by the SARS-CoV-2 has recently emerged as a serious jolt to human life and economy. Initial knowledge established pulmonary complications as the chief symptom, however, the neurological aspect of the disease is also becoming increasingly evident. Emerging reports of encephalopathies and similar ailments with the detection of the virus in the CSF has elicited an urgent need for investigating the possibility of neuroinvasiveness of the virus, which cannot be ruled out given the expression of low levels of ACE2 receptors in the brain. Sensory impairments of the olfactory and gustatory systems have also been reported in a large proportion of the cases, indicating the involvement of the peripheral nervous system. Hence, the possibility of neurological damage caused by the virus demands immediate attention and investigation of the mechanisms involved, so as to customize the treatment of patients presenting with neurological complications.

Neurological symptoms of COVID-19

2021 ◽  
Vol 36 (4) ◽  
pp. 285-296
Author(s):  
Adriana Wawer ◽  
Agnieszka Piechal
Keyword(s):  
Nervous System ◽  
Viral Infections ◽  
Harmful Effect ◽  
Neurological Complications ◽  
Neurological Symptoms ◽  
Acute Respiratory Disease ◽  
Neurological Damage ◽  
Impaired Consciousness ◽  
Potential Impact ◽  
The Brain

Objective. Some viral infections can have a harmful effect on the functioning of the nervous system and can even cause serious neurological damage. This work aims to review the results of studies published so far concerning neurological complications in people infected with coronaviruses, especially SARS-CoV-2, and possible mechanisms responsible for nervous system damage. Literature review. Recently, there have been reports that coronaviruses, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), cause acute respiratory disease, exhibit neurotropic properties and can also cause neurological symptoms. There are studies published showing that these viruses may penetrate to the brain and cerebrospinal fluid. Conclusions. Coronaviruses are still poorly understood, so it seems important to study the potential impact of SARS-CoV-2 infections on the nervous system. It seems appropriate that patients infected with SARS-CoV-2 should be early evaluated for neurological symptoms, including headache and impaired consciousness.

scholarly journals Simian Immunodeficiency Virus-Infected Memory CD4+ T Cells Infiltrate to the Site of Infected Macrophages in the Neuroparenchyma of a Chronic Macaque Model of Neurological Complications of AIDS

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Cheri A. Lee ◽  
Erin Beasley ◽  
Karthikeyan Sundar ◽  
Margery Smelkinson ◽  
Carol Vinton ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
B Cells ◽  
Mononuclear Cells ◽  
Rhesus Macaques ◽  
Neurological Complications ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Simian immunodeficiency virus (SIV)-infected nonhuman primates can serve as a relevant model for AIDS neuropathogenesis. Current SIV-induced encephalitis (SIVE)/neurological complications of AIDS (neuroAIDS) models are generally associated with rapid progression to neuroAIDS, which does not reflect the tempo of neuroAIDS progression in humans. Recently, we isolated a neuropathogenic clone, SIVsm804E-CL757 (CL757), obtained from an SIV-infected rhesus macaque (RM). CL757 causes a more protracted progression to disease, inducing SIVE in 50% of inoculated animals, with high cerebral spinal fluid viral loads, multinucleated giant cells (MNGCs), and perivascular lymphocytic cuffing in the central nervous system (CNS). This latter finding is reminiscent of human immunodeficiency virus (HIV) encephalitis in humans but not generally observed in rapid progressor animals with neuroAIDS. Here, we studied which subsets of cells within the CNS were targeted by CL757 in animals with neurological symptoms of SIVE. Immunohistochemistry of brain sections demonstrated infiltration of CD4+ T cells (CD4) and macrophages (MΦs) to the site of MNGCs. Moreover, an increase in mononuclear cells isolated from the brain tissues of RMs with SIVE correlated with increased cerebrospinal fluid (CSF) viral load. Subset analysis showed a specific increase in brain CD4+ memory T cells (Br-mCD4), brain-MΦs (Br-MΦs), and brain B cells (Br-B cells). Both Br-mCD4s and Br-MΦs harbored replication-competent viral DNA, as demonstrated by virus isolation by coculture. However, only in animals exhibiting SIVE/neuroAIDS was virus isolated from Br-MΦs. These findings support the use of CL757 to study the pathogenesis of AIDS viruses in the central nervous system and indicate a previously unanticipated role of CD4s cells as a potential reservoir in the brain. IMPORTANCE While the use of combination antiretroviral therapy effectively suppresses systemic viral replication in the body, neurocognitive disorders as a result of HIV infection of the central nervous system (CNS) remain a clinical problem. Therefore, the use of nonhuman primate models is necessary to study mechanisms of neuropathogenesis. The neurotropic, molecular clone SIVsm804E-CL757 (CL757) results in neuroAIDS in 50% of infected rhesus macaques approximately 1 year postinfection. Using CL757-infected macaques, we investigate disease progression by examining subsets of cells within the CNS that were targeted by CL757 and could potentially serve as viral reservoirs. By isolating mononuclear cells from the brains of SIV-infected rhesus macaques with and without encephalitis, we show that immune cells invade the neuroparenchyma and increase in number in the CNS in animals with SIV-induced encephalitis (SIVE). Of these cells, both brain macrophages and brain memory CD4+ T cells harbor replication-competent SIV DNA; however, only brain CD4+ T cells harbored SIV DNA in animals without SIVE. These findings support use of CL757 as an important model to investigate disease progression in the CNS and as a model to study virus reservoirs in the CNS.

scholarly journals Clinical characteristics of Epstein–Barrvirus infection in the pediatric nervous system

2020 ◽  
Author(s):  
Huan Cheng ◽  
Doudou Chen ◽  
XiaoLing Peng ◽  
Peng wu ◽  
Li Jang ◽  
...  
Keyword(s):  
Nervous System ◽  
Clinical Characteristics ◽  
Axonal Neuropathy ◽  
Acute Disseminated Encephalomyelitis ◽  
Neurological Complications ◽  
Clinical Feature ◽  
Neurological Damage ◽  
Acute Motor Axonal Neuropathy ◽  
Barr Virus ◽  
Ebv Infection

Abstract Background: To investigate the clinical characteristics of Epstein–Barr virus (EBV) infection in the pediatric nervous system (NS).Methods: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019.Results: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0–4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain–Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV.Conclusion: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.

scholarly journals Clinical characteristics of Epstein–Barrvirus infection in the pediatric nervous system

2020 ◽  
Author(s):  
Huan Cheng ◽  
DouDou Chen ◽  
XiaoLing Peng ◽  
Peng wu ◽  
Li Jang ◽  
...  
Keyword(s):  
Nervous System ◽  
Clinical Characteristics ◽  
Axonal Neuropathy ◽  
Acute Disseminated Encephalomyelitis ◽  
Neurological Complications ◽  
Clinical Feature ◽  
Neurological Damage ◽  
Acute Motor Axonal Neuropathy ◽  
Barr Virus ◽  
Ebv Infection

Abstract Background: To investigate the clinical characteristics of Epstein–Barr virus (EBV) infection in the pediatric nervous system (NS). Methods: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019. Results: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0–4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain–Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV. Conclusion: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.

scholarly journals Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages

2004 ◽  
Vol 78 (13) ◽  
pp. 6915-6926 ◽  
Author(s):  
Paul J. Peters ◽  
Jayanta Bhattacharya ◽  
Samantha Hibbitts ◽  
Matthias T. Dittmar ◽  
Graham Simmons ◽  
...  
Keyword(s):  
Lymph Node ◽  
Brain Tissue ◽  
Neurological Complications ◽  
Macrophage Tropism ◽  
Immunodeficiency Virus ◽  
Autopsy Brain Tissue ◽  
Low Levels ◽  
The Brain ◽  
Ccr5 Inhibitor

ABSTRACT Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4+ CCR5+ cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.

scholarly journals Clinical Characteristics of Epstein–Barrvirus Infection in the Pediatric Nervous System

2020 ◽  
Author(s):  
Huan Cheng ◽  
DouDou Chen ◽  
XiaoLing Peng ◽  
Peng wu ◽  
Li Jang ◽  
...  
Keyword(s):  
Nervous System ◽  
Clinical Characteristics ◽  
Axonal Neuropathy ◽  
Acute Disseminated Encephalomyelitis ◽  
Neurological Complications ◽  
Clinical Feature ◽  
Neurological Damage ◽  
Acute Motor Axonal Neuropathy ◽  
Barr Virus ◽  
Ebv Infection

Abstract Background: To investigate the clinical characteristics of Epstein–Barr virus (EBV) infection in the pediatric nervous system (NS).Methods: We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children's hospital of Chongqing Medical University from January 2008 to April 2019.Results: EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0–4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain–Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV.Conclusion: There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.

scholarly journals Neurological update: COVID-19

2021 ◽  
Author(s):  
A. L. Ren ◽  
R. J. Digby ◽  
E. J. Needham
Keyword(s):  
Nervous System ◽  
Critical Illness ◽  
Severe Acute Respiratory Syndrome ◽  
Cerebrovascular Disease ◽  
Respiratory System ◽  
Neurological Disorders ◽  
Neurological Complications ◽  
Significant Issue ◽  
Neurological Damage ◽  
Direct Invasion

AbstractCoronavirus Disease 2019 is predominantly a disorder of the respiratory system, but neurological complications have been recognised since early in the pandemic. The major pathophysiological processes leading to neurological damage in COVID-19 are cerebrovascular disease, immunologically mediated neurological disorders and the detrimental effects of critical illness on the nervous system. It is still unclear whether direct invasion of the nervous system by the Severe Acute Respiratory Syndrome Coronavirus 2 occurs; given the vast numbers of people infected at this point, this uncertainty suggests that nervous system infection is unlikely to represent a significant issue if it occurs at all. In this review, we explore what has been learnt about the neurological complications of COVID-19 over the course of the pandemic, and by which mechanisms these complications most commonly occur.

Chronic central nervous system exposure to interleukin-1 beta causes catabolism in the rat

1996 ◽  
Vol 271 (5) ◽  
pp. R1142-R1148 ◽  
Author(s):  
A. G. Hill ◽  
L. Jacobson ◽  
J. Gonzalez ◽  
J. Rounds ◽  
J. A. Majzoub ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Weight Loss ◽  
Nervous System ◽  
Interleukin 1 ◽  
Plasma Corticosterone ◽  
Cns Injury ◽  
Intracerebroventricular Infusion ◽  
Low Levels ◽  
The Brain ◽  
Cns Exposure

Interleukin-1 (IL-1) and interleukin-6 (IL-6) are thought to play a role in mediating weight loss, net protein catabolism, anorexia, and fever after infection or injury. Because IL-1 and IL-6 can be synthesized in the brain and have been shown to be increased in central nervous system (CNS) infections, we investigated the metabolic consequences of prolonged CNS exposure to these cytokines. At equivalent doses, intracerebroventricular infusion of IL-1, but not IL-6, caused negative nitrogen balance, weight loss, and anorexia. Intracerebroventricular infusion of IL-1 also caused adrenocortical activation, as indicated by increased adrenal weight and plasma corticosterone, and decreased thymus weight. However, clamping plasma glucocorticoids at low levels by adrenalectomy and corticosterone pellet replacement did not attenuate IL-1-induced losses of body weight and nitrogen. We conclude that centrally produced IL-1 could play an important role in the metabolic alterations associated with CNS injury or infection and that these effects may not be solely attributable to increased secretion of glucocorticoids.

scholarly journals Neurological complications and infection mechanism of SARS-COV-2

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dandan Wan ◽  
Tingfu Du ◽  
Weiqi Hong ◽  
Li Chen ◽  
Haiying Que ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Respiratory Diseases ◽  
Neurological Diseases ◽  
Neurological Complications ◽  
Experimental Models ◽  
Current Evidence ◽  
Global Pandemic ◽  
The Central Nervous System ◽  
The Brain

AbstractCurrently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established. In this review, we primarily describe the clinical neurological complications associated with SARS-CoV-2 and discuss the potential mechanisms through which SARS-CoV-2 invades the brain based on the current evidence. Finally, we summarize the experimental models were used to study SARS-CoV-2 neuroinvasion. These data form the basis for studies on the significance of SARS-CoV-2 infection in the brain.

scholarly journals Hemorrhagic Encephalitis after COVID-19 (Clinical Case)

2021 ◽  
Vol 6 (6) ◽  
pp. 152-157
Author(s):  
I. O. Filiuk ◽  
◽  
O. I. Kalbus ◽  
N. P. Shastun ◽  
D. I. Andreichenko ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Neurological Disorders ◽  
Clinical Case ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Neurological Complications ◽  
Diagnostic Features ◽  
Time Of Admission ◽  
The Brain

COVID-19 is an urgent problem all over the world that affects not only the respiratory system, but also causes many neurological disorders. In connection with the clinical manifestations of COVID-19, further detailed study of neurological complications is required, such as ischemic and hemorrhagic strokes, damage to the peripheral nervous system, and inflammatory diseases of the brain. Some neurological symptoms after an illness may persist for several weeks or even months. Hemorrhagic encephalitis is one such complication of COVID-19. Taking into account the growth of COVID-19 and frequent neurological complications after a previous illness, more and more often patients will seek medical help from a specialist, such as a neurologist, psychologist, psychiatrist. The only protection against COVID-19, which causes serious complications, is vaccination. The purpose of the study was to highlight a rare case of hemorrhagic encephalitis, which developed against the background of the previous COVID-19 disease. Materials and methods. The work is based on a description of a clinical case of hemorrhagic encephalitis in a patient who has undergone COVID-19. The modern literature data on the clinical and diagnostic features and therapeutic possibilities of hemorrhagic encephalitis are presented. Results and discussion. The article examines data on the clinical manifestations of COVID-19, which can occur in both mild and severe forms, reflects the diagnostic criteria of this disease, highlights treatment approaches, discusses in detail and provides data on the main aspects of the pathogenetic mechanisms underlying development of the disease. Complications of COVID-19 have been described, not only from the central and peripheral nervous system, but also from other systems. The second part of the article is presented in the form of a clinical case of hemorrhagic encephalitis against the background of the undergone COVID-19, which was recorded in our hospital. This part of the article describes in detail the patient's complaints and anamnestic data, the data of the somatic and neurological examination at the time of admission to the hospital and in dynamics, and describes the treatment tactics. Attention is especially focused on the cognitive functions of this patient, which will become the reason for seeing a psychiatrist in the future. Conclusion. Neurological complications of COVID-19 are increasingly registered, requiring close attention from neurologists. Hemorrhagic encephalitis can be one of these complications

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