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1.
Curr Opin Neurol ; 36(3): 198-206, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-2301461

ABSTRACT

PURPOSE OF THE REVIEW: Persistent infections capable of causing central nervous system (CNS) complications months or years after the initial infection represent a major public health concern. This concern is particularly relevant considering the ongoing coronavirus disease 2019 pandemic, where the long-term neurological effects are still being recognized. RECENT FINDINGS: Viral infections are a risk factor for the development of neurodegenerative diseases. In this paper, we provide an in-depth exploration of the prevalent known and suspected persistent pathogens and their epidemiological and mechanistic links to later development of CNS disease. We examine the pathogenic mechanisms involved, including direct viral damage and indirect immune dysregulation, while also addressing the challenges associated with detecting persistent pathogens. SUMMARY: Viral encephalitis has been closely associated with the later development of neurodegenerative diseases and persistent viral infections of the CNS can result in severe and debilitating symptoms. Further, persistent infections may result in the development of autoreactive lymphocytes and autoimmune mediated tissue damage. Diagnosis of persistent viral infections of the CNS remains challenging and treatment options are limited. The development of additional testing modalities as well as novel antiviral agents and vaccines against these persistent infections remains a crucial research goal.


Subject(s)
COVID-19 , Central Nervous System Diseases , Virus Diseases , Humans , Persistent Infection , COVID-19/complications , Virus Diseases/complications
2.
Biomolecules ; 13(1)2023 01 13.
Article in English | MEDLINE | ID: covidwho-2199743

ABSTRACT

Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of "endogenous players", such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS). Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and "Long-COVID". Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.


Subject(s)
COVID-19 , Central Nervous System Diseases , Gastrointestinal Microbiome , Humans , SARS-CoV-2 , Brain-Gut Axis , Mitochondria
3.
CNS Neurosci Ther ; 29(2): 538-543, 2023 02.
Article in English | MEDLINE | ID: covidwho-2152653

ABSTRACT

INTRODUCTION: Data on structural brain changes after infection with SARS-CoV-2 is sparse. We postulate multiple sclerosis as a model to study the effects of SARS-CoV-2 on brain atrophy due to the unique availability of longitudinal imaging data in this patient group, enabling assessment of intraindividual brain atrophy rates. METHODS: Global and regional cortical gray matter volumes were derived from structural MRIs using FreeSurfer. A linear model was fitted to the measures of the matching pre-SARS-CoV-2 images with age as an explanatory variable. The residuals were used to determine whether the post-SARS-CoV-2 volumes differed significantly from the baseline. RESULTS: Fourteen RRMS patients with a total of 113 longitudinal magnetic resonance images were retrospectively analyzed. We found no acceleration of brain atrophy after infection with SARS-CoV-2 for global gray matter volume (p = 0.17). However, on the regional level, parahippocampal gyri showed a tendency toward volume reduction (p = 0.0076), suggesting accelerated atrophy during or after infection. CONCLUSIONS: Our results illustrate the opportunity of using longitudinal MRIs from existing MS registries to study brain changes associated with SARS-CoV-2 infections. We would like to address the global MS community with a call for action to use the available cohorts, reproduce the proposed analysis, and pool the results.


Subject(s)
COVID-19 , Central Nervous System Diseases , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Multiple Sclerosis/diagnostic imaging , SARS-CoV-2 , Retrospective Studies , COVID-19/diagnostic imaging , COVID-19/pathology , Brain/diagnostic imaging , Brain/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Magnetic Resonance Imaging/methods , Central Nervous System Diseases/pathology , Atrophy/pathology
4.
J Neuroimmunol ; 371: 577939, 2022 10 15.
Article in English | MEDLINE | ID: covidwho-1966866

ABSTRACT

BACKGROUND: Over the past two years, SARS-CoV-2 has frequently been documented with various post and para-infectious complications, including cerebrovascular, neuromuscular, and some demyelinating conditions such as acute disseminated encephalomyelitis (ADEM). We report two rare neurological manifestations post-COVID-19 infection; multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Further, we reviewed other CNS inflammatory demyelinating diseases (IDDs) associated with SARS-CoV-2, including optic neuritis (ON) and neuromyelitis optica spectrum disorders (NMOSD). METHODS: A descriptive analysis and literature search of Google Scholar and PubMed was conducted by two independent reviewers from December 1st, 2019, to March 30th, 2022, and included all the case studies of MS, MOGAD, NMOSD, and ON associated with COVID-19 infection. CASE PRESENTATIONS: Case 1 (MS) was a 24-year-old female with paresthesia and bilateral weakness one week after COVID-19 symptom onset who showed demyelinating plaques and 12 isolated oligoclonal bands (OCBs). Case 2 (MOGAD) was a 41-year-old male with encephalomyelitis 16 days after COVID-19, who later developed MOG-antibody-associated optic neuritis. RESULTS: Out of 18 cases, NMOSD was the most common post-COVID manifestation (7, 39%), followed by MOGAD (5, 28%), MS (4, 22%), and isolated ON (2, 11%). The median duration between the onset of COVID-19 symptom onset and neurological symptoms was 14 days. 61% of these were male, with a mean age of 35 years. IVMP was the treatment of choice, and nearly all patients made a full recovery, with zero fatalities. CONCLUSIONS: Although these neurological sequelae are few, physicians must be cognizant of their underlying pathophysiology and associated clinical and neuro-diagnostic findings when treating COVID-19 patients with atypical presentations.


Subject(s)
COVID-19 , Central Nervous System Diseases , Multiple Sclerosis , Neuromyelitis Optica , Optic Neuritis , Aquaporin 4 , Autoantibodies , COVID-19/complications , Central Nervous System , Female , Humans , Male , Myelin-Oligodendrocyte Glycoprotein , Neuromyelitis Optica/diagnosis , Optic Neuritis/diagnosis , Optic Neuritis/etiology , SARS-CoV-2
6.
Neurol Neurochir Pol ; 56(2): 118-130, 2022.
Article in English | MEDLINE | ID: covidwho-1887304

ABSTRACT

INTRODUCTION: Neuropathological brain and spinal cord post mortem examination is a distinct procedure that still plays an important role in modern medicine. In front of increasing amounts of clinical and genetic data, together with important developments in the field of neuroimaging, the Polish Association of Neuropathologists have updated their recommendations regarding central nervous system (CNS) examination. These guidelines are aimed at neuropathologists, pathologists and clinicians. AIM OF THE STUDY: Presentation of the outlined recommendations as their goal is to improve the quality, informativity, and cost effectiveness of CNS post mortem examinations. A comprehensive study of the literature was conducted to provide a clinical background of neuropathological autopsy. There are numerous open questions in neuroscience, and new strategies are required to foster research in CNS diseases. These include the challenge of organizing brain banks tasked with managing and protecting detailed multidisciplinary information about their resources. Complex neuropathological analyses of post mortem series are also important to assess the effectiveness of diagnostics and therapy, identify environmental impact on the development of neurological disorders, and improve public health policy. The recommendations outline the need for collaboration between multiple specialists to establish the proper diagnosis and to broaden knowledge of neurological disorders.


Subject(s)
Central Nervous System Diseases , Neuropathology , Autopsy/methods , Brain/pathology , Central Nervous System Diseases/pathology , Humans , Neuroimaging
7.
Front Immunol ; 13: 833548, 2022.
Article in English | MEDLINE | ID: covidwho-1771039

ABSTRACT

The direct impact and sequelae of infections in children and adults result in significant morbidity and mortality especially when they involve the central (CNS) or peripheral nervous system (PNS). The historical understanding of the pathophysiology has been mostly focused on the direct impact of the various pathogens through neural tissue invasion. However, with the better understanding of neuroimmunology, there is a rapidly growing realization of the contribution of the innate and adaptive host immune responses in the pathogenesis of many CNS and PNS diseases. The balance between the protective and pathologic sequelae of immunity is fragile and can easily be tipped towards harm for the host. The matter of immune privilege and surveillance of the CNS/PNS compartments and the role of the blood-brain barrier (BBB) and blood nerve barrier (BNB) makes this even more complex. Our understanding of the pathogenesis of many post-infectious manifestations of various microbial agents remains elusive, especially in the diverse African setting. Our exploration and better understanding of the neuroimmunology of some of the infectious diseases that we encounter in the continent will go a long way into helping us to improve their management and therefore lessen the burden. Africa is diverse and uniquely poised because of the mix of the classic, well described, autoimmune disease entities and the specifically "tropical" conditions. This review explores the current understanding of some of the para- and post-infectious autoimmune manifestations of CNS and PNS diseases in the African context. We highlight the clinical presentations, diagnosis and treatment of these neurological disorders and underscore the knowledge gaps and perspectives for future research using disease models of conditions that we see in the continent, some of which are not uniquely African and, where relevant, include discussion of the proposed mechanisms underlying pathogen-induced autoimmunity. This review covers the following conditions as models and highlight those in which a relationship with COVID-19 infection has been reported: a) Acute Necrotizing Encephalopathy; b) Measles-associated encephalopathies; c) Human Immunodeficiency Virus (HIV) neuroimmune disorders, and particularly the difficulties associated with classical post-infectious autoimmune disorders such as the Guillain-Barré syndrome in the context of HIV and other infections. Finally, we describe NMDA-R encephalitis, which can be post-HSV encephalitis, summarise other antibody-mediated CNS diseases and describe myasthenia gravis as the classic antibody-mediated disease but with special features in Africa.


Subject(s)
Brain Diseases , COVID-19 , Central Nervous System Diseases , Communicable Diseases , Encephalitis , Peripheral Nervous System Diseases , Adult , Autoimmunity , Central Nervous System , Child , Humans , Peripheral Nervous System
8.
Eur J Immunol ; 52(3): 503-510, 2022 03.
Article in English | MEDLINE | ID: covidwho-1718287

ABSTRACT

Corona disease 2019 (COVID-19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID-19 severity. However, several questions pertain with respect to the metabolome in COVID-19. We performed an in-depth assessment of 1129 unique metabolites in 27 hospitalized COVID-19 patients and integrated results with large-scale proteomic and immunology data to capture multiorgan system perturbations. More than half of the detected metabolic alterations in COVID-19 were driven by patient-specific confounding factors ranging from comorbidities to xenobiotic substances. Systematically adjusting for this, a COVID-19-specific metabolic imprint was defined which, over time, underwent a switch in response to severe acute respiratory syndrome coronavirus-2 seroconversion. Integration of the COVID-19 metabolome with clinical, cellular, molecular, and immunological severity scales further revealed a network of metabolic trajectories aligned with multiple pathways for immune activation, and organ damage including neurological inflammation and damage. Altogether, this resource refines our understanding of the multiorgan system perturbations in severe COVID-19 patients.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Metabolome/immunology , SARS-CoV-2 , Adolescent , Adult , Aged , COVID-19/complications , Case-Control Studies , Central Nervous System Diseases/etiology , Central Nervous System Diseases/immunology , Central Nervous System Diseases/metabolism , Cohort Studies , Female , Humans , Male , Metabolomics , Middle Aged , Organ Specificity , Pandemics , Phenotype , Proteomics , Severity of Illness Index , Young Adult
9.
Int J Biol Sci ; 18(2): 707-716, 2022.
Article in English | MEDLINE | ID: covidwho-1627058

ABSTRACT

The Coronavirus disease 2019 (COVID-19)" caused by the "severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)" has caused huge losses to the world due to the unavailability of effective treatment options. It is now a serious threat to humans as it causes severe respiratory disease, neurological complications, and other associated problems. Although COVID-19 generally causes mild and recoverable symptoms in children, it can cause serious severe symptoms and death causing complications. Most importantly, SARS-CoV-2 can cause neurological complications in children, such as shortness of breath, myalgia, stroke, and encephalopathy. These problems are highly linked with cytokine storm and proinflammatory responses, which can alter the physiology of the blood-brain barrier and allow the virus to enter the brain. Despite the direct infection caused by the virus entry into the brain, these neurological complications can result from indirect means such as severe immune responses. This review discusses viral transmission, transport to the brain, the associated prenatal stress, and neurological and/or immunological complications in children.


Subject(s)
COVID-19/immunology , COVID-19/pathology , Central Nervous System Diseases/etiology , SARS-CoV-2 , COVID-19/complications , Child , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Prenatal Exposure Delayed Effects
10.
Front Immunol ; 12: 782731, 2021.
Article in English | MEDLINE | ID: covidwho-1581325

ABSTRACT

The SARS-CoV-2 and its variants are still hitting the world. Ever since the outbreak, neurological involvements as headache, ageusia, and anosmia in COVID-19 patients have been emphasized and reported. But the pathogenesis of these new-onset neurological manifestations in COVID-19 patients is still obscure and controversial. As difficulty always lay in the diagnosis of neurological infection, current reports to validate the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) almost relied on the basic methods and warranted improvement. Here we reported a case series of 8 patients with prominent new-onset neurological manifestations, who were screened out from a patch of 304 COVID-19 confirmed patients. Next-generation sequencing (NGS) and proteomics were conducted in the simultaneously obtained CSF and serum samples of the selected patients, with three non-COVID-19 patients with matched demographic features used as the controls for proteomic analysis. SARS-CoV-2 RNA was detected in the CSF of four COVID-19 patients and was suspicious in the rest four remaining patients by NGS, but was negative in all serum samples. Proteomic analysis revealed that 185 and 59 proteins were differentially expressed in CSF and serum samples, respectively, and that only 20 proteins were shared, indicating that the proteomic changes in CSF were highly specific. Further proteomic annotation highlighted the involvement of complement system, PI3K-Akt signaling pathway, enhanced cellular interaction, and macrophages in the CSF proteomic alterations. This study, equipped with NGS and proteomics, reported a high detection rate of SARS-CoV-2 in the CSF of COVID-19 patients and the proteomic alteration of CSF, which would provide insights into understanding the pathological mechanism of SARS-CoV-2 CNS infection.


Subject(s)
COVID-19/cerebrospinal fluid , Central Nervous System Diseases/virology , Cerebrospinal Fluid/metabolism , Cerebrospinal Fluid/virology , RNA, Viral/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Proteomics , SARS-CoV-2 , Sequence Analysis, RNA
11.
Int J Mol Sci ; 22(24)2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1572492

ABSTRACT

Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug-drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/genetics , Drug-Related Side Effects and Adverse Reactions/metabolism , Pharmacogenetics/trends , Biomarkers , Cardiovascular Diseases/drug therapy , Central Nervous System Diseases/drug therapy , Cost-Benefit Analysis , Drug Development , Genotype , Humans , Neoplasms/drug therapy , Pharmaceutical Preparations , Pharmacogenetics/methods , Phenotype , COVID-19 Drug Treatment
12.
Am J Physiol Cell Physiol ; 322(1): C1-C11, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1533102

ABSTRACT

SARS-CoV-2 has rapidly spread across the globe and infected hundreds of millions of people worldwide. As our experience with this virus continues to grow, our understanding of both short-term and long-term complications of infection with SARS-CoV-2 continues to grow as well. Just as there is heterogeneity in the acute infectious phase, there is heterogeneity in the long-term complications seen following COVID-19 illness. The purpose of this review article is to present the current literature with regards to the epidemiology, pathophysiology, and proposed management algorithms for the various long-term sequelae that have been observed in each organ system following infection with SARS-CoV-2. We will also consider future directions, with regards to newer variants of the virus and their potential impact on the long-term complications observed.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , SARS-CoV-2 , Algorithms , COVID-19/etiology , Cardiovascular Diseases/etiology , Central Nervous System Diseases/etiology , Disease Progression , Hematologic Diseases/etiology , Humans , Post-Acute COVID-19 Syndrome
13.
BMJ Case Rep ; 14(11)2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1515262

ABSTRACT

Sarcoidosis is a systemic, idiopathic and granulomatous disease, which most commonly affects the skin, lungs and lymph nodes but can affect virtually any organ. Neurosarcoidosis can be the presenting or the only clinical manifestation accounting for 5%-15% of sarcoid diagnoses. In contrast to uveitis which is the most common ophthalmic manifestation, neuro-ophthalmic signs are uncommon in sarcoidosis. Optic neuropathy is the most common neuro-ophthalmic sign (70% in one series). Sarcoid-related optic neuropathy commonly presents with a picture similar to optic neuritis. Less commonly, optic nerve involvement occurs secondary to compressive lesions, or from direct granulomatous infiltration. Neuroimaging is crucial to identify the location of the lesion. We describe a case of sarcoid-related compressive optic neuropathy and third nerve palsy and highlight the challenging nature of neurosarcoidosis in a patient without a prior diagnosis of the disease.


Subject(s)
Central Nervous System Diseases , Oculomotor Nerve Diseases , Optic Nerve Diseases , Sarcoidosis , Central Nervous System Diseases/complications , Central Nervous System Diseases/diagnosis , Humans , Optic Nerve , Optic Nerve Diseases/diagnosis , Optic Nerve Diseases/etiology , Sarcoidosis/complications , Sarcoidosis/diagnosis
14.
Diabetes Metab Syndr ; 15(6): 102305, 2021.
Article in English | MEDLINE | ID: covidwho-1506436

ABSTRACT

Covid-19 associated several neurological manifestation in the form of Post-infectious transverse myelitis(TM) and para-infectious TM has been reported. A 54 years old female patient presented to us with acute retention of urine and upper motor neuron type of bilateral lower limb weakness in shock stage, after 12 days of covid-19 infection. MRI (3T) brain and spine showed no abnormality and Nerve conduction study showed acquired motor axonal polyradiculoneuropathy in bilateral lower limbs. We herein present an index case of MRI-negative myeloradiculoneuropathy following covid-19 infection.


Subject(s)
COVID-19/complications , Central Nervous System Diseases/pathology , Magnetic Resonance Imaging/methods , Motor Neuron Disease/pathology , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Central Nervous System Diseases/etiology , Female , Humans , Middle Aged , Motor Neuron Disease/etiology
15.
Acta Neuropathol ; 142(6): 923-936, 2021 12.
Article in English | MEDLINE | ID: covidwho-1459953

ABSTRACT

As extremely sensitive immune cells, microglia act as versatile watchdogs of the central nervous system (CNS) that tightly control tissue homeostasis. Therefore, microglial activation is an early and easily detectable hallmark of virtually all neuropsychiatric, neuro-oncological, neurodevelopmental, neurodegenerative and neuroinflammatory diseases. The recent introduction of novel high-throughput technologies and several single-cell methodologies as well as advances in epigenetic analyses helped to identify new microglia expression profiles, enhancer-landscapes and local signaling cues that defined diverse previously unappreciated microglia states in the healthy and diseased CNS. Here, we give an overview on the recent developments in the field of microglia biology and provide a practical guide to analyze disease-associated microglia phenotypes in both the murine and human CNS, on several morphological and molecular levels. Finally, technical limitations, potential pitfalls and data misinterpretations are discussed as well.


Subject(s)
Microglia , Animals , Central Nervous System Diseases/pathology , Humans , Mice , Neuropathology , Phenotype
16.
Viruses ; 13(7)2021 07 15.
Article in English | MEDLINE | ID: covidwho-1448933

ABSTRACT

Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.


Subject(s)
Central Nervous System Diseases/virology , Central Nervous System Infections/epidemiology , Prion Diseases/epidemiology , Alphavirus/pathogenicity , Brazil/epidemiology , Central Nervous System/virology , Central Nervous System Diseases/metabolism , Central Nervous System Diseases/physiopathology , Central Nervous System Infections/virology , Central Nervous System Viral Diseases/physiopathology , Central Nervous System Viral Diseases/virology , Enterovirus/pathogenicity , Flavivirus/pathogenicity , Herpesviridae/pathogenicity , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/virology , Prion Diseases/physiopathology , Prions/metabolism , Prions/pathogenicity , Simplexvirus/pathogenicity , Virus Diseases/virology , Viruses/pathogenicity , Zika Virus/pathogenicity
17.
J Neurovirol ; 27(5): 667-690, 2021 10.
Article in English | MEDLINE | ID: covidwho-1439770

ABSTRACT

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible disease. SARS-CoV-2 is estimated to have infected over 153 million people and to have caused over 3.2 million global deaths since its emergence in December 2019. SARS-CoV-2 is the seventh coronavirus known to infect humans, and like other coronaviruses, SARS-CoV-2 infection is characterized by a variety of symptoms including general flu-like symptoms such as a fever, sore throat, fatigue, and shortness of breath. Severe cases often display signs of pneumonia, lymphopenia, acute kidney injury, cardiac injury, cytokine storms, lung damage, acute respiratory distress syndrome (ARDS), multiple organ failure, sepsis, and death. There is evidence that around 30% of COVID-19 cases have central nervous system (CNS) or peripheral nervous system (PNS) symptoms along with or in the absence of the previously mentioned symptoms. In cases of CNS/PNS impairments, patients display dizziness, ataxia, seizure, nerve pain, and loss of taste and/or smell. This review highlights the neurological implications of SARS-CoV-2 and provides a comprehensive summary of the research done on SARS-CoV-2 pathology, diagnosis, therapeutics, and vaccines up to May 5.


Subject(s)
COVID-19/complications , Central Nervous System Diseases/virology , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/therapy , Humans , SARS-CoV-2
18.
Brain Res Bull ; 177: 155-163, 2021 12.
Article in English | MEDLINE | ID: covidwho-1433004

ABSTRACT

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its threat to humans have drawn worldwide attention. The acute and long-term effects of SARS-CoV-2 on the nervous system pose major public health challenges. Patients with SARS-CoV-2 present diverse symptoms of the central nervous system. Exploring the mechanism of coronavirus damage to the nervous system is essential for reducing the long-term neurological complications of COVID-19. Despite rapid progress in characterizing SARS-CoV-2, the long-term effects of COVID-19 on the brain remain unclear. The possible mechanisms of SARS-CoV-2 injury to the central nervous system include: 1) direct injury of nerve cells, 2) activation of the immune system and inflammatory cytokines caused by systemic infection, 3) a high affinity of the SARS-CoV-2 spike glycoprotein for the angiotensin-converting enzyme ACE2, 4) cerebrovascular disease caused by hypoxia and coagulation dysfunction, and 5) a systemic inflammatory response that promotes cognitive impairment and neurodegenerative diseases. Although we do not fully understand the mechanism by which SARS-CoV-2 causes nerve injury, we hope to provide a framework by reviewing the clinical manifestations, complications, and possible mechanisms of neurological damage caused by SARS-CoV-2. With hope, this will facilitate the early identification, diagnosis, and treatment of possible neurological sequelae, which could contribute toward improving patient prognosis and preventing transmission.


Subject(s)
COVID-19/complications , Central Nervous System Diseases/virology , Central Nervous System Diseases/pathology , Humans , SARS-CoV-2
20.
Int J Mol Sci ; 22(3)2021 Jan 26.
Article in English | MEDLINE | ID: covidwho-1389389

ABSTRACT

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients' CNS and serve as a platform for therapeutic development and personalized precision medicine.


Subject(s)
Central Nervous System Diseases/drug therapy , Drug Discovery/methods , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Tissue Engineering/methods , Animals , COVID-19/pathology , Central Nervous System Diseases/pathology , Drug Discovery/instrumentation , Drug Evaluation, Preclinical/instrumentation , Drug Evaluation, Preclinical/methods , Humans , Induced Pluripotent Stem Cells/pathology , Lab-On-A-Chip Devices , Organoids/cytology , Organoids/drug effects , Organoids/pathology , Tissue Engineering/instrumentation , Zika Virus Infection/drug therapy , Zika Virus Infection/pathology , COVID-19 Drug Treatment
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