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1.
Ann Neurol ; 91(3): 342-352, 2022 03.
Article in English | MEDLINE | ID: covidwho-1648414

ABSTRACT

OBJECTIVE: The study was undertaken to assess the impact of B cell depletion on humoral and cellular immune responses to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccination in patients with various neuroimmunologic disorders on anti-CD20 therapy. This included an analysis of the T cell vaccine response to the SARS-CoV-2 Delta variant. METHODS: We investigated prospectively humoral and cellular responses to SARS-CoV-2 mRNA vaccination in 82 patients with neuroimmunologic disorders on anti-CD20 therapy and 82 age- and sex-matched healthy controls. For quantification of antibodies, the Elecsys anti-SARS-CoV-2 viral spike (S) immunoassay against the receptor-binding domain (RBD) was used. IFN-gamma enzyme-linked immunosorbent spot assays were performed to assess T cell responses against the SARS-CoV-2 Wuhan strain and the Delta variant. RESULTS: SARS-CoV-2-specific antibodies were found less frequently in patients (70% [57/82]) compared with controls (82/82 [100%], p < 0.001). In patients without detectable B cells (<1 B cell/mcl), seroconversion rates and antibody levels were lower compared to nondepleted (≥1 B cell/mcl) patients (p < 0.001). B cell levels ≥1 cell/mcl were sufficient to induce seroconversion in our cohort of anti-CD20 treated patients. In contrast to the antibody response, the T-cell response against the Wuhan strain and the Delta variant was more pronounced in frequency (p < 0.05) and magnitude (p < 0.01) in B-cell depleted compared to nondepleted patients. INTERPRETATION: Antibody responses to SARS-CoV-2 mRNA vaccinnation can be attained in patients on anti-CD20 therapy by the onset of B cell repopulation. In the absence of B cells, a strong T cell response is generated which may help to protect against severe coronavirus disease 2019 (COVID-19) in this high-risk population. ANN NEUROL 2022;91:342-352.


Subject(s)
Autoimmune Diseases of the Nervous System/immunology , B-Lymphocytes/immunology , COVID-19 Vaccines/administration & dosage , Immunity, Cellular/immunology , Immunity, Humoral/immunology , SARS-CoV-2/immunology , Adult , Autoimmune Diseases of the Nervous System/blood , Autoimmune Diseases of the Nervous System/epidemiology , B-Lymphocytes/metabolism , COVID-19/epidemiology , COVID-19/prevention & control , Cohort Studies , Female , Humans , Male , Middle Aged , Neuroimmunomodulation/immunology , Prospective Studies , SARS-CoV-2/metabolism
2.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1537202

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
3.
J Neuroinflammation ; 18(1): 231, 2021 Oct 13.
Article in English | MEDLINE | ID: covidwho-1468067

ABSTRACT

It is well accepted that environmental stressors experienced over a one's life, from microbial infections to chemical toxicants to even psychological stressors, ultimately shape central nervous system (CNS) functioning but can also contribute to its eventual breakdown. The severity, timing and type of such environmental "hits", woven together with genetic factors, likely determine what CNS outcomes become apparent. This focused review assesses the current COVID-19 pandemic through the lens of a multi-hit framework and disuses how the SARS-COV-2 virus (causative agent) might impact the brain and potentially interact with other environmental insults. What the long-term consequences of SAR2 COV-2 upon neuronal processes is yet unclear, but emerging evidence is suggesting the possibility of microglial or other inflammatory factors as potentially contributing to neurodegenerative illnesses. Finally, it is critical to consider the impact of the virus in the context of the substantial psychosocial stress that has been associated with the global pandemic. Indeed, the loneliness, fear to the future and loss of social support alone has exerted a massive impact upon individuals, especially the vulnerable very young and the elderly. The substantial upswing in depression, anxiety and eating disorders is evidence of this and in the years to come, this might be matched by a similar spike in dementia, as well as motor and cognitive neurodegenerative diseases.


Subject(s)
COVID-19/immunology , Inflammation Mediators/immunology , Mental Disorders/immunology , Neurodegenerative Diseases/immunology , Neuroimmunomodulation/immunology , Animals , Brain/immunology , COVID-19/epidemiology , Humans , Immunotherapy/trends , Mental Disorders/epidemiology , Mental Disorders/therapy , Neurodegenerative Diseases/epidemiology , Neurodegenerative Diseases/therapy , Stress, Psychological/epidemiology , Stress, Psychological/immunology , Stress, Psychological/therapy
4.
Int J Neuropsychopharmacol ; 25(1): 1-12, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1467332

ABSTRACT

From the earliest days of the coronavirus disease 2019 (COVID-19) pandemic, there have been reports of significant neurological and psychological symptoms following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This narrative review is designed to examine the potential psychoneuroendocrine pathogenic mechanisms by which SARS-CoV-2 elicits psychiatric sequelae as well as to posit potential pharmacologic strategies to address and reverse these pathologies. Following a brief overview of neurological and psychological sequelae from previous viral pandemics, we address mechanisms by which SARS-CoV-2 could enter or otherwise elicit changes in the CNS. We then examine the hypothesis that COVID-19-induced psychiatric disorders result from challenges to the neuroendocrine system, in particular the hypothalamic-pituitary-adrenal stress axis and monoamine synthesis, physiological mechanisms that are only further enhanced by the pandemic-induced social environment of fear, isolation, and socioeconomic pressure. Finally, we evaluate several FDA-approved therapeutics in the context of COVID-19-induced psychoneuroendocrine disorders.


Subject(s)
COVID-19/virology , Central Nervous System Viral Diseases/virology , Central Nervous System/virology , Neurosecretory Systems/virology , SARS-CoV-2/pathogenicity , Anti-Inflammatory Agents/therapeutic use , Antidepressive Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/psychology , Central Nervous System/drug effects , Central Nervous System/metabolism , Central Nervous System/physiopathology , Central Nervous System Viral Diseases/drug therapy , Central Nervous System Viral Diseases/physiopathology , Central Nervous System Viral Diseases/psychology , Host-Pathogen Interactions , Humans , Neuroimmunomodulation , Neurosecretory Systems/drug effects , Neurosecretory Systems/metabolism , Neurosecretory Systems/physiopathology , Prognosis , Risk Factors , Virus Internalization
5.
Brain ; 144(12): 3576-3588, 2021 12 31.
Article in English | MEDLINE | ID: covidwho-1358432

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain-Barré syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of CSF and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischaemic injury, blood-brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development and uncovering the underlying disease mechanisms that will guide effective therapies.


Subject(s)
Brain/immunology , COVID-19/epidemiology , COVID-19/immunology , Nervous System Diseases/epidemiology , Nervous System Diseases/immunology , Neuroimmunomodulation/physiology , Blood-Brain Barrier/immunology , Blood-Brain Barrier/pathology , Brain/pathology , COVID-19/complications , COVID-19/diagnostic imaging , Humans , Nervous System Diseases/diagnostic imaging
6.
Neurosci Lett ; 760: 136042, 2021 08 24.
Article in English | MEDLINE | ID: covidwho-1262947

ABSTRACT

The airways are constantly exposed to a multitude of inhaled particles and, as such, require a finely tuned discrimination between harmful or potentially threatening stimuli, and discrete responses to maintain homeostasis. Both the immune and nervous systems have the ability to sense environmental (and internal) signals, to integrate the obtained information and to initiate a protective reaction. Lung immunity and innervation are known to be individually involved in these processes, but it is becoming clear that they can also influence one another via a multitude of complex mechanisms. Here, we specifically describe how sensory innervation affects airways immunity with a focus on pathological conditions such as asthma or infections, describing cellular and molecular mechanisms, and highlighting potentially novel therapeutic targets.


Subject(s)
Asthma/immunology , Neuroimmunomodulation , Respiratory System/immunology , Respiratory Tract Infections/immunology , Sensory Receptor Cells/metabolism , Animals , Disease Models, Animal , Humans , Respiratory System/innervation
7.
J Neuroimmune Pharmacol ; 16(3): 519-530, 2021 09.
Article in English | MEDLINE | ID: covidwho-1283811

ABSTRACT

This brief report collects the program and abstracts of the Society on NeuroImmune Pharmacology (SNIP) COVID-19 Virtual Workshop held on April 9, 2021. The workshop consisted of four symposia: Symposium 1: Molecular approaches to COVID-19 pathogenesis and underlying mechanisms; Symposium 2: Therapeutic and vaccine approaches to COVID-19; Symposium 3: Early Career Investigator talks; and Symposium 4: Diversity and Inclusion SNIP Committee (DISC) program: Well-being and reflections. The workshop also featured four special talks on COVID-19 and funding opportunities from the National Institute on Alcohol Abuse and Alcoholism (NIAAA); COVID-19 and funding opportunities from the National Institute on Drug Abuse (NIDA); opportunities from NIH for early career investigator (ECI) fellows; and neurologic and psychiatric complications of SARS-CoV-2 infection. Presenters included NIH officials, SNIP members, and non-member scientists whose abstracts were submitted and accepted for inclusion in the virtual event hosted by the University of Nebraska Medical Center via Zoom webinar. A special theme issue of SNIP's official journal, the Journal of Neuroimmune Pharmacology (JNIP), will collect select papers from the workshop along with other related manuscripts in a special theme issue titled "Neuroimmune Pharmacology of SARS-CoV-2."


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Education/trends , Neuroimmunomodulation/immunology , Societies, Scientific/trends , Antiviral Agents/administration & dosage , Antiviral Agents/immunology , Education/methods , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/immunology , Neuroimmunomodulation/drug effects
8.
Med Sci Monit ; 27: e932962, 2021 Jun 19.
Article in English | MEDLINE | ID: covidwho-1278722

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of the recent pandemic of coronavirus disease 19 (COVID-19). As the infection spreads, there is increasing evidence of neurological and psychiatric involvement in COVID-19. Headache, impaired consciousness, and olfactory and gustatory dysfunctions are common neurological manifestations described in the literature. Studies demonstrating more specific and more severe neurological involvement such as cerebrovascular insults, encephalitis and Guillain-Barre syndrome are also emerging. Respiratory failure, a significant condition that leads to mortality in COVID-19, is hypothesized to be partly due to brainstem impairment. Notably, some of these neurological complications seem to persist long after infection. This review aims to provide an update on what is currently known about neurological involvement in patients with COVID-19 due to SARS-CoV-2 infection. In this review, we demonstrate invasion routes of SARS-CoV-2, provide evidence to support the neurotropism hypothesis of the virus, and investigate the pathological mechanisms that underlie neurological complications associated with SARS-CoV-2.


Subject(s)
COVID-19/physiopathology , Nervous System Diseases/virology , Ageusia/virology , Anosmia/virology , COVID-19/complications , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/virology , Encephalitis/virology , Headache/physiopathology , Headache/virology , Humans , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Neuroimmunomodulation/physiology , Pandemics , SARS-CoV-2/isolation & purification , Stroke/physiopathology , Stroke/virology
9.
J Alzheimers Dis ; 82(3): 883-898, 2021.
Article in English | MEDLINE | ID: covidwho-1259331

ABSTRACT

Cognitive impairment following SARS-CoV-2 infection is being increasingly recognized as an acute and possibly also long-term sequela of the disease. Direct viral entry as well as systemic mechanisms such as cytokine storm are thought to contribute to neuroinflammation in these patients. Biomarkers of COVID-19-induced cognitive impairment are currently lacking, but there is some limited evidence that SARS-CoV-2 could preferentially target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET. Possible confounders include cognitive impairment due to hypoxia and mechanical ventilation and post-traumatic stress disorder. Conversely, patients already suffering from dementia, as well as their caregivers, have been greatly impacted by the disruption of their care caused by COVID-19. Patients with dementia have experienced worsening of cognitive, behavioral, and psychological symptoms, and the rate of COVID-19-related deaths is disproportionately high among cognitively impaired people. Multiple factors, such as difficulties in remembering and executing safeguarding procedures, age, comorbidities, residing in care homes, and poorer access to hospital standard of care play a role in the increased morbidity and mortality. Non-pharmacological interventions and new technologies have shown a potential for the management of patients with dementia, and for the support of their caregivers.


Subject(s)
Alzheimer Disease , Brain , COVID-19/complications , Cognitive Dysfunction , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Biomarkers/analysis , Brain/diagnostic imaging , Brain/metabolism , Brain/physiopathology , Brain/virology , COVID-19/immunology , COVID-19/psychology , COVID-19/therapy , Cognitive Dysfunction/immunology , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/virology , Comorbidity , Humans , Neuroimaging/methods , Neuroimmunomodulation/immunology , Patient Care , SARS-CoV-2
10.
Psychoneuroendocrinology ; 131: 105295, 2021 09.
Article in English | MEDLINE | ID: covidwho-1253500

ABSTRACT

The majority of COVID-19 survivors experience long-term neuropsychiatric symptoms such as fatigue, sleeping difficulties, depression and anxiety. We propose that neuroimmune cross-talk via inflammatory cytokines such as interleukin-6 (IL-6) could underpin these long-term COVID-19 symptoms. This hypothesis is supported by several lines of research, including population-based cohort and genetic Mendelian Randomisation studies suggesting that inflammation is associated with fatigue and sleeping difficulties, and that IL-6 could represent a possible causal driver for these symptoms. Immune activation following COVID-19 can disrupt T helper 17 (TH17) and regulatory T (Treg) cell responses, affect central learning and emotional processes, and lead to a vicious cycle of inflammation and mitochondrial dysfunction that amplifies the inflammatory process and results in immuno-metabolic constraints on neuronal energy metabolism, with fatigue being the ultimate result. Increased cytokine activity drives this process and could be targeted to interrupt it. Therefore, whether persistent IL-6 dysregulation contributes to COVID-19-related long-term fatigue, sleeping difficulties, depression, and anxiety, and whether targeting IL-6 pathways could be helpful for treatment and prevention of long COVID are important questions that require investigation. This line of research could inform new approaches for treatment and prevention of long-term neuropsychiatric symptoms of COVID-19. Effective treatment and prevention of this condition could also help to stem the anticipated rise in depression and other mental illnesses ensuing this pandemic.


Subject(s)
COVID-19/complications , Interleukin-6/physiology , Mental Disorders/etiology , Animals , Anxiety/epidemiology , Anxiety/etiology , COVID-19/epidemiology , COVID-19/etiology , COVID-19/psychology , Cohort Studies , Depression/epidemiology , Depression/etiology , Fatigue/epidemiology , Fatigue/etiology , Humans , Interleukin-6/metabolism , Interleukin-6/pharmacology , Mental Disorders/epidemiology , Neuroimmunomodulation/drug effects , Neuroimmunomodulation/physiology , SARS-CoV-2/physiology , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/etiology , Survivors/statistics & numerical data
11.
Neuroimmunomodulation ; 28(1): 1-21, 2021.
Article in English | MEDLINE | ID: covidwho-1206095

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has devastating effects on the population worldwide. Given this scenario, the extent of the impact of the disease on more vulnerable individuals, such as pregnant women, is of great concern. Although pregnancy may be a risk factor in respiratory virus infections, there are no considerable differences regarding COVID-19 severity observed between pregnant and nonpregnant women. In these circumstances, an emergent concern is the possibility of neurodevelopmental and neuropsychiatric harm for the offspring of infected mothers. Currently, there is no stronger evidence indicating vertical transmission of SARS-CoV-2; however, the exacerbated inflammatory response observed in the disease could lead to several impairments in the offspring's brain. Furthermore, in the face of historical knowledge on possible long-term consequences for the progeny's brain after infection by viruses, we must consider that this might be another deleterious facet of COVID-19. In light of neuroimmune interactions at the maternal-fetal interface, we review here the possible harmful outcomes to the offspring brains of mothers infected by SARS-CoV-2.


Subject(s)
COVID-19/immunology , Neurodevelopmental Disorders/physiopathology , Neuroimmunomodulation/immunology , Pregnancy Complications, Infectious/immunology , Prenatal Exposure Delayed Effects/physiopathology , COVID-19/metabolism , COVID-19/physiopathology , Cytokine Release Syndrome/immunology , Decidua/immunology , Female , Humans , Immune Tolerance/immunology , Infectious Disease Transmission, Vertical , Neuroimmunomodulation/physiology , Placenta/immunology , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/physiopathology , SARS-CoV-2 , Umbilical Cord/immunology
13.
Nat Rev Neurol ; 17(5): 325, 2021 05.
Article in English | MEDLINE | ID: covidwho-1149722
14.
Nervenarzt ; 92(6): 521-530, 2021 Jun.
Article in German | MEDLINE | ID: covidwho-1116542

ABSTRACT

Many neuroimmunological diseases, such as encephalopathy, encephalitis, myelitis and acute disseminated encephalomyelitis (ADEM) have occurred more frequently after infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which indicates a parainfectious or postinfectious association. The most likely underlying mechanisms include virus-triggered overactivation of the immune system with hyperinflammation and cytokine storm but potentially also the development of specific autoantibodies against central nervous system (CNS) tissue. These were predominantly detected in the cerebrospinal fluid of severely ill coronavirus disease 2019 (COVID-19) patients. In contrast, direct damage after invasion of SARS-CoV­2 into the brain and spinal cord does not seem to play a relevant role. Susceptibility to infection with SARS-CoV­2 in patients with multiple sclerosis, myasthenia or other neuroimmunological diseases including the risk for severe disease courses, is not determined by the administered immunotherapy but by known risk factors, such as age, comorbidities and the disease-related degree of disability. Therefore, immunotherapy in these patients should not be delayed or discontinued. The contribution of neuroimmunological mechanisms to long-term sequelae after survival of a COVID-19 illness, such as fatigue, impairment of memory, sleep dysfunction or anxiety, will require long-term clinical follow-up, preferentially in COVID-19 register studies.


Subject(s)
Brain Diseases , COVID-19 , Encephalitis , Humans , Neuroimmunomodulation , SARS-CoV-2
15.
Front Immunol ; 11: 595342, 2020.
Article in English | MEDLINE | ID: covidwho-1106024

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.


Subject(s)
COVID-19/therapy , Cytokine Release Syndrome/therapy , Neuroimmunomodulation/immunology , Vagus Nerve Stimulation/methods , Vagus Nerve/immunology , Acupuncture , Anti-Inflammatory Agents/pharmacology , Cytokines/blood , Drugs, Chinese Herbal/pharmacology , Humans , Inflammation/therapy , Nicotine/pharmacology , SARS-CoV-2 , Solanaceous Alkaloids/pharmacology
16.
Cytokine Growth Factor Rev ; 58: 1-15, 2021 04.
Article in English | MEDLINE | ID: covidwho-1101169

ABSTRACT

SARS-CoV-2 is a novel coronavirus that severely affects the respiratory system, is the cause of the COVID-19 pandemic, and is projected to result in the deaths of 2 million people worldwide. Recent reports suggest that SARS-CoV-2 also affects the central nervous system along with other organs. COVID-19-associated complications are observed in older people with underlying neurological conditions like stroke, Alzheimer's disease, and Parkinson's disease. Hence, we discuss SARS-CoV-2 viral replication and its inflammation-mediated infection. This review also focuses on COVID-19 associated neurological complications in individuals with those complications as well as other groups of people. Finally, we also briefly discuss the current therapies available to treat patients, as well as ongoing available treatments and vaccines for effective cures with a special focus on the therapeutic potential of a small 5 amino acid peptide (PHSCN), ATN-161, that inhibits SARS-CoV-2 spike protein binding to both integrin α5ß1 and α5ß1/hACE2.


Subject(s)
COVID-19/complications , Nervous System Diseases/virology , Neurogenic Inflammation/virology , SARS-CoV-2/pathogenicity , Age Factors , Aged , Aged, 80 and over , COVID-19/epidemiology , Humans , Nervous System Diseases/epidemiology , Neurogenic Inflammation/complications , Neuroimmunomodulation/physiology , Pandemics
17.
Horm Mol Biol Clin Investig ; 42(1): 69-75, 2021 Feb 23.
Article in English | MEDLINE | ID: covidwho-1094095

ABSTRACT

COVID-19 caused by SARS CoV2 (The novel corona virus) has already taken lives of many people across the globe even more than anyone could have imagined. This outbreak occurred in China and since then it is expanding its devastating effects by leaps and bounds. Initially it appeared to be an outbreak of pneumonia but soon it was found to be much more than that and the infectivity was found to be very high. This is the reason that it has taken whole globe in its trap and become a pandemic in such a short span of time. Death is occurring because it is a new virus and human body has no specific antibodies for it. Presently there is no approved vaccine so everyone is susceptible but people with co-morbidities appear to be in more risk and the best way for protection is social distancing and increasing one's natural immunity by taking healthy diet and exercise. When a person is infected the clinical presentation ranges from asymptomatic to severe ARDS, sudden onset of anosmia, headache, cough may be the initial symptoms. This review is focused on immunopathology and effect of COVID-19 on neurological disorders and also the neurological manifestations and the treatment.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Nervous System Diseases , Pandemics , COVID-19/immunology , COVID-19/therapy , Comorbidity , Humans , Immune System/physiology , Nervous System Diseases/complications , Nervous System Diseases/epidemiology , Nervous System Diseases/immunology , Nervous System Diseases/therapy , Neuroimmunomodulation/physiology , SARS-CoV-2/immunology , SARS-CoV-2/physiology
18.
J Neurovirol ; 27(2): 197-216, 2021 04.
Article in English | MEDLINE | ID: covidwho-1080993

ABSTRACT

The pandemic caused by SARS-CoV-2 has caused widespread infection and significant mortality across the globe. Combined virology perspective of SARS-CoV-2 with a deep-rooted understanding of pathophysiological and immunological processes underlying the clinical manifestations of COVID-19 is of prime importance. The characteristic symptom of COVID-19 is respiratory distress with diffused alveolar damage, but emerging evidence suggests COVID-19 might also have neurologic consequences. Dysregulated homeostasis in the lungs has proven to be fatal, but one cannot ignore that the inability to breathe might be due to defects in the respiratory control center of the brainstem. While the mechanism of pulmonary distress has been documented in the literature, awareness of neurological features and their pathophysiology is still in the nascent state. This review makes references to the neuro-immune axis and neuro-invasive potential of SARS-CoV and SARS-CoV2, as well as the prototypic H-CoV strains in human brains. Simultaneously, considerable discussion on relevant experimental evidence of mild to severe neurological manifestations of fellow neurotropic murine-ß-CoVs (m-CoVs) in the mouse model will help understand the underpinning mechanisms of Neuro-COVID. In this review, we have highlighted the neuroimmunopathological processes in murine CoVs. While MHV infection in mice and SARS-CoV-2 infection in humans share numerous parallels, there are critical differences in viral recognition and viral entry. These similarities are highlighted in this review, while differences have also been emphasized. Though CoV-2 Spike does not favorably interact with murine ACE2 receptor, modification of murine SARS-CoV2 binding domain or development of transgenic ACE-2 knock-in mice might help in mediating consequential infection and understanding human CoV2 pathogenesis in murine models. While a global animal model that can replicate all aspects of the human disease remains elusive, prior insights and further experiments with fellow m-ß-CoV-induced cause-effect experimental models and current human COVID-19 patients data may help to mitigate the SARS-CoV-2-induced multifactorial multi-organ failure.


Subject(s)
COVID-19/pathology , Disease Models, Animal , Murine hepatitis virus/pathogenicity , Neuroimmunomodulation/physiology , Animals , COVID-19/immunology , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Humans , Mice , Murine hepatitis virus/immunology , SARS-CoV-2
20.
Mol Psychiatry ; 26(4): 1044-1059, 2021 04.
Article in English | MEDLINE | ID: covidwho-983662

ABSTRACT

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called "cytokine storm". Both pro-inflammatory factors and viruses may cross the blood-brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson's and Alzheimer's disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.


Subject(s)
Brain Diseases/complications , Brain Diseases/pathology , COVID-19/complications , COVID-19/pathology , Neuroimmunomodulation , Receptors, Purinergic P2X7/metabolism , SARS-CoV-2/pathogenicity , Brain Diseases/drug therapy , Brain Diseases/metabolism , COVID-19/immunology , COVID-19/metabolism , Humans , Inflammasomes/immunology , Inflammasomes/metabolism , Pandemics , SARS-CoV-2/immunology
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