Covid-19 Neurological Effects are Cytokine-Mediated (original) (raw)
Related papers
Journal of Alzheimer's Disease
Anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with coronavirus disease-19 (COVID-19) which is caused by acute respiratory syndrome coronavirus 2 (SARS-Cov2). There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain. In this article, we review the reports that address neurological manifestations in patients with COVID-19 who may present with acute neurological symptoms (e.g., stroke), even without typical respiratory symptoms such as fever, cough, or shortness of breath. Next, we discuss the different neurobiological processes and mechanisms that may underlie the link between SARS-Cov2 and COVID-19 in the brain, cranial nerves, peripheral nerves, and muscles. Finally, we propose a basic "NeuroCovid" classification scheme that integrates these concepts and highlights some of the short-term challenges for the practice of neurology today and the longterm sequalae of COVID-19 such as depression, OCD, insomnia, cognitive decline, accelerated aging, Parkinson's disease, or Alzheimer's disease in the future. In doing so, we intend to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system.
Neurological Sequelae of COVID-19
Journal of Integrative Neuroscience
Background: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. Objective: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. Methods: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "
Neurological Involvement in COVID-19 and Potential Mechanisms: A Review
Neurocritical Care
As the current understanding of COVID-19 continues to evolve, a synthesis of the literature on the neurological impact of this novel virus may help inform clinical management and highlight potentially important avenues of investigation. Additionally, understanding the potential mechanisms of neurologic injury may guide efforts to better detect and ameliorate these complications. In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis. Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury. We also discuss evidence that suggests that SARS-CoV-2 may be a vasculotropic and neurotropic virus. Early reports suggest COVID-19 may be associated with severe neurologic complications, and several plausible mechanisms exist to account for these observations. A heightened awareness of the potential for neurologic involvement and further investigation into the relevant pathophysiology will be necessary to understand and ultimately mitigate SARS-CoV-2-associated neurologic injury.
Ifemed Journal, 2022
Coronavirus disease 19 (COVID-19) is a highly transmissible viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and has since spread rapidly around the world resulting in a global pandemic t hat has caused millions of deaths. Although primarily a disease of the respiratory tract, the spectrum of pathology in COVID-19 is wide and this has been linked to the ability of the virus to attack several organs of the human body such as the heart, kidney and even the brain. A growing body of evidence shows that neuro-tropism is one common feature of coronaviruses. Neurologic manifestations of COVID-19 are abundant and highly variable involving the central nervous system (dizziness, headache, impaired
Putative mechanism of neurological damage in COVID-19 infection
Acta Neurobiologiae Experimentalis
The recent pandemic of the coronavirus infectious disease 2019 (COVID-19) has affected around 192 countries, and projections have shown that around 40% to 70% of world population could be infected in the next months. COVID-19 is caused by the virus SARS-CoV-2, it enters the cells through the ACE2 receptor (angiotensin converting enzyme 2). It is well known that SARS-CoV-2 could develop mild, moderate, and severe respiratory symptoms that could lead to death. The virus receptor is expressed in different organs such as the lungs, kidney, intestine, and brain, among others. In the lung could cause pneumonia and severe acute respiratory syndrome (SARS). The brain can be directly affected by cellular damage due to viral invasion, which can lead to an inflammatory response, by the decrease in the enzymatic activity of ACE2 that regulates neuroprotective, neuro-immunomodulatory and neutralizing functions of oxidative stress. Another severe damage is hypoxemia in patients that do not receive adequate respiratory support. The neurological symptoms that the patient presents, will depend on factors that condition the expression of ACE2 in the brain such as age and sex, as well as the mechanism of neuronal invasion, the immune response and the general state of the patient. Clinical and histopathological studies have described neurological alterations in human patients with COVID-19. These conditions could have a possible contribution to the morbidity and mortality caused by this disease and may even represent the onset of neurodegenerative activity in recovered patients.
COVID-19 and the central nervous system: What is the interplay?
Neuroscience research notes, 2022
Since the outbreak of COVID-19 in 2019-2020, the highly contiguous disease caused by coronavirus 2 (SARS-CoV-2) spread worldwide in a short life span causing a disastrous effect and nearly 5.8 million deaths until February 2022. This global health crisis caused concerns about the disease's aetiology, epidemiology, and management. Understanding the virus's long-and shortterm consequences on diverse human body organs and systems was one of the scientist's concerns despite the virus' respiratory system principal effect. Thus, after reporting neurological symptoms in approximately one-third of hospitalised patients with COVID-19, demonstrating how COVID-19 infects the central nervous system (CNS), causing neurodegenerative diseases in various patients and how the virus affects CNS function became quintessential. There are various mechanisms for COVID-19 pathophysiology, some implicating the potential virus invasion of the blood-brain barrier (BBB). Trans-synaptic and hematogenous routes are the main routes for the virus to pass through the barrier. Binding to the BBB endothelial cells is causing significant alterations in the permeability and integrity properties of the barrier, which cause an elevation of the incidence rate of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis among COVI-19 patients. COVID-19 patients developed neurological manifestations ranging from mild symptoms to severe diseases such as headache and loss of smell, encephalitis and CNS-mediated respiratory distress. However, encephalitis is not a common complication, and it has a significant mortality rate in severely ill patients due to the hyperactivation of the host immune response. Although more investigations are needed, severe COVID-19 patients are considered at a high risk of neurodegenerative disorder as a long-term consequence of SARS-CoV-2 infection.
The neurological significance of COVID-19: Lesson learn from the pandemic
Interdisciplinary Neurosurgery, 2020
Coronavirus Infectious Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously known as 2019 novel coronavirus) is an emerging and rapidly evolving health issue that has been widespread globally and become a pandemic. The typical symptoms of COVID-19 are: a cough, shortness of breath and a fever; from the initial estimates, about 15% of COVID-19 patients present with severe respiratory symptoms and requires hospitalization and intensive care. Recent accumulated evidences showed that the neurological insults also occurred in patients with COVID-19, ranging from mild headache to severe neurological symptoms. In this review, we summarize the COVID-19 and neurological significance of COVID-19.
Neuroimmunology and Neurological Manifestations of COVID-19
COVID-19, Neuroimmunology and Neural Function
Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the...
2020
IImmunodeficiency and hyperinflammation characterize COVID-19 associated states; thus, repurposing of multiple cytokine and/or anti-cytokine drugs currently being used in other therapeutic areas has been suggested as a potential therapeutic strategy in COVID-19 patients. Clinical trials involving these drugs target the most frequent and life-threatening peripheral consequences of the disease, mainly focusing on lung, heart, and coagulation functions; however, a growing number of reports describe a wide range of COVID-associated neurological manifestations (altogether defined as neuro-COVID) including anosmia, seizures, confusion, stroke, encephalopathy, and paralysis. Notably, the underlying pathophysiological mechanisms for neuro-COVID may also include dysregulation of cytokines/chemokines, deficiencies in the innate immune response, and autoimmunity. This suggests that therapeutic attempts with drugs targeting cytokine-mediated inflammation in peripheral organs could also positively affect neuro-COVID manifestations. As a matter of fact, some of these drugs have also been scrutinized for their potential efficacy in treating neuroinflammatory diseases such as optic neuromyelitis, epilepsy, stroke, and traumatic brain injury, among others. On the other hand, anti-cytokine drugs, by impairing relevant physiological activities exerted by these mediators in the CNS, may also be endowed with significant neurological risk. Therefore, the primary aim of the present manuscript is to review the available preclinical and clinical data regarding the neurological effects of the drugs targeting cytokine-mediated inflammation, in order to raise awareness about their potentially beneficial or detrimental neurological consequences when used to treat COVID-19 patients.