COVID-19-Associated Acute Transverse Myelitis: A Case Series of a Rare Neurologic Condition (original) (raw)
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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.
Brain injury and SARS-CoV-2 infection: Bidirectional pathways
Coronavirus infection disease (COVID-19) is a recent pandemic infectious disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). COVID-19 is associated with different neurological manifestations, as one-third of COVID-19 patients have some neurological disorders, including paraesthesia, headache, cold extremities and disturbances of consciousness, that are more evident in severely affected patients. The entry of SARS-CoV-2 into human host cells is mediated mainly by the cellular receptor angiotensin-converting enzyme 2 (ACE2), which is expressed at very low levels in the CNS under normal conditions. The dissemination of COVID-19 in the systemic circulation or across the cribriform plate of the ethmoid bone during an early or later phase of the infection can lead to cerebral involvement as has been reported in the past for SARS-CoV affected patients. COVID-19-related CNS dysfunction results from direct viral injury, indirect consequences of immune-mediated disease, systemic effects of infection, or local effects of the virus is still a matter of debate and these hypotheses are not mutually exclusive.
Neuropathogenesis of SARS-CoV-2 infection
eLife, 2020
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.
Potential Pathomechanism of Neuro-COVID-19
2020
Gathered data about SARS-CoV-2 have shown strong evidence in terms of neuroinvasive and neurotropic capacities of the virus to reach and cause eventual damage to the Central Nervous System. The spread of the virus may occur through direct and indirect ways, leading to anosmia and/or ageusia. These signs have been observed in many COVID-19 patients and are then included in the diagnostic criteria for Neuro-COVID-19. The invasion of SARS-CoV-2 into the dorsal vagal complex of the brainstem has a harmful impact on the respiratory rhythm, with even respiratory failure. There is evidence that immune response abnormalities including cytokine storm and neuro-inflammation influence not only the disease severity, but also the occurrence of neurological and neurodegenerative manifestations. Many umbrella zones remain unclear about Neuro-COVID-19, which requires more consideration in its clinical, biological and therapeutic aspects and may open new research perspectives.
Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders
European Journal of Medical Research
Background Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood–brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes. Aim The current review aims to prov...
The neuro-invasive potential of SARS-CoV-2; A threat of viral latency
Academia Letters, 2022
The neuro-invasive potential of SARS-CoV-2; A threat of viral latency Fabiha Qayyum Short Communication The neurological manifestations are quite common in SARS-CoV-2 induced COVID-19 disease, which is declared as a global pandemic in December 2019 (1). Neuro-invasion has also been reported commonly in most of the members of the βCoV family i.e., including SARS-CoV (2), MERS-CoV (3), HCoV-229E (4), HCoV-OC43 (5) and porcine hemagglutinating encephalomyelitis coronavirus (HEV) (6). With increasing experience and information regarding SARS-CoV-2 and its growing clinical presentation, the literature review has shown increasing documentation of neurological symptoms of COVID-19 patients (7). A study reported that 36.4% of cases present with neurological manifestations caused by COVID-19 disease (8). COVID-19 patients were observed to show symptoms of encephalitis including sudden olfactory and gustatory instability (10-70%), headache (13%), attention deficit (8-15%), giddiness (17%), neuralgia (2%), audiovisual hallucinations, mental confusion, post-intensive care dysexecutive ailments (36%), tonic-clonic epileptic seizures (1%), motor ataxia (1%), abrupt neurological deficits including respiratory depression (3%) or signs of the pyramidal tract (67%) (9). Two portals of entry have been documented in literature which was mainly opted by SARS-CoV-2 for an invasion in the central nervous system (CNS) (10). One is hematogenous and the other is via the neuronal retrograde route (10). Angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4) receptor is the main culprit of hematogenous spread (11). The SARS-CoV-2 virus binds to the ACE-2 receptor, with its viral spike protein to penetrate the
A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View
Molecular Neurobiology
There is increasing evidence of neurological manifestations and complications in patients with coronavirus disease 19 (COVID-19). More than one-quarter of patients with COVID-19 developed various neurological symptoms, ranging from headache and dizziness to more serious medical conditions, such as seizures and stroke. The recent investigations introduced hyposmia as a potential early criterion of infection with COVID-19. Despite the high mortality and morbidity rate of COVID-19, its exact mechanism of action and pathogenesis is not well characterized. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells. In the present study, we reviewed the most common neurological manifestations and complications that emerged after infection with the SARS-CoV-2 and discussed their possible relation to the expression and function of ACE2. Comprehensive and detailed studies are required to uncover how this virus invades the neural system as well as other critical organs.
Experimental Brain Research
The devastating COVID-19 pandemic is caused by the SARS-CoV-2 virus. It primarily affects the lung and induces acute respiratory distress leading to a decrease in oxygen supply to the cells. This lung insufficiency caused by SARS-CoV-2 virus contributes to hypoxia which can affect the brain and other organ systems. The heightened cytokine storm in COVID-19 patients leads to an immune reaction in the vascular endothelial cells that compromise the host defenses against the SARS-CoV-2 virus in various organs. The vascular endothelial cell membrane breach allows access for SARS-CoV-2 to infect multiple tissues and organs. The neurotropism of spike protein in SARS-CoV-2 rendered by furin site insertion may increase neuronal infections. These could result in encephalitis and encephalopathy. The COVID-19 patients suffered severe lung deficiency often showed effects in the brain and neural system. The early symptoms include headache, loss of smell, mental confusion, psychiatric disorders and strokes, and rarely encephalitis, which indicated the vulnerability of the nervous system to SARS-CoV-2. Infection of the brain and peripheral nervous system can lead to the dysfunction of other organs and result in multi-organ failure. This review focuses on discussing the vulnerability of the nervous system based on the pattern of expression of the receptors for the SARS-CoV-2 and the mechanisms of its cell invasion. The SARS-CoV-2 elicited immune response and host immune response evasion are further discussed. Then the effects on the nervous system and its consequences on neuro-sensory functions are discussed. Finally, the emerging information on the overall genetic susceptibility seen in COVID-19 patients and its implications for therapy outlook is discussed.
SARS-CoV-2 Dissemination Through Peripheral Nerves Explains Multiple Organ Injury
Frontiers in Cellular Neuroscience, 2020
Coronavirus disease (CoVID-19), caused by recently identified severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2), is characterized by inconsistent clinical presentations. While many infected individuals remain asymptomatic or show mild respiratory symptoms, others develop severe pneumonia or even respiratory distress syndrome. SARS-CoV-2 is reported to be able to infect the lungs, the intestines, blood vessels, the bile ducts, the conjunctiva, macrophages, T lymphocytes, the heart, liver, kidneys, and brain. More than a third of cases displayed neurological involvement, and many severely ill patients developed multiple organ infection and injury. However, less than 1% of patients had a detectable level of SARS-CoV-2 in the blood, raising a question of how the virus spreads throughout the body. We propose that nerve terminals in the orofacial mucosa, eyes, and olfactory neuroepithelium act as entry points for the brain invasion, allowing SARS-CoV-2 to infect the brainstem. By exploiting the subcellular membrane compartments of infected cells, a feature common to all coronaviruses, SARS-CoV-2 is capable to disseminate from the brain to periphery via vesicular axonal transport and passive diffusion through axonal endoplasmic reticula, causing multiple organ injury independently of an underlying respiratory infection. The proposed model clarifies a wide range of clinically observed phenomena in CoVID-19 patients, such as neurological symptoms unassociated with lung pathology, protracted presence of the virus in samples obtained from recovered patients, exaggerated immune response, and multiple organ failure in severe cases with variable course and dynamics of the disease. We believe that this model can provide novel insights into CoVID-19 and its long-term sequelae, and establish a framework for further research.