SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

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Elucidating the Neuropathologic Mechanisms of SARS-CoV-2 Infection

Frontiers in Neurology ◽

10.3389/fneur.2021.660087 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mar Pacheco-Herrero ◽

Luis O. Soto-Rojas ◽

Charles R. Harrington ◽

Yazmin M. Flores-Martinez ◽

Marcos M. Villegas-Rojas ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Molecular Mechanisms ◽

Cell Types ◽

Public Health Emergency ◽

Converting Enzyme ◽

Neurological Manifestations ◽

Brain Areas ◽

Angiotensin Converting Enzyme 2 ◽

The Central Nervous System

The current pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency. To date, March 1, 2021, coronavirus disease 2019 (COVID-19) has caused about 114 million accumulated cases and 2.53 million deaths worldwide. Previous pieces of evidence suggest that SARS-CoV-2 may affect the central nervous system (CNS) and cause neurological symptoms in COVID-19 patients. It is also known that angiotensin-converting enzyme-2 (ACE2), the primary receptor for SARS-CoV-2 infection, is expressed in different brain areas and cell types. Thus, it is hypothesized that infection by this virus could generate or exacerbate neuropathological alterations. However, the molecular mechanisms that link COVID-19 disease and nerve damage are unclear. In this review, we describe the routes of SARS-CoV-2 invasion into the central nervous system. We also analyze the neuropathologic mechanisms underlying this viral infection, and their potential relationship with the neurological manifestations described in patients with COVID-19, and the appearance or exacerbation of some neurodegenerative diseases.

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Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Frontiers in Neurology ◽

10.3389/fneur.2020.592888 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lintao Wang ◽

Zhiguang Ren ◽

Li Ma ◽

Yanjie Han ◽

Wenqiang Wei ◽

...

Keyword(s):

Public Health ◽

Central Nervous System ◽

Nervous System ◽

Neurological Diseases ◽

Public Health Problem ◽

Neurological Complications ◽

Major Public Health Problem ◽

The Central Nervous System ◽

The Impact ◽

Great Harm

COVID-19 has spread rapidly worldwide since its outbreak and has now become a major public health problem. More and more evidence indicates that SARS-CoV-2 may not only affect the respiratory system but also cause great harm to the central nervous system. Therefore, it is extremely important to explore in-depth the impact of SARS-CoV-2 infection on the nervous system. In this paper, the possible mechanisms of SARS-CoV-2 invading the central nervous system during COVID-19, and the neurological complications caused by SARS-CoV-2 infection were reviewed.

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Neurological manifestations and complications in patients with covid-19

Translational Medicine ◽

10.18705/2311-4495-2020-7-3-21-29 ◽

2020 ◽

Vol 7 (3) ◽

pp. 21-29

Author(s):

I. K. Ternovyh ◽

M. P. Topuzova ◽

A. D. Chaykovskaya ◽

P. Sh. Isabekova ◽

T. M. Alekseeva

Keyword(s):

Nervous System ◽

Neurological Diseases ◽

Neurological Complications ◽

Epidemiological Studies ◽

Neurological Manifestations ◽

Long Time ◽

The Central Nervous System ◽

Coronavirus Infection ◽

Mechanisms Of Development ◽

Large Groups

It becomes apparent that the neurological complications of COVID-19 are significantly common, but in some cases, establishing a causal relationship is difficult. For example, a stroke can occur for reasons unrelated to coronavirus infection, while Guillain–Barré syndrome and meningoencephalitis are likely to be a parainfection. Only long-term epidemiological studies in large groups of patients can clarify some of these issues. This will help to better understand the mechanisms of development of complications and develop schemes for their treatment and subsequent rehabilitation. The article presents the mechanisms of penetration of the coronavirus into the nervous system and systematizes the neurological manifestations and complications of COVID-19, which were described in the first 3 months of the pandemic. Particular attention is paid to the consideration of the complications of COVID-19 from the central and peripheral nervous system, the most interesting clinical examples are considered. Summing up the analysis of the literature, we can say that the clinical picture of neurological diseases and syndromes caused by coronavirus infection corresponds to the usual notions. Also considered is the assumption that SARS-CoV-2 can persist for a long time in the central nervous system in the form of inactive fragments, which means that it can recur in predisposed individuals when appropriate conditions arise. This suggestion is alarming regarding distant neurological complications in infected and cured patients.

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Neurological complications and COVID-19: A literature review

NeuroPharmac Journal ◽

10.37881/1.611 ◽

2021 ◽

pp. 142-144

Author(s):

Aslam Pathan

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Early Diagnosis ◽

Healthcare Workers ◽

Altered Mental Status ◽

Neurological Complications ◽

Review Article ◽

Impaired Consciousness ◽

Wide Range ◽

The Central Nervous System

Reported studies from many works of literature state that coronavirus disease 2019 (COVID-19) affects the central nervous system and peripheral nervous system leads to many neurological indications including headache, dizziness, impaired consciousness, acute cerebrovascular disease, epilepsy, hyposmia/anosmia, hypogeusia/ageusia, muscle pain, altered mental status, and Guillain- Barre syndrome. This review article summarized the reported neurological complications in coronavirus disease 2019 patients worldwide. Healthcare workers should aware of a wide range of neurological symptoms for the early diagnosis and management of the cases.

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Divided mind – divided brain. The neurobiology of dissociative identity disorder from the perspective of dynamical systems theory

Psychiatria i Psychologia Kliniczna ◽

10.15557/pipk.2021.0003 ◽

2021 ◽

Vol 21 (1) ◽

pp. 27-35

Author(s):

Jakub Skałbania ◽

Karolina Polewik ◽

Igor J. Pietkiewicz ◽

Radosław Tomalski

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Dynamical Systems ◽

Systems Theory ◽

Dissociative Identity Disorder ◽

Dynamical Systems Theory ◽

Clinical Aspects ◽

Wide Range ◽

The Central Nervous System ◽

The Impact

Explaining the biology of dissociative identity disorder and its clinical aspects is one of the major challenges in modern neuroscience. The complexity and the unique nature of this disorder, coupled with insufficient biopsychological models needed for creating universal therapeutic procedures, make the treatment difficult. The vast majority of neuroimaging studies in dissociative identity disorder patients proved to be inconclusive. Abnormalities of particular brain structures do not explain the wide range of symptoms in dissociative identity disorder. Moreover, the findings are partly contradictory. Collecting adequate representative study samples is difficult and most reports are in fact single case studies. On top of that, meta-analyses show that patients with dissociative identity disorder usually present with additional mental problems, which makes interpretation of neuroimaging data extremely difficult. Nowadays, scientific research on dissociative identity disorder focuses on child trauma and its influence on the development of the central nervous system. This article is an overview of recent research on the neurobiology of dissociative identity disorder, with particular emphasis on the impact of childhood trauma on the development of the central nervous system. It focuses on hypotheses attempting to capture the specific dynamics of neural activity leading to neural network fragmentation, and uses the dynamical systems theory to describe this phenomenon.

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Overview of COVID-19 and neurological complications

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0116 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Nasrin Hosseini ◽

Shabnam Nadjafi ◽

Behnaz Ashtary

Keyword(s):

Nervous System ◽

Severe Acute Respiratory Syndrome ◽

Cranial Nerve ◽

Virus Disease ◽

Neurological Complications ◽

The Body ◽

Neurological Manifestations ◽

Wide Range ◽

The World ◽

Symptoms And Signs

Abstract The sudden and storming onset of coronavirus 2 infection (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) was associated by severe acute respiratory syndrome. Recently, corona virus disease 19 (COVID-19) has appeared as a pandemic throughout the world. The mutational nature of the virus, along with the different means of entering and spreading throughout the body has involved different organs. Thus, patients are faced with a wide range of symptoms and signs. Neurological symptoms, such as anosmia, agnosia, stroke, paralysis, cranial nerve deficits, encephalopathy, meningitis, delirium and seizures, are reported as common complications affecting the course of the disease and its treatment. In this review, special attention was paid to reports that addressed the acute or chronic neurological manifestations in COVID-19 patients who may present acute respiratory syndrome or not. Moreover, we discussed the central (CNS) and peripheral nervous system (PNS) complications in SARS-Cov2-infected patients, and also the pathophysiology of neurological abnormalities in COVID-19.

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Demyelinating solitary lesion of the central nervous system associated with COVID-19: a case report and literature review

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20204998 ◽

2020 ◽

Vol 7 (12) ◽

pp. 1884

Author(s):

Mohammed Alqwaifly

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neurological Complications ◽

Neurological Manifestations ◽

Solitary Lesion ◽

Altered Level ◽

Cerebrovascular Complications ◽

The Central Nervous System ◽

1918 Influenza ◽

Novel Coronavirus

In December 2019, coronavirus disease (COVID-19) emerged in China and rapidly spread to the world to become the largest pandemic since the 1918 influenza. The disease has been identified as a severe acute respiratory syndrome caused by a novel coronavirus-2 (SARS-CoV-2). Although the typical presentation is respiratory symptoms, reports of neurological involvements are increasing, as more than one-third of patients with COVID-19 develop neurological manifestations. The most frequently reported neurological manifestations in COVID-19 patients were headache, dizziness, taste, and smell impairments, and altered level of consciousness. More specific neurological complications were also reported in literature including acute cerebrovascular complications, seizures, meningoencephalitis, and Guillain-Barré syndrome. Very few studies have shown CNS demyelinating lesions as complications of COVID-19. Current report described a case of a COVID-19 patient with an acute solitary demyelinating lesion in the central nervous system. I also reviewed and summarized the available related cases.

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Are we sure that the neurological impact of COVID 19 in childhood has not been underestimated?

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01144-y ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Nicola Principi ◽

Susanna Esposito

Keyword(s):

Nervous System ◽

Pediatric Patients ◽

Signs And Symptoms ◽

Complete Recovery ◽

Underlying Disease ◽

Neurological Complications ◽

Neurological Manifestations ◽

Increased Risk ◽

The Central Nervous System ◽

Almost All

Abstract Background Presently, it is known that, even if less frequently than in adults, children can develop a severe new coronavirus disease 2019 (COVID-19). Children with the SARS-CoV-2 infection can have neurological signs and symptoms of disease more frequently than previously thought, revealing the involvement of the central nervous system, the peripheral nervous system, or both. Aim of this manuscript is to highlight the neurologic complications associated with SARS-CoV-2 among pediatric patients with COVID-19, suggesting when to monitor carefully neurologic development. Main findings Children with a severe chronic underlying disease, infants and toddlers and those who develop the so-called multisystem inflammatory syndrome (MIS-C) are those with the highest incidence of neurological complications. Fortunately, in most of the cases, neurological manifestations, mainly represented by headache and anosmia, are mild and transient and do not significantly complicate the COVID-19 course. However, in some cases, very severe clinical problems associated with relevant alterations of neuroimaging, electroencephalography, nerve conduction studies and electromyography findings can develop. Generally, almost all the children with COVID-19 and neurological manifestations till now described have made a complete recovery, although in some cases this has occurred after several weeks of treatment. Moreover, COVID-19 infection during pregnancy has been found associated with an increased risk of obstetric complications that can lead to neurological acute and long-term manifestations in neonates. Conclusions Based on data showing the neurologic impact of COVID-19 in pediatric age, we suggest monitoring neurological development a few months after healing in pediatric patients who have presented MIS-C, seizures or other neurological manifestations and in children of pregnant women with COVID-19 in order to detect overt and subtle deficits.

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Neurological symptoms, manifestations, and complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)

Journal of Neurology ◽

10.1007/s00415-021-10406-y ◽

2021 ◽

Author(s):

Biyan Nathanael Harapan ◽

Hyeon Joo Yoo

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Case Reports ◽

Case Series ◽

Altered Mental Status ◽

Neurological Complications ◽

Neurological Symptoms ◽

Neurological Manifestations ◽

Fisher Syndrome ◽

Novel Coronavirus ◽

The Impact

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and was first identified in Wuhan, China in December 2019. It is evident that the COVID-19 pandemic has become a challenging world issue. Although most COVID-19 patients primarily develop respiratory symptoms, an increasing number of neurological symptoms and manifestations associated with COVID-19 have been observed. In this narrative review, we elaborate on proposed neurotropic mechanisms and various neurological symptoms, manifestations, and complications of COVID-19 reported in the present literature. For this purpose, a review of all current published literature (studies, case reports, case series, reviews, editorials, and other articles) was conducted and neurological sequelae of COVID-19 were summarized. Essential and common neurological symptoms including gustatory and olfactory dysfunctions, myalgia, headache, altered mental status, confusion, delirium, and dizziness are presented separately in sections. Moreover, neurological manifestations and complications that are of great concern such as stroke, cerebral (sinus) venous thrombosis, seizures, meningoencephalitis, Guillain–Barré syndrome, Miller Fisher syndrome, acute myelitis, and posterior reversible encephalopathy syndrome (PRES) are also addressed systematically. Future studies that examine the impact of neurological symptoms and manifestations on the course of the disease are needed to further clarify and assess the link between neurological complications and the clinical outcome of patients with COVID-19. To limit long-term consequences, it is crucial that healthcare professionals can early detect possible neurological symptoms and are well versed in the increasingly common neurological manifestations and complications of COVID-19.

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