Neurological Manifestation of COVID-19: Current Knowledge on Pathophysiology, Clinical Manifestation and Management

A special issue of Clinical and Translational Neuroscience (ISSN 2514-183X).

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 25694

Special Issue Editors


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Guest Editor
Department of Neurology, Inselspital, University of Bern, Bern, Switzerland
Interests: clinical neurology; stroke; epilepsy; neuroimaging

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Guest Editor
Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria
Interests: Guillain‐Barré syndrome; neurology; neurocritical care

Special Issue Information

Dear Colleagues,

Within the first weeks of the outbreak of the COVID-19 pandemic, reports about neurological manifestations and complications of the disease had already emerged. Smell and taste disorders and prolonged encephalopathy syndromes were among the first manifestations to be described. Since then, multiple neurological manifestations of COVID-19 have been identified, including extra CNS manifestations. The EAN launched one of the first international registries to improve knowledge on neurological complications but also long-term manifestations, and a prevalence of neurological complications between 20% and 60%, depending on the study population, has been found. Given the enormous number of confirmed cases (127,349,248 according to the WHO as of 31 March 2021), even if only 20% of those infected with COVID-19 exhibit neurological symptoms, the worldwide impact will be indescribable. Only a few studies have addressed the pathophysiological pathways of neurological COVID-19 manifestations; accordingly, many questions remain open. Similarly, the potential neurological complications of COVID-19 vaccination are of interest.

In this Special Issue of CTN, we aim to discuss the current knowledge on epidemiology, pathophysiology, and therapeutic options of acute and long-term neurological manifestations in COVID-19 and the vaccines against it.

Prof. Dr. Simon Jung
Prof. Dr. Raimund Helbok
Guest Editors

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Keywords

  • COVID-19
  • neurological manifestation
  • long-term effects
  • smell disorder
  • imaging manifestations
  • Guillain–Barré syndrome

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Published Papers (7 papers)

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Editorial

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2 pages, 174 KiB  
Editorial
Neurological Manifestation of COVID-19: Current Knowledge on Pathophysiology, Clinical Manifestation and Management
by Simon Jung
Clin. Transl. Neurosci. 2022, 6(3), 19; https://doi.org/10.3390/ctn6030019 - 22 Jul 2022
Viewed by 1846
Abstract
Within the first few weeks of the outbreak of the COVID-19 pandemic, reports about the neurological manifestations and complications of the disease had already emerged [...] Full article

Research

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25 pages, 1912 KiB  
Article
Long COVID Neuropsychological Deficits after Severe, Moderate, or Mild Infection
by Philippe Voruz, Gilles Allali, Lamyae Benzakour, Anthony Nuber-Champier, Marine Thomasson, Isabele Jacot de Alcântara, Jordan Pierce, Patrice H. Lalive, Karl-Olof Lövblad, Olivia Braillard, Matteo Coen, Jacques Serratrice, Jérôme Pugin, Radek Ptak, Idris Guessous, Basile N. Landis, Frédéric Assal and Julie A. Péron
Clin. Transl. Neurosci. 2022, 6(2), 9; https://doi.org/10.3390/ctn6020009 - 29 Mar 2022
Cited by 38 | Viewed by 7681
Abstract
There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, even in its mild or moderate respiratory forms, can include long-term neuropsychological deficits. Standardized neuropsychological, psychiatric, neurological, and olfactory tests were administered to 45 patients 236.51 ± 22.54 days after [...] Read more.
There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, even in its mild or moderate respiratory forms, can include long-term neuropsychological deficits. Standardized neuropsychological, psychiatric, neurological, and olfactory tests were administered to 45 patients 236.51 ± 22.54 days after hospital discharge following severe, moderate, or mild respiratory severity from SARS-CoV-2 infection (severe = intensive care unit hospitalization, moderate = conventional hospitalization, mild = no hospitalization). Deficits were found in all domains of cognition, and the prevalence of psychiatric symptoms was relatively high in the three groups. The severe infection group performed more poorly on long-term episodic memory tests and exhibited greater anosognosia than did the other two groups. Those with moderate infection had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. Individuals with mild infection were more stressed, anxious, and depressed. The data support the hypothesis that the virus targets the central nervous system (notably the limbic system) and the notion that there are different neuropsychological phenotypes. Full article
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6 pages, 335 KiB  
Article
COVID-19 in a Neuroimmunological Outpatient Cohort: The Bernese Experience
by Maximilian Pistor, Anke Salmen, Andrew Chan and Robert Hoepner
Clin. Transl. Neurosci. 2022, 6(1), 6; https://doi.org/10.3390/ctn6010006 - 16 Feb 2022
Viewed by 2935
Abstract
The COVID-19 pandemic specifically affects the management and treatment of patients with autoimmune neurological disorders. Major concerns include potentially higher risks of infection or severe disease course under certain immunotherapies used to treat those disorders and the influence of COVID-19 on the underlying [...] Read more.
The COVID-19 pandemic specifically affects the management and treatment of patients with autoimmune neurological disorders. Major concerns include potentially higher risks of infection or severe disease course under certain immunotherapies used to treat those disorders and the influence of COVID-19 on the underlying disease. We present data of the neuroimmunological outpatient department of the University Hospital of Bern (Switzerland). 24 cases were analyzed, 19 of them suffered from Multiple Sclerosis. Of these 24 patients, 6 were hospitalized, 2/6 were treated in the Intensive Care Unit. Possible risk factors for severe course (defined as need for hospitalization) observed in our cohort included cardiovascular risk factors, treatment with B-cell depleting agents, Sphingosine-1 Phosphate Receptor Modulators, and oral steroid therapies. These data are based on a small, retrospective observational cohort and should be interpreted with caution, although they are in line with several other cohort studies. Full article
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Review

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9 pages, 508 KiB  
Review
Cerebral Venous Sinus Thrombosis Associated with Vaccine-Induced Thrombotic Thrombocytopenia—A Narrative Review
by Adrian Scutelnic, Justine Brodard, Johanna A. Kremer Hovinga, Marcel Arnold and Mirjam R. Heldner
Clin. Transl. Neurosci. 2022, 6(2), 11; https://doi.org/10.3390/ctn6020011 - 11 Apr 2022
Viewed by 2775
Abstract
In March 2021, cerebral venous sinus thrombosis and thrombocytopenia after vaccination with adenovirus-based vaccine against SARS-CoV-2 were first reported. The underlining condition has been termed vaccine-induced immune thrombocytopenia (VITT). Anti-platelet factor 4 antibodies have been proposed as a central component of the pathomechanism. [...] Read more.
In March 2021, cerebral venous sinus thrombosis and thrombocytopenia after vaccination with adenovirus-based vaccine against SARS-CoV-2 were first reported. The underlining condition has been termed vaccine-induced immune thrombocytopenia (VITT). Anti-platelet factor 4 antibodies have been proposed as a central component of the pathomechanism. Treatment recommendations entailed immunomodulation with intravenous immunoglobulins, avoidance of heparins and avoidance of platelet transfusions. Although mortality from VITT-associated cerebral venous sinus thrombosis has decreased over time, it remains high. The aim of this narrative review is to describe different aspects of this disease according to the current state of knowledge. Full article
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6 pages, 1055 KiB  
Review
NeuroCOVID: Insights into Neuroinvasion and Pathophysiology
by Jakob Matschke, Susanne Krasemann, Hermann C. Altmeppen, Mohsin Shafiq and Markus Glatzel
Clin. Transl. Neurosci. 2022, 6(2), 10; https://doi.org/10.3390/ctn6020010 - 5 Apr 2022
Cited by 1 | Viewed by 3717
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may lead to acute and chronic neurological symptoms (NeuroCOVID-19). SARS-CoV-2 may spread from the respiratory tract to the central nervous system as the central nervous system (CNS) of certain patients [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may lead to acute and chronic neurological symptoms (NeuroCOVID-19). SARS-CoV-2 may spread from the respiratory tract to the central nervous system as the central nervous system (CNS) of certain patients dying from COVID-19 shows virus-related neuropathological changes. Moreover, a syndrome found in many patients having passed a SARS-CoV-2 infection, which is termed long COVID and characterized by lasting fatigue and other diverse clinical features, may well have some of its pathological correlates inside the CNS. Although knowledge on the routes of SARS-CoV-2 neuroinvasion and the pathophysiology of NeuroCOVID have increased, the molecular mechanisms are not yet fully understood. This includes the key question: to understand if observed CNS damage is a direct cause of viral damage or indirectly mediated by an overshooting neuroimmune response. Full article
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7 pages, 277 KiB  
Review
Hot Topics on COVID-19 and Its Possible Association with Guillain-Barré Syndrome
by Anelia Dietmann, Paolo Ripellino, Andrea M. Humm, Thomas Hundsberger, Bettina Schreiner, Marie Théaudin and Olivier Scheidegger
Clin. Transl. Neurosci. 2022, 6(1), 7; https://doi.org/10.3390/ctn6010007 - 15 Mar 2022
Cited by 3 | Viewed by 3295
Abstract
As the COVID-19 pandemic progresses, reports of neurological manifestations are increasing. However, despite a high number of case reports and case series on COVID-19 and Guillain-Barré-Syndrome (GBS), a causal association is still highly debated, due to the lack of case-control studies. In this [...] Read more.
As the COVID-19 pandemic progresses, reports of neurological manifestations are increasing. However, despite a high number of case reports and case series on COVID-19 and Guillain-Barré-Syndrome (GBS), a causal association is still highly debated, due to the lack of case-control studies. In this opinion paper, we focus on a few clinically relevant questions regarding the possible link between GBS and SARS-CoV-2 infection or vaccination based on our personal clinical experience and literature review. Full article

Other

2 pages, 179 KiB  
Case Report
Waning Humoral Immune Response to SARS-CoV-2 Vaccination with Symptomatic Infection after Initiation of Anti-CD20 Treatment in a Patient with Multiple Sclerosis
by Robert Hoepner and Anke Salmen
Clin. Transl. Neurosci. 2022, 6(1), 8; https://doi.org/10.3390/ctn6010008 - 18 Mar 2022
Viewed by 2305
Abstract
Waning humoral responses to SARS-CoV-2 vaccination have been reported arguing for booster vaccinations even in healthy populations. Multiple sclerosis (MS) immunotherapy with anti-CD20 monoclonal antibodies may negatively influence morbidity and mortality of COVID-19. The opportunity to treat patients at risk for a severe [...] Read more.
Waning humoral responses to SARS-CoV-2 vaccination have been reported arguing for booster vaccinations even in healthy populations. Multiple sclerosis (MS) immunotherapy with anti-CD20 monoclonal antibodies may negatively influence morbidity and mortality of COVID-19. The opportunity to treat patients at risk for a severe COVID-19 course with specific monoclonal antibodies targeting SARS-CoV-2 represents an important novel measure for patient safety. We report a patient with waning humoral vaccination response around five months after two mRNA vaccination doses upon initiation of ocrelizumab treatment. Symptomatic COVID-19 infection was treated with casirivimab/imdevimab with rapid symptom recovery. Full article
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