Neurological aspects of COVID-19

The coronavirus disease COVID-19 began to spread worldwide in December 2019 from the city of Wuhan (China). COVID-19 is often accompanied by fever, hypoxemic respiratory failure and systemic complications (for example, gastrointestinal, renal, cardiac, neurological, and hepatic lesions), thrombotic phenomena. Central nervous system damage is caused by the primary effect on it, direct neuroinvasion of the virus, and more often by secondary effect due to systemic hyperinflammation. Neurological manifestations include fatigue, headache, insomnia, and olfactory/taste disorders. Neurological manifestations and complications of COVID-19 are diverse: (1) cerebral circulatory disorders, including ischemic stroke and macro/microhemorrhages; (2) encephalopathy; (3) para/postinfectious autoimmune complications, such as GuillainBarre syndrome; (4) meningoencephalitis; (5) neuropsychiatric complications (psychosis and mood disorders). In terms of pathogenesis, neurological disorders in COVID-19 can be caused by neurotropicity and neurovirulence of SARS-CoV-2, cytokine storm, hypoxemia, homeostasis disorders, as well as their combined effects. COVID-19 adversely affects the course and prognosis of chronic neurological disorders in comorbid patients. The review highlights the need for vigilance to early neurological complications in patients infected with SARS-CoV-2 and other coronaviruses, especially since some neurological complications may precede respiratory manifestations.

Download Full-text

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

Antioxidants ◽

10.3390/antiox10060971 ◽

2021 ◽

Vol 10 (6) ◽

pp. 971

Author(s):

Noemí Cárdenas-Rodríguez ◽

Cindy Bandala ◽

América Vanoye-Carlo ◽

Iván Ignacio-Mejía ◽

Saúl Gómez-Manzo ◽

...

Keyword(s):

Neuromuscular Junctions ◽

Cardiac Injury ◽

Clinical Manifestations ◽

Specific Treatment ◽

Kidney Injury ◽

Neurological Complications ◽

Neurological Manifestations ◽

Systemic Complications ◽

The Central Nervous System ◽

Brain Tissue Damage

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an emergent infectious disease that has caused millions of deaths throughout the world. COVID-19 infection’s main symptoms are fever, cough, fatigue, and neurological manifestations such as headache, myalgias, anosmia, ageusia, impaired consciousness, seizures, and even neuromuscular junctions’ disorders. In addition, it is known that this disease causes a series of systemic complications such as adverse respiratory distress syndrome, cardiac injury, acute kidney injury, and liver dysfunction. Due to the neurological symptoms associated with COVID-19, damage in the central nervous system has been suggested as well as the neuroinvasive potential of SARS-CoV-2. It is known that CoV infections are associated with an inflammation process related to the imbalance of the antioxidant system; cellular changes caused by oxidative stress contribute to brain tissue damage. Although anti-COVID-19 vaccines are under development, there is no specific treatment for COVID-19 and its clinical manifestations and complications; only supportive treatments with immunomodulators, anti-vascular endothelial growth factors, modulating drugs, statins, or nutritional supplements have been used. In the present work, we analyzed the potential of antioxidants as adjuvants for the treatment of COVID-19 and specifically their possible role in preventing or decreasing the neurological manifestations and neurological complications present in the disease.

Download Full-text

Neurological manifestations of coronavirus infections: a systematic review

10.1101/2020.08.26.20182196 ◽

2020 ◽

Author(s):

Jesper Almqvist ◽

Tobias Granberg ◽

Antonios Tzortzakakis ◽

Stefanos Klironomos ◽

Evangelia Kollia ◽

...

Keyword(s):

Systematic Review ◽

Cerebrovascular Disorders ◽

Acute Disseminated Encephalomyelitis ◽

Neurological Complications ◽

Diagnostic Workup ◽

Neurological Manifestations ◽

Chronic Disability ◽

Neuropsychiatric Complications ◽

Immune Mediated ◽

Depth Analysis

In order to optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until July 26h 2020) using systematic searches in PubMed, Web of Science and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in-depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS-CoV-2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV-229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)-CoV, SARS-CoV-1 and SARS-CoV-2). Moreover, there are similarities in symptomatology across different HCoVs, particularly between SARS-CoV-1 and SARS-CoV-2. Common neurological manifestations include fatigue, headache and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro-hemorrhages, (2) encephalopathies, (3) para-/postinfectious immune-mediated complications such as Guillain-Barre syndrome and acute disseminated encephalomyelitis, (4) (meningo-)encephalitis, potentially with concomitant seizures and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS-CoV-2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs.

Download Full-text

Neurological complications in patients with SARS-CoV-2 infection: a systematic review

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20200051 ◽

2020 ◽

Vol 78 (5) ◽

pp. 290-300 ◽

Cited By ~ 13

Author(s):

Renato Puppi MUNHOZ ◽

José Luiz PEDROSO ◽

Fábio Augusto NASCIMENTO ◽

Sergio Monteiro de ALMEIDA ◽

Orlando Graziani Povoas BARSOTTINI ◽

...

Keyword(s):

Systematic Review ◽

Literature Search ◽

Neurological Complications ◽

Cerebrovascular Diseases ◽

Neurologic Manifestations ◽

Neurological Manifestations ◽

Systemic Complications ◽

Life Threatening ◽

Critical Patients ◽

Specific Symptoms

ABSTRACT Background: As the COVID-19 pandemic unfolds worldwide, different forms of reports have described its neurologic manifestations. Objective: To review the literature on neurological complications of SARS-CoV-2 infection. Methods: Literature search performed following systematic reviews guidelines, using specific keywords based on the COVID-19 neurological complications described up to May 10th, 2020. Results: A total of 43 articles were selected, including data ranging from common, non-specific symptoms, such as hyposmia and myalgia, to more complex and life-threatening conditions, such as cerebrovascular diseases, encephalopathies, and Guillain-Barré syndrome. Conclusion: Recognition of neurological manifestations of SARS-CoV-2 should be emphasized despite the obvious challenges faced by clinicians caring for critical patients who are often sedated and presenting other concurrent systemic complications.

Download Full-text

Neurological manifestations due to, during and after COVID-19

10.17727/jmsr.2020/8s1-10 ◽

2020 ◽

Vol 8 (S1) ◽

pp. 81-89

Author(s):

Patil A ◽

Mohandas S

Keyword(s):

Early Recognition ◽

Systemic Infection ◽

Neurological Complications ◽

Health Care Facilities ◽

Severe Illness ◽

Atypical Pneumonia ◽

Neurological Manifestations ◽

Systemic Complications ◽

Systemic Symptoms ◽

The Impact

With the ongoing pandemic of coronavirus disease 2019 (COVID-19), many neurological manifestations have been linked to what began as an outbreak of atypical pneumonia. Like other corona viruses, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has potential for neurotropism. Viral invasion and likely pathogenecity has been associated with expression of ACE-2 receptors along endothelia and olfactory mucosa. Hyperinflammatory response after systemic infection is in part responsible for the severity and multi-organ dysfunction seen in severe cases. Features like encephalitis, central and peripheral demyelinating disorders, cranial neuropathies, stroke are seen not only in patients with severe illness but at times preceding any systemic symptoms. Neurological disorders are not only part of acute illness phase but also seen in postinfectious phase likely due to immune mediated effect. Also, long term sequelae in patients with moderate to severe COVID-19, either due to systemic complications or direct virus mediated effect are a matter of concern. High suspicion and early recognition of possible presenting features and neurological complications in severely affected patients is key for management. With the rapidity and enormity of ongoing pandemic whether these observations are causal or casual is yet to be determined. Further collaborations for comparisons of observations across the world in necessary to understand the potential impact of COVID-19. Accessing these observations will help in better understanding the agent host and environmental factors determining the expected impact of this pandemic. Reorganizing health care facilities to apt for better handling COVID-19 over time to come will help to mitigate the impact. Keywords: COVID-19; neurological manifestations; encephalitis; stroke; neurotropism

Download Full-text

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

International Journal of Molecular Sciences ◽

10.3390/ijms21155475 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5475 ◽

Cited By ~ 11

Author(s):

Manuela Pennisi ◽

Giuseppe Lanza ◽

Luca Falzone ◽

Francesco Fisicaro ◽

Raffaele Ferri ◽

...

Keyword(s):

Nervous System ◽

Molecular Mechanisms ◽

Neuronal Damage ◽

Neurological Complications ◽

Neurological Manifestations ◽

Wide Range ◽

Inflammatory State ◽

Acute Polyneuropathy ◽

The Central Nervous System ◽

The Impact

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.

Download Full-text

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.

Download Full-text

Concrescence of the cervical vertebrae and neurological complications

Vestnik nevrologii, psihiatrii i nejrohirurgii (Bulletin of Neurology, Psychiatry and Neurosurgery) ◽

10.33920/med-01-2103-03 ◽

2021 ◽

pp. 195-201

Author(s):

Sabiyat Abdulaevna Yakhyaeva ◽

Naida Isagadzhievna Garabova ◽

Madina Garunovna Burzhunova

Keyword(s):

Cervical Spine ◽

Clinical Practice ◽

Research Methods ◽

Neurological Disorders ◽

Cervical Vertebrae ◽

Clinical Manifestations ◽

Neurological Complications ◽

Timely Diagnosis ◽

Number Of Patients ◽

Genetically Determined

In clinical practice, a sufficiently large number of patients complain of neurological disorders caused by osteochondrosis of the cervical spine. Despite this, in some cases, the development and progression of this symptomatology may be due to an anomaly in the structure of the cervical spine (Klippel-Feil syndrome), which is genetically determined. Timely diagnosis of this pathology with the implementation of complex research methods allows you to develop individual tactics for each individual patient, taking into account the severity of clinical manifestations to slow the progression of complications.

Download Full-text

Neurological Complications of Middle East Respiratory Syndrome Coronavirus: A Report of Two Cases and Review of the Literature

Case Reports in Neurological Medicine ◽

10.1155/2016/3502683 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 33

Author(s):

Hussein Algahtani ◽

Ahmad Subahi ◽

Bader Shirah

Keyword(s):

Middle East ◽

Neurological Complications ◽

Critical Illness Polyneuropathy ◽

Asymptomatic Infection ◽

Middle East Respiratory Syndrome ◽

Systemic Complications ◽

Gastrointestinal Complications ◽

Icu Stay ◽

Pathological Mechanism ◽

Respiratory Tract Illness

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first discovered in September 2012 in Saudi Arabia. Since then, it caused more than 1600 laboratory-confirmed cases and more than 580 deaths among them. The clinical course of the disease ranges from asymptomatic infection to severe lower respiratory tract illness with multiorgan involvement and death. The disease can cause pulmonary, renal, hematological, and gastrointestinal complications. In this paper, we report neurological complications of MERS-CoV in two adult patients, and we hypothesize the pathophysiology. The first patient had an intracerebral hemorrhage as a result of thrombocytopenia, disseminated intravascular coagulation, and platelet dysfunction. The second case was a case of critical illness polyneuropathy complicating a long ICU stay. In these cases, the neurological complications were secondary to systemic complications and long ICU stay. Autopsy studies are needed to further understand the pathological mechanism.

Download Full-text

Neurological manifestations associated with SARS-CoV-2 infection: a narrative review

10.5327/1516-3180.442 ◽

2021 ◽

Author(s):

Poliana Rafaela dos Santos Araújo ◽

Kauan Alves Sousa Madruga ◽

Bruna Alves Rocha ◽

Lucas Oliveira Braga

Keyword(s):

Nervous System ◽

Meta Analysis ◽

Neurological Complications ◽

Neurological Symptoms ◽

Narrative Review ◽

Common Symptom ◽

Neurological Manifestations ◽

Cns Involvement ◽

Pubmed Database ◽

Critical Patients

Background: Coronavirus disease (COVID-19), once identified, soon spread globally, becoming a pandemic. Although patients present mainly with respiratory complaints, several neurological symptoms have been reported. Symptoms range from headache and nonspecific dizziness to seizures and cerebrovascular disease (CVD). It has also been shown that the severity of the infection is directly proportional to the development of neurological symptoms, especially CVD and changes in mental status. Objective: The present study aims to briefly review the neurological manifestations of COVID-19 and discuss the pathogenic mechanisms of Central Nervous System (CNS) involvement. Methods: This is an exploratory narrative review with a descriptive approach, consisting of an active search for scientific articles in the PubMed database. The descriptors “coronavirus infections”, “COVID-19” and “Nervous system” were used, with the Boolean operators “OR” and “AND”. Eighteen articles of systematic review and meta-analysis were included. Results: CNS manifestations included, among others: encephalitis, encephalopathy, consciousness decrease, headache, dizziness, acute myelitis, and stroke. As for the peripheral nervous system, skeletal muscle damage, chemosensory dysfunction, and Guillain-Barré syndrome were observed, with hyposmia being the most common symptom. CNS involvement may be related to a worse prognosis. Conclusion: The clinical involvement of the nervous system in COVID-19 is not uncommon, and can result in several neurological complications, especially in the most critical patients. The pathophysiological mechanisms of these events still need further investigation. In the meantime, physicians should value extra-respiratory symptoms ranging from hyposmia, to potentially fatal manifestations, such as stroke and encephalopathy.

Download Full-text

The Myocardial and Neuronal Infectivity of SARS-CoV-2 and Detrimental Outcomes

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2021-0390 ◽

2021 ◽

Author(s):

Ernest Herbert ◽

Dominique Fournier ◽

Waleed A. Al-Shaqha ◽

Mohamed Chahine

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Severe Acute Respiratory Syndrome ◽

Hospital Mortality ◽

Early Stage ◽

Neurological Complications ◽

Insufficient Data ◽

Neurological Manifestations ◽

Characteristic Features ◽

Neuronal Functions

The epidemiological outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alias COVID-19, began in Wuhan, Hubei, China, in late December and eventually turned into a pandemic that has led to 3.71+ million deaths and 173+ million infected cases worldwide. In addition to respiratory manifestations, COVID-19 patients with neurological and myocardial dysfunctions exhibit a higher risk of in-hospital mortality. The immune function tends to be affected by cardiovascular risk factors and is thus indirectly related to the prognosis of COVID-19 patients. Many neurological symptoms and manifestations have been reported in COVID-19 patients. However, detailed descriptions of the prevalence and characteristic features of these symptoms are restricted due to insufficient data. It is thus advisable for clinicians to be vigilant for both cardiovascular and neurological manifestations in order to detect them at an early stage to avoid inappropriate management of COVID-19 and to address the manifestations adequately. Patients with severe COVID-19 are notably more susceptible to developing cardiovascular and neurological complications than non-severe COVID-19 patients. This review focuses on the consequential outcomes of COVID-19 on cardiovascular and neuronal functions, including other influencing factors.

Download Full-text