Neurological Complications Of COVID-19 Research Articles

Post COVID Guillain Barre Syndrome (GBS) in paediatric COVID unit of Dhaka Medical College: A case series

SARS Cov-2 infection presents with mild respiratory illness but has evidence of multisystem involvement in little percentage, though the severity of infection is variable in children. Neurological manifestations may vary from headache, dizziness, olfactory or taste dysfunction to specific syndromes including meningoencephalitis, stroke, and acute transverse myelitis and Guillain- Barre syndrome (GBS). But there is little evidence worldwide about neurological complications of COVID-19 in children. Here we reporting five cases of post COVID-19 GBS with relevant literature review. J Dhaka Med Coll. 2022; 31(2) : 232-236

Post COVID Guillain Barre Syndrome (GBS) in paediatric COVID unit of Dhaka Medical College: A case series

SARS Cov-2 infection presents with mild respiratory illness but has evidence of multisystem involvement in little percentage, though the severity of infection is variable in children. Neurological manifestations may vary from headache, dizziness, olfactory or taste dysfunction to specific syndromes including meningoencephalitis, stroke, and acute transverse myelitis and Guillain- Barre syndrome (GBS). But there is little evidence worldwide about neurological complications of COVID-19 in children. Here we reporting five cases of post COVID-19 GBS with relevant literature review. J Dhaka Med Coll. 2022; 31(2) : 232-236

COVID-19-associated encephalopathy: connection between neuroinflammation and microbiota-gut-brain axis.

While neurological complications of COVID-19, such as encephalopathy, are relatively rare, their potential significant impact on long-term morbidity is substantial, especially given the large number of infected patients. Two proposed hypotheses for the pathogenesis of this condition are hypoxia and the uncontrolled release of proinflammatory cytokines. The gut microbiota plays an important role in regulating immune homeostasis and overall gut health, including its effects on brain health through various pathways collectively termed the gut-brain axis. Recent studies have shown that COVID-19 patients exhibit gut dysbiosis, but how this dysbiosis can affect inflammation in the central nervous system (CNS) remains unclear. In this context, we discuss how dysbiosis could contribute to neuroinflammation and provide recent data on the features of neuroinflammation in COVID-19 patients.

Abstract WP324: MCA/FeCl 3 Thromboembolic Model, an Easily Reproducible Model for COVID-19-Induced Embolic Cerebrovascular Complications

COVID-19 neurological complications such as strokes and cognitive impairment have been reported. Yet the molecular mechanisms are under investigation. A mild and reproducible thromboembolic model will be a helpful tool for investigating COVID-thromboembolic complications. The aim of this study is to investigate the middle cerebral artery/ferric chloride (MCA/FeCl 3 ) thromboembolic model as an easily and reproducible model for COVID-19-induced cerebrovascular embolic complications. Methods: SARS-CoV-2 spike-protein of the alpha variant were injected intravenously (4 ug/animal) in K18 (transgenic knock-in humanized ACE2 in epithelial cells). Seven days later, MCA/FeCl 3 thromboembolic model was induced in K18 mice by exposing the MCA and placing filter paper wet with FeCl 3 . Laser speckle imaging was used for the assessment of blood flow and recanalization after 1,2,6, and 24 hrs. TTC was used to assess the infarct volume. Cognitive function was assessed using a novel object recognition test. Cerebral vascular density and blood-brain barrier (BBB) were assessed by immunohistochemistry staining using Iso-B4 lectin and Occludin-5 antibody. Results: SARS-CoV-2 spike-protein caused a significant increase in the time required for vascular recanalization as detected by laser speckle imaging compared to control K18 mice. (P<0.05). In parallel, spike protein caused a significant increase in infarct size compared to control K18 mice (P<0.05). Our immunohistochemistry showed that spike protein decreased vascular density and increased vascular rarefaction compared to control K18 mice (P<0.05). A novel object recognition test showed that spike protein increased cognitive dysfunction compared to control (P<0.05). Western blot analysis showed that spike protein increased inflammatory markers and decreased BBB tight junction protein compared to control K18 mice (P<0.05). In conclusion , the MCA/FeCl 3 thromboembolic model is an easily reproducible mouse model to examine COVID-19-induced stroke and cerebrovascular complications.

Investigating Spine and Spinal Cord Complications of COVID-19

Background and Aim: SARS-COV-2 can present with pulmonary, renal, gastrointestinal, hematological, and neurological manifestations. Neurological manifestations may occur after or before COVID-19 symptoms and signs. Spine and spinal cord complications are documented as neurological complications of COVID-19. Spinal cord pathology following COVID-19 showed inflammatory myelopathy and suspected cord ischemia. The most frequent presentation of COVID-19 myelitis is non-enhancing central expansile cord T2 signal changes, but it can present with lateral and dorsal column-specific disease and in some cases with negative magnetic resonance imaging (MRI). There is no known documented mechanism for spinal cord involvement in COVID-19 infection, but it seems as a post-infectious immunological and post-inflammatory disorder and reaction. Viral infection of SARS-CoV-2 can cause demyelination of the brain and spinal cord and also can exacerbate the known primary demyelinating disorders. Methods and Materials/Patients: This is a narrative study about the spinal cord complications of COVID-19. To provide up-to-date information, we precisely reviewed COVID-19 articles on spine and spinal cord complications. Based on the keywords COVID-19, SARS-CoV-2, spine, and spinal cord, all the related articles were taken from Google Scholar, PubMed, and Medline and were precisely studied. Results: There are reported cases of COVID-19 spine and spinal cord involvement. There is no documented mechanism for these involvements but the possible mechanisms are direct invasion, cytokine storm, coagulopathy, and an autoimmune response. The routine therapy of such complications is the treatment of these complications with other primary causes with a poor and unsatisfactory response of myelopathy to treatment; however, early diagnosis and vigilance of such involvement improve outcome. Conclusion: COVID-19 can cause spine and spinal cord complications in some patients without a known incidence rate of such complications. The pathogenesis is not completely known; therefore, more conclusive studies are obligatory to improve our information on COVID-19 spinal cord and spine complications.

Role of Imaging in Diagnosis of Neurological Complications of COVID-19

Background The COVID-19 pandemic has become a challenging world issue after its emergence in December 2019. Despite its most characteristic symptom of respiratory distress, patients with COVID-19 have also shown neurologic manifestations. Aim of the Work To investigate the yield of neuroimaging in patients with COVID-19 undergoing CT or MR imaging of the brain and to describe associated imaging findings. Patients and Methods A descriptive cross–sectional study conducted at Ain Shams University Hospitals over a course of eight months from December 2020 to July 2021. All patients with confirmed COVID-19 infection who presented with neurological symptoms and underwent neuroimaging were included. Results 39 patients were included in the study, with both adults (84.6%) and children (15.4%). Acute ischemic stroke is found to be the most common complication among adult group (48.5%) followed by Post-covid invasive fungal sinusitis (45.5%). Among the children, the neurological complications are rare but severe including vasculitis (50%), infarctions (33.3 %), cerebritis (16.7 %), venous sinus thrombosis (16.7 %), PRES (16.7 %) and non-specific white matter signal abnormality (16.7 %). Conclusion COVID-19 primarily affects the respiratory system. However, neurological involvement is not uncommon and can result in serious complications if not detected and managed early. These complications in some cases can even precede the respiratory symptoms or may be the only symptoms in COVID-19 patients. Therefore, a high index of suspicion is required while dealing with such cases for proper treatment and prevention.

Visual and neurological complications of COVID-19

Visual and neurological complications of COVID-19

Cardiovascular and Neurological Complications of COVID-19: A Narrative Review.

A novel coronavirus emerged in China in late 2019 as a disease named coronavirus disease 2019. This pathogen was initially identified as causing a respiratory syndrome, but later, it was found that COVID-19 could also affect other body systems, such as the neurological and cardiovascular systems. For didactic purposes, cardiovascular and neurological manifestations of SARS-CoV-2 have been classified in three different groups: acute complications, late complications, and post-vaccine complications. Therefore, the following study has the goal to summarize and disseminate the present knowledge about the cardiovascular and neurological manifestations of COVID-19 based on the latest and most up-to-date data available and, thus, promote more prepared medical care for these conditions as the medical team is updated. Based on what is brought on this revision and its understanding, the medical service becomes more aware of the causal relationship between some conditions and COVID-19 and can better prepare for the most prevalent conditions to associate and, consequently, to treat patients earlier. Therefore, there is a chance of better prognoses in this context and the need to increase the number of studies about complications related to SARS-CoV-2 infection for a better understanding of other associated conditions.

European Working Group on SARS-CoV-2: Current Understanding, Unknowns, and Recommendations on the Neurological Complications of COVID-19.

Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlighting the current knowns and unknowns of the post-COVID-19 condition. In this review, we draw upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, as well as explore the current published literature, to evaluate a range of topics associated with the neurological complications of the post-COVID-19 condition. As a result, we have provided a comprehensive review of the topic. The European Working Group on SARS-CoV-2 Many essential questions surrounding COVID-19 remain unanswered, including its neurological complications and associated sequalae. In this review, we aim at identifying the current gaps in our understanding of post-COVID-19 neurological sequalae and suggest how future studies should be undertaken to fill these gaps. This review will draw upon the current biological and mechanistic understanding of COVID-19 and post-COVID-19 complications to discuss the clinically relevant aspects associated with the neurological manifestations of post-COVID-19 syndrome. From our discussions, the following questions were considered highly relevant for contemplation.

An eye to the future: Acute and long-term neuro-ophthalmological and neurological complications of COVID-19.

COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration.

Short, medium and long term neurological manifestations and outcome in Covid-19 Patients

Background and objectives: 
 There is a need to improve the understanding of Covid-19 neurological complications in a temporal manner. The objective of our study was to find out temporal relationship of neurological manifestations and outcome in Covid-19 Patients.
 Methods:
 This was a multi-center observational study from six centers in Pakistan. Data of covid patients with six months follow up was retrospectively collected from the hospital records. Time periods were divided into short-term (< 1 month), medium-term (2-3 months) and long-term (>4 months). SPSS version 26.0 (SPSS Inc., Chicago, IL, USA) was used to analyze the data.
 Results:
 Neurological manifestations were reported in 208 out of 905 covid patients. One-hundred-twenty-five (60%) developed neurological manifestations within one month, 62 (30%) developed within 2-3 months and 21 (10%) developed between 4-6 months. Most common manifestations within one month included cerebrovascular disease (59%), neuromuscular disorders (14%) and neuropsychiatric disorders (10%). Common manifestations in 2-3 months group included neuromuscular manifestations (32%), neuropsychiatric manifestations (19%), cerebrovascular diseases (14 %), myalgia or musculoskeletal pain (14%), and vertigo, hearing problems or tinnitus (14%). Common manifestations in 4-6 months group included neuromuscular disorders (33%) cerebrovascular diseases (19%), fatigue / malaise (9%) anosmia/dysgeusia (9%) and Bell’s palsy (25%). The long-term patients differed from the short-term patients by a mean younger age on presentation (44.7 vs. 59 years), female predominance (52% vs. 28%), higher asymptomatic Covid infection (29% vs. 14%), better clinical outcomes (mean mRS of 1.6 vs. 3), and low mortality (0 vs 18%).
 Conclusion:
 Neurological manifestations of covid infection may differ based on time duration since infection. Vascular complications are high in early period while neuromuscular manifestations are high in late period.

Host Genetic Variants Linked to COVID-19 Neurological Complications and Susceptibility in Young Adults-A Preliminary Analysis.

To date, multiple efforts have been made to use genome-wide association studies (GWAS) to untangle the genetic basis for SARS-CoV-2 infection susceptibility and severe COVID-19. However, data on the genetic-related effects of SARS-CoV-2 infection on the presence of accompanying and long-term post-COVID-19 neurological symptoms in younger individuals remain absent. We aimed to examine the possible association between SNPs found in a GWAS of COVID-19 outcomes and three phenotypes: SARS-CoV-2 infection, neurological complications during disease progression, and long-term neurological complications in young adults with a mild-to-moderate disease course. University students (N = 336, age 18-25 years, European ancestry) with or without COVID-19 and neurological symptoms in anamnesis comprised the study sample. Logistic regression was performed with COVID-19-related phenotypes as outcomes, and the top 25 SNPs from GWAS meta-analyses and an MR study linking COVID-19 and cognitive deficits were found. We replicated previously reported associations of the FURIN and SLC6A20 gene variants (OR = 2.36, 95% CI 1.31-4.24) and OR = 1.94, 95% CI 1.08-3.49, respectively) and remaining neurological complications (OR = 2.12, 95% CI 1.10-4.35 for SLC6A20), while NR1H2 (OR = 2.99, 95% CI 1.39-6.69) and TMPRSS2 (OR = 2.03, 95% CI 1.19-3.50) SNPs were associated with neurological symptoms accompanying COVID-19. Our findings indicate that genetic variants related to a severe COVID-19 course in adults may contribute to the occurrence of neurological repercussions in individuals at a young age.

Neurological complications of COVID-19 and SARS-CoV-2 vaccination: an update

The respiratory infectious disease COVID-19, which emerged in 2019, has affected the world population over a brief period. In 2020, the disease was declared a pandemic by the World Health Organization. Although most COVID-19 patients primarily develop respiratory symptoms, neurological symptoms have been observed. Neurological symptoms are usually mild and non-specific. However, some patients could experience life-threatening neurological symptoms. With the increase in the incidence of COVID-19, the disease spectrum of patients with central and peripheral nervous system involvement has expanded significantly compared to the previous period. Lack of awareness has caused delays in diagnosis and treatment; therefore, updating the disease spectrum of neurological complications of COVID-19 is necessary. After COVID-19 claimed millions of lives, researchers found that some vaccines may induce autoimmune inflammatory responses in the nervous system via molecular mimicry, leading to SARS-CoV-2 vaccine-related neurological deficits. These neurological complications are often ignored by clinicians, delaying diagnosis and treatment; it is essential to study cases of vaccine-associated neurological complications. Therefore, we summarize the neurological complications of COVID-19 and nervous system adverse reactions caused by SARS-CoV-2 vaccines to help clinicians and public health service personnel understand these rare complications. Avoiding delays in diagnosis and treatment would ensure the safety of COVID-19 patients and SARS-CoV-2 vaccine recipients.

Medical University Of Sofia

Ultimately, contemporary Information and Communication Technologies (ICT) were introduced in the rehabilitation practice. We use Exoskeletons, virtual reality, robotic rehabilitation with Locomat (Hocoma system for balance and gait training) and ThyroMotion system (for grasp training). Our purpose was to emphasize the impact of robotic rehabilitation in the process of recovery of patients with neurological complications of COVID-19, as follows: cerebral vascular accidents, spinal ischemic stroke, relapses of multiple sclerosis, Guillain-Barre syndrome, development of rare diseases (as cerebellar ataxia or amyotrophic lateral sclerosis /motor neuron disease), etc. We present typical and rare clinical cases (consequences and complications of COVID-19), treated by robotic neurorehabilitation. Our results demonstrated positive effects of ICT-application on the neuroplasticity, functional recovery and quality of life of neurological patients. We consider introduction of robotics as necessary tool in the process of neurorehabilitation.

Neurological Complications and Consequences of the Novel Coronavirus COVID-19 Infection in Elderly and Senile Patients (Literature Review)

Based on available publications, the article systematizes information about some forms of lesions of the central nervous system (CNS), their pathogenesis and clinical manifestations in the case of COVID-19. The risk factors, mechanisms of development, diagnostic approach, and the age characteristics of patients with neurological complications of COVID-19 are discussed. The specific mechanisms of the neuroinvasiveness and neurovirulence of the SARS-CoV-2 virus, regardless of the age of patients and the presence of risk factors, lead to systemic damage to the endothelium of small-caliber vessels, generalized thrombovasculitis, and an increased risk of ischemic and hemorrhagic strokes. At the same time, the most vulnerable category is elderly and senile patients with cardiovascular and metabolic disorders (arterial hypertension, obesity, diabetes mellitus), which sharply worsen treatment outcomes. The clinical experience accumulated during the COVID-19 pandemic indicates the development of the following most frequent post-covid neurological complications and consequences in mainly elderly and senile patients: cranial mononeuropathies, chemosensory dysfunction, encephalopathy, insomnia, stroke, acute meningoencephalitis, acute disseminated encephalomyelitis, acute polyneuropathy Guillain–Barré syndrome, and transverse myelitis. The benefits of vaccination against COVID-19 far outweigh the risks of possible post-vaccination neurological complications and consequences, especially in elderly and senile patients.

Neurological complications of COVID-19 in children and its effect on the quality of life

Coronavirus disease 2019, a pandemic that recently enveloped the world is a highly transmissible respiratory disease leading to 2,409,011 deaths in 2021. The most prevalent clinical symptoms in coronavirus disease 2019 patients are fever, cough, shortness of breath, and other respiratory issues. Coronavirus disease 2019 exhibits various neurological manifestations and complications which are quite rare in children. The purpose of this research is to review the available information about neurological complications of Coronavirus disease 2019 in children. Coronavirus disease 2019 is linked to neurological complications in children, including headaches, encephalopathy, and certain other neurological disorders. Involvement of the nervous system in coronavirus infection is either immediate, during the progression of the disease, after recovery, or as part of multisystem inflammatory syndrome in children. The clinical manifestations of coronavirus disease in new-borns and infants with neurological complications vary and can affect the whole neuraxis, affecting the central nervous system, peripheral nervous system, or both. In addition, children with multisystem inflammatory syndrome and coronavirus had severe neurological complications such as encephalitis, epilepsy, coma, dementia, dysgeusia or ageusia, aseptic meningitis, stroke, dysarthria, dysphagia, cerebellar ataxia, axial hypotonia, and drowsiness. Seizures in children are normally reported when they are suffering from fever due to viral infection. Neurological complications in children are rare and limited literature is available in this regard. More comprehensive, clinical follow-up studies can significantly contribute to understanding the relationship among coronavirus disease effects and neurological complications among children.

Preventing COVID-19 neurological complications.

Preventing COVID-19 neurological complications.

Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

Retroelements play a key role in brain functioning in humans and other animals, since they represent dynamic regulatory elements controlling the expression of specific neuron types. The activity of retroelements in the brain is impaired under the influence of SARS-CoV-2, penetrating the blood-brain barrier. We propose a new concept, according to which the neurological complications of COVID-19 and their long-term effects are caused by modified expression of retroelements in neurons due to viral effect. This effect is implemented in several ways: a direct effect of the virus on the promoter regions of retroelement-encoding genes, virus interaction with miRNAs causing silencing of transposons, and an effect of the viral RNA on the products of retroelement transcription. Aging-related physiological activation of retroelements in the elderly is responsible for more severe course of COVID-19. The associations of multiple sclerosis, Parkinson’s disease, Guillain-Barré syndrome, acute disseminated encephalomyelitis with coronavirus lesions also indicate the role of retroelements in such complications, because retroelements are involved in the mechanisms of the development of these diseases. According to meta-analyses, COVID-19-caused neurological complications ranged 36.4-73%. The neuropsychiatric consequences of COVID-19 are observed in patients over a long period after recovery, and their prevalence may exceed those during the acute phase of the disease. Even 12 months after recovery, unmotivated fatigue, headache, mental disorders, and neurocognitive impairment were observed in 82%, 60%, 26.2-45%, and 16.2-46.8% of patients, correspondingly. These manifestations are explained by the role of retroelements in the integration of SARS-CoV-2 into the human genome using their reverse transcriptase and endonuclease, which results in a long-term viral persistence. The research on the role of specific retroelements in these changes can become the basis for developing targeted therapy for neurological consequences of COVID-19 using miRNAs, since epigenetic changes in the functioning of the genome in neurons, affected by transposons, are reversible.

(Epi)transcriptomics in cardiovascular and neurological complications of COVID-19.

Although systemic inflammation and pulmonary complications increase the mortality rate in COVID-19, a broad spectrum of cardiovascular and neurological complications can also contribute to significant morbidity and mortality.The molecular mechanisms underlying cardiovascular and neurological complications during and after SARS-CoV-2 infection are incompletely understood. Recently reported perturbations of the epitranscriptome of COVID-19 patients indicate that mechanisms including those derived from RNA modifications and non-coding RNAs may play a contributing role in the pathogenesis of COVID-19.In this review paper, we gathered recently published studies investigating (epi)transcriptomic fluctuations upon SARS-CoV-2 infection, focusing on the brain-heart axis since neurological and cardiovascular events and their sequelae are of utmost prevalence and importance in this disease.

Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery.

Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide–drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.