Neurological Manifestations Of Coronavirus Disease 2019 Research Articles

A Systematic Review Unraveling the Intricate Neurological Spectrum of COVID-19: Manifestations, Complications, and Transformative Insights for Patient Care.

The coronavirus disease 2019 (COVID-19) pandemic has strained global healthcare and financial infrastructures. Neurological manifestations of COVID-19 have gained recognition, emphasizing the need for comprehensive research in this area. This systematic review aims to comprehensively examine the neurological manifestations and complications associated with COVID-19 and assess their prevalence, impact on patient outcomes, and potential relationships with comorbidities, while emphasizing the significance of ongoing research in this field. We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines. A comprehensive search of PubMed, Google Scholar, Science Direct, and ResearchGate databases was conducted to identify eligible studies focusing on COVID-19 patients, reporting neurological symptoms or complications, and published between 2020 and 2022 in English. The data extracted is performed in a Microsoft Excel spreadsheet. Two independent reviewers assessed study quality and bias using the AMSTAR 2 scale before inclusion. This systematic includes 12 systematic reviews and meta-analysis with 191,412 participants and average age of 60 years. Neurological symptoms included headaches, dizziness, anosmia, and ageusia. Complications ranged from cerebrovascular events to Guillain-Barré syndrome. Comorbidities, such as hypertension and diabetes, exacerbated severity. Mortality rates associated with neurological manifestations varied from 29.1% to 84.8%. The study underscores the complex neurological impact of COVID-19, affecting patients across age groups. Ongoing research is vital to understand mechanisms and develop targeted interventions, improving patient care and addressing pandemic consequences. This review provides a holistic view of COVID-19's neurological effects, emphasizing the need for sustained research efforts and collaborative endeavors to combat the neurological issues.

Brain Renin-Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS-CoV-2.

Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous system (CNS). The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS-CoV-2 infection and neurological manifestations. This study aimed to present an updated review of the role of brain RAS components, especially ACE2, in neurological complications induced by SARS-CoV-2 infection. Several routes of SARS-CoV-2 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID-19 patients, the olfactory nerve route was suggested as an early pathway for SARS-CoV-2 entry into the brain. In addition, a hematogenous route via disintegrations in the blood-brain barrier following an increase in systemic cytokine and chemokine levels and retrograde axonal transport, especially via the vagus nerve innervating lungs, have been described. Common nonspecific neurological symptoms in COVID-19 patients are myalgia, headache, anosmia, and dysgeusia. However, more severe outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, and stroke. Alterations in brain RAS components such as angiotensin II (Ang II) and ACE2 mediate neurological manifestations of SARS-CoV-2 infection, at least in part. Downregulation of ACE2 due to SARS-CoV-2 infection, followed by an increase in Ang II levels, leads to hyperinflammation and oxidative stress, which in turn accelerates neurodegeneration in the brain. Furthermore, ACE2 downregulation in the hypothalamus induces stress and anxiety responses by increasing corticotropin-releasing hormone. SARS-CoV-2 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID-19. It can be concluded that the neurological manifestations of COVID-19 may be partially associated with changes in brain RAS components.

HEADACHE MANIFESTATION OF COVID-19: A CASE SERIES AND NARRATIVE REVIEW

Despite the typical primary symptoms reported, the coronavirus disease 2019 (COVID-19) outbreak could be manifested as many symptoms. Neurological manifestations of COVID-19 are hypothesized to be caused by multiple pathophysiologies. As one of the possible prodromal symptoms in the absence of fever and respiratory symptoms, many individuals might be unaware of contracting COVID-19 infection and could possibly infect other people. This case series involved a hundred and twenty COVID-19 patients in which nine of them reported headaches as the chief complaint to provide the prevalence rate. Medical histories were assessed to provide the prevalence rate and laboratory findings of involved subjects. Narrative review of possible mechanisms of the manifestation were also denoted. To date, the proportion of non-specific manifestations as the first symptom needs to be further explored as it could be one of the initial symptoms and early manifestations of COVID-19.

Neurological Complications of SARS-CoV-2 Infection and COVID-19 Vaccines: From Molecular Mechanisms to Clinical Manifestations.

Coronavirus Disease 2019 (COVID-19) is an infectious disease, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), that reached pandemic proportions in 2020. Despite the fact that it was initially characterized by pneumonia and acute respiratory distress syndrome, it is now clear that the nervous system is also compromised in one third of these patients. Indeed, a significant proportion of COVID-19 patients suffer nervous system damage via a plethora of mechanisms including hypoxia, coagulopathy, immune response to the virus, and the direct effect of SARS-CoV-2 on endothelial cells, neurons, astrocytes, pericytes and microglia. Additionally, a low number of previously healthy individuals develop a variety of neurological complications after receiving COVID-19 vaccines and a large proportion of COVID-19 survivors experience longlasting neuropsychiatric symptoms. In conclusion, COVID-19 is also a neurological disease, and the direct and indirect effects of the virus on the nervous system have a significant impact on the morbidity and mortality of these patients. Here we will use the concept of the neurovascular unit, assembled by endothelial cells, basement membrane, perivascular astrocytes, neurons and microglia, to review the effects of SARS-CoV-2 in the nervous system. We will then use this information to review data published to this date on the neurological manifestations of COVID-19, the post- COVID syndrome and COVID-19 vaccines.

Acute Transverse Myelitis in a Paediatric Patient with Coronavirus Disease-19; a Case Report

: The number of reports of the extrapulmonary manifestations of the coronavirus disease 2019 (COVID-19) is increasing in the literature. The neurological manifestations of COVID-19 in pediatric patients, however, are not well studied. Acute transverse myelitis is among the neurological manifestations usually reported with viral infections. However, the development of transverse myelitis in pediatric patients following COVID-19 is extremely rare. We report a case of acute transverse myelitis in a previously healthy 11 years old female patient with COVID-19 who was asymptomatic before the onset of weakness.

Neurological Manifestations of COVID-19

Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV), which was first identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China [1]. It was initially reported to the WHO on December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a global health emergency [2, 3]. On March 11, 2020, the WHO declared COVID-19 a global pandemic, its first such designation since declaring H1N1 influenza a pandemic in 2009 [4]. Keywords: COVID-19, Neurological manifestations

Therapeutic Approaches to the Neurologic Manifestations of COVID-19.

As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain–Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01267-y.

Neurological manifestations of post-COVID-19 syndrome S1-guideline of the German society of neurology

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to COVID-19 (COrona VIrus Disease-2019). SARS-CoV-2 acute infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. Neurological manifestations are commonly reported during the post-acute phase and are also present in Long-COVID (LCS) and post-COVID-19 syndrome (PCS). In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of COVID-19. In December 2021 this S1 guideline was revised and guidance for the care of patients with post-COVID-19 syndrome regarding neurological manifestations was added. This is an abbreviated version of the post-COVID-19 syndrome chapter of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).

Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC

BackgroundNeurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients.MethodsIn the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome.ResultsOf the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5–14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9–8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients.ConclusionsBased on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Vitamin D and its Possible Relationship to Neuroprotection in COVID-19: Evidence in the Literature.

Vitamin D is a hormone involved in the regulation of important biological processes such as signal transduction, immune response, metabolic regulation and also in the nervous and vascular systems. To date, coronavirus disease 2019 (COVID-19) infection does not have a specific treatment. However, various drugs have been proposed, including those that attenuate the intense inflammatory response, and recently, the use of vitamin D, in clinical trials, as part of the treatment of COVID-19 has provided promising results. It has been observed in some clinical studies that the use of cholecalciferol (vitamin D3) and its two metabolites the circulating form, calcidiol or calcifediol (25-hydroxycalciferol, 25-(OH)-D), and the active form, calcitriol (1,25-(OH)2-D), in different doses, improve the clinical manifestations, prognosis, and survival of patients infected with COVID-19 probably because of its anti-inflammatory, antiviral and lung-protective action. In relation to the central nervous system (CNS) it has been shown, in clinical studies, that vitamin D is beneficial in some neurological and psychiatric conditions because of its anti-inflammatory and antioxidant properties, modulation of neurotransmitters actions, and regulation of calcium homeostasis between other mechanisms. It has been shown that COVID-19 infection induces CNS complications such as headache, anosmia, ageusia, neuropathy, encephalitis, stroke, thrombosis, cerebral hemorrhages, cytotoxic lesions, and psychiatric conditions and it has been proposed that the use of dietary supplements, as vitamin and minerals, can be adjuvants in this disease. In this review, the evidence of the possible role of vitamin D, and its metabolites, as a protector against the neurological manifestations of COVID-19 was summarized.

Encephalitis Associated With COVID-19 in A 7-year-old Boy: A Case Report

Coronaviruses (CoVs) are single-stranded RNA viruses described for &gt;50 years. Novel coronavirus (SARS-Coronavirus-2: SARS-CoV-2) emerged in Wuhan and has spread globally. Coronavirus Disease 2019 (COVID-19) symptoms are primarily pulmonary (fever, dry cough, fatigue, pneumonia); however, other organs can be affected, including the gastrointestinal tract, kidneys, liver, heart, and brain.&#x0D; Pediatric COVID-19 is milder than the adult’s type. Children with severe disease often have an underlying co-morbidity, such as chronic lung disease or immunosuppression.&#x0D; SARS-CoV-1, MERS-CoV, HCoV-OC43, and HCoV-229E are associated with neurological complications. Neurological manifestations of COVID-19 are not well understood in adults or children, and these manifestations are not rare. The number of patients with neurological manifestations has been increasing Recently, especially in the third peak of the disease.&#x0D; Early diagnosis and timely management may lead to a better outcome. There are limited reports of neurological complications in the pediatric population. Further studies are required for early diagnosis and better results. We reported the third case of encephalitis in children without any respiratory or gastrointestinal manifestation.&#x0D; A 7-year-old male was admitted with fever and loss of consciousness. He presented no respiratory or gastrointestinal symptoms. He reported no medical history and history of substance abuse. Laboratory findings confirm that neurological manifestations might be expected in covid-19 infections, despite the absence of respiratory symptoms. The patient was treated, and the level of consciousness was gradually improving. Supportive treatment and outpatient follow-up were recommended.

The characteristics of headache in COVID-19: A literature review

Coronavirus disease 2019 (COVID-19) has become outbreak in the world since December 2020. The higher incidence and transmission of COVID-19, the higher virulence of the disease. Besides respiratory manifestations, the most common symptoms in COVID-19 are neurological manifestations. The major neurological manifestations in COVID-19 are headache and dizziness. Headache is more common as chief complaint in emergency room and hospitalized patients than dizziness. Therefore, this review aims to outline the characteristics of headache in COVID-19. The conclusion of this review is that the characteristics of headache in COVID-19 are moderate-severe intensity, frontal-temporal region, pulsatile and tightening quality, constant duration and commonly associate with one or more COVID-19 symptoms.

Neuroimaging findings in hospitalized patients with COVID-19

BackgroundVariable neuroimaging findings have been reported in patients with coronavirus disease 2019 (COVID-19). In addition to respiratory symptoms, many neurologic manifestations of COVID-19 are increasingly reported and variable neuroimaging findings have been observed in patients with COVID-19. Our aim was to describe findings observed in hospitalized patients with COVID-19, presenting with acute neurologic manifestations and undergoing computed tomography (CT) or magnetic resonance imaging (MRI) of the brain.MethodsWe performed a retrospective study involving patients with laboratory-confirmed SARS-COV-2 infection, admitted to our hospital between July 1 and December 30, 2020. Patients who presented with acute neurologic symptoms and required neuroimaging were only included in the study. Neuroimaging examinations were evaluated for the presence of, infarction, hemorrhage and encephalopathy. The frequency of these findings was correlated with clinical variables, including presence of comorbidities, requirement for intensive care unit admission, and duration between admission and onset of neurologic signs and symptoms as documented in the hospital medical records.ResultsA total of 135 patients underwent at least one cross-sectional imaging of the brain, the median age of these patients was 63 years, and 72% were men. Disturbed level of consciousness was the most common neurologic symptom (80.7%). Acute neuroimaging findings were found in 34 patients (25.2%) including; acute ischemic infarcts (16/135; 11.9%), intracranial hemorrhages (9/135, 6.7%), cerebral venous thrombosis (2/135; 1.5%), posterior reversible encephalopathy syndrome (1/135; 0.7%), and hypoxic-ischemic encephalopathy (6/135, 4.4%). There was no statistically significant difference in patient age (p = 0.062), sex (0.257), presence of comorbidities (p = 0.204), intensive care unit admission (p = 0.326) and duration between admission and onset of neurologic signs and symptoms (p = 0.755), in patients with positive versus negative neuroimaging studies.ConclusionsOur study showed that cerebrovascular complications, ischemic and hemorrhagic were the most frequent imaging finding in hospitalized patients with COVID-19. Knowledge about these potentially serious complications can help optimize management for these patients.

Neurological Manifestations in COVID-19 in Three Waves of the Pandemic: An Inpatient Study from India.

Though severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) virus primarily affects respiratory system, neurological involvement is well known. To describe the neurological manifestations of coronavirus disease 2019 (COVID-19) during three waves of the pandemic. This was an ambispective observational single-centre study to describe the neurological manifestations of COVID-19 infection among inpatients from a tertiary care referral centre in Western India from March 2020 to January 2022. Out of 14,822 patients admitted with COVID-19, 307 (2.07%) had neurological manifestations. Neurological manifestations were seen in 1.87% in first wave (onset to 10 Feb 21); 2.37% in second wave (Feb 11, 2021 to Dec 31, 2021) and 6.26% in third wave (Jan 1, 2022 to Jan 31, 2022). The most common neurological manifestations were encephalopathy (34.5%), ischemic stroke (32.1%), and acute symptomatic seizures (8.8%). Encephalopathy (p = 0.028) was more common in first wave while seizures were more common in third wave (p = 0.001). In patients with encephalopathy, hypoxia (p = 0.0001), shock (p = 0.001), renal involvement (p = 0.002), and sepsis (p = 0.033) were associated with higher mortality; while those with no systemic involvement had better survival (p = 0.0001). Among patients with ischemic stroke, 32.1% did not have any traditional vascular risk factors. These patients were 9 years younger and required 6 days less hospitalization than patients of stroke with vascular risk factors. SARS-CoV-2 produces many central and peripheral nervous system manifestations. Encephalopathy was more common in first wave while acute symptomatic seizures were more common in third wave. Encephalopathy was most common neurological manifestation with progressively higher mortality with increased number of systemic comorbidities. Ischemic stroke was seen in patients who had vascular risk factors as well as in patients without them.

ACUTE MULTIPLE TERRITORIES STROKE IN AN ANTICOAGULATED COVID-19 PATIENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: The complications of coronavirus disease 2019 (COVID-19) involve the nervous system, including acute stroke, which is currently linked to the hypercoagulable state associated with COVID-19 [1]. CASE PRESENTATION: Our patient is a 70-year-old man with past medical history of hypertension and diabetes mellitus who presented to the emergency department with shortness of breath and fatigue for five days duration. Vitaly was stable, except for saturating 88% on the room air. He was alert and oriented on physical exam, lung exam was remarkable for bibasilar rales. He had no focal neurological deficits. Lab Work showed elevated COVID-19 markers. Chest x-ray showed left-sided infiltrates. He was admitted to the respiratory care unit and was started on dexamethasone, remdesevir, ceftriaxone, azithromycin, and enoxaparin prophylactic dose. His oxygen requirement continued to increase, and on the ninth day, he was placed on a nasal high-flow oxygen device with 60 liters FiO2 of 90%. On the eleventh day, the patient developed right facial droop, aphasia and right-sided weakness. The National Institutes of Health Stroke Scale was 16. Code stroke was called, and a brain computed tomography scan without contrast revealed cortical infarct in the high left parietal cerebral hemisphere without hemorrhage. Computed tomography angiography (CTA) of the head and neck showed mild narrowing within the middle cerebral artery. Magnetic resonance imaging, later on, showed left medial frontoparietal infarct in ACA territory. Cardiology workup confirmed no cardiac pathology. The neurology team decided not to start the tissue plasminogen activator (tPA) because he was out of the tPA window, and as no large vessel occlusion was found, a thrombectomy was not performed. DISCUSSION: COVID-19 infection is considered a highly coagulable status, especially the severe form of the disease. The pathophysiology behind this is not well understood yet. However, Severe COVID-19 is associated with cytokine activation, which activates endothelial cells and mononuclear cells with expression of tissue factor leading to coagulation cascade activation [2]. It has also been observed that COVID-19 can induce Antiphospholipid antibodies, which might play a role in thrombosis in those patients [3]. Our case confirms that COVID-19 induced acute stroke can occur in multiple territories despite the patient being well anticoagulated. CONCLUSIONS: Acute stroke should be suspected in COVID-19 patients with acute neurological changes even if the patient is on prophylactic anticoagulation. Frequent screening neurological examination can lead to early detection and treatment of acute stroke. REFERENCE #1: Verstrepen, K., Baisier, L. & De Cauwer, H. Neurological manifestations of COVID-19, SARS and MERS. Acta Neurol Belg 120, 1051–1060 (2020). https://doi.org/10.1007/s13760-020-01412-4 REFERENCE #2: Beyrouti R, Adams ME, Benjamin L, et alCharacteristics of ischaemic stroke associated with COVID-19Journal of Neurology, Neurosurgery & Psychiatry 2020;91:889-891. REFERENCE #3: Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C, Zhao J, Sun X, Tian R, Wu W, Wu D, Ma J, Chen Y, Zhang D, Xie J, Yan X, Zhou X, Liu Z, Wang J, Du B, Qin Y, Gao P, Qin X, Xu Y, Zhang W, Li T, Zhang F, Zhao Y, Li Y, Zhang S. Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med. 2020 Apr 23;382(17):e38. doi: 10.1056/NEJMc2007575. Epub 2020 Apr 8. PMID: 32268022;PMCID: PMC7161262. DISCLOSURES: No relevant relationships by Abdul Rahman Al Armashi, source=Web Response No relevant relationships by Ameed Bawwab, source=Web Response No relevant relationships by Arthur Boyd, source=Web Response No relevant relationships by Kanchi Patell, source=Web Response No relevant relationships by Keyvan Ravakhah, source=Web Response No relevant relationships by Francisco Somoza-Cano, source=Web Response

Neurological Manifestations of COVID-19

The year 2020 started with the news of a novel coronavirus, severe acute respiratory syndrome corona virus 2(SARS-CoV2), induced disease in China which was termed as coronavirus disease 2019 (COVID-19). This viralinfection soon became pandemic and affected millions of people all over the world. The virus preferentiallyaffects respiratory system causing dry cough and fever, but has the tendency to spread to different organs in the body leading to multiple organ failure. Recent evidences show that corona virus can invade nervous system and damage it. This review is based on different articles and case reports that provide an evidence of neuro-virulent nature of COVID-19 and its consequences. The neuro-invasive property of the virus is divided into threecategories i) Central Nervous System (CNS) manifestations, ii) Peripheral Nervous System (PNS) manifestationsand iii) Skeletal Muscle damage. Headache and dizziness were observed to be common symptoms for CNS,whereas loss of smell and taste for PNS damage due to COVID-19. The aim of this review is, to develop anunderstanding of the devastating effects of COVID-19 on nervous system for the early recognition of virusinduced damage. This information can be used for the development of better therapeutic strategies.

Neurological manifestations of COVID-19: a clinical approach

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 which attacks the respiratory tract and has been declared a global pandemic by the World Health Organization. The disease has a very wide clinical spectrum which can be manifested as asymptomatic to critical conditions. SARS-CoV-2 shows a neurotropism proven by its identification in the cerebrospinal fluid and brain vascular endothelial. The complete mechanism of how the virus invades the human nervous system is yet to be identified. Thus, every neurologist needs to follow the progressivity of COVID-19 symptoms involving the nervous system.

Neurological manifestations in COVID-19: an overview

The novel coronavirus disease 2019 (COVID-19) is a causative agent of severe lower respiratory tract infection in patients. Since its discovery in December 2019, COVID-19 has spread to five continents and to this date, affected approximately 6,260,000 people. COVID-19 patients typically present with symptoms related to the respiratory system while neurological manifestations have scarcely been reported. Neurological presentations of COVID-19 infection are classified into two groups: CNS symptoms and peripheral nervous system (PNS) symptoms. CNS symptoms include headache, dizziness, loss of consciousness, convulsion, ataxia and acute cerebrovascular disease. The PNS symptoms consist of hypoplasia, hyposmia, hypogeusia and neuralgia. The association between COVID-19 and neurological problems needs further clarification and warrants detailed microbiological and pathological studies to better understand the virus and its impact on the brain and nervous system.

Neurological manifestations of COVID-19: with emphasis on Iranian patients

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has instigated a global pandemic as a formidable and highly contagious infectious disease. Although the respiratory system remains the most frequently affected organ, several case reports have revealed that the complications are not merely limited to the respiratory system, and neurotropic and neuroinvasive properties have also been observed, leading to neurological diseases. In the present paper, it was intended to review the possible neuroinvasive routes of SARS-CoV-2 and its mechanisms that may cause neurological damage. Additionally, the neurological manifestations of COVID-19 across the globe were discussed with emphasis on Iran, while highlighting the impact of SARS-CoV-2 on the central and peripheral nervous systems.

Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity.

Background and purposeNeurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID‐19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID‐19.MethodsNineteen patients with neurological symptoms and mild to critical COVID‐19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity.ResultsNeurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms.ConclusionsAlthough limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID‐19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.