Neurological Symptoms Of COVID-19 Research Articles

Promising Strategies to Reduce the SARS-CoV-2 Amyloid Deposition in the Brain and Prevent COVID-19-Exacerbated Dementia and Alzheimer's Disease.

The COVID-19 pandemic, caused by infection with the SARS-CoV-2 virus, is associated with cognitive impairment and Alzheimer's disease (AD) progression. Once it enters the brain, the SARS-CoV-2 virus stimulates accumulation of amyloids in the brain that are highly toxic to neural cells. These amyloids may trigger neurological symptoms in COVID-19. The meningeal lymphatic vessels (MLVs) play an important role in removal of toxins and mediate viral drainage from the brain. MLVs are considered a promising target to prevent COVID-19-exacerbated dementia. However, there are limited methods for augmentation of MLV function. This review highlights new discoveries in the field of COVID-19-mediated amyloid accumulation in the brain associated with the neurological symptoms and the development of promising strategies to stimulate clearance of amyloids from the brain through lymphatic and other pathways. These strategies are based on innovative methods of treating brain dysfunction induced by COVID-19 infection, including the use of photobiomodulation, plasmalogens, and medicinal herbs, which offer hope for addressing the challenges posed by the SARS-CoV-2 virus.

Cell invasive amyloid assemblies from SARS-CoV-2 peptides can form multiple polymorphs with varying neurotoxicity.

The neurological symptoms of COVID-19, often referred to as neuro-COVID include neurological pain, memory loss, cognitive and sensory disruption. These neurological symptoms can persist for months and are known as Post-Acute Sequalae of COVID-19 (PASC). The molecular origins of neuro-COVID, and how it contributes to PASC are unknown, however a growing body of research highlights that the self-assembly of protein fragments from SARS-CoV-2 into amyloid nanofibrils may play a causative role. Previously, we identified two fragments from the SARS-CoV-2 proteins, Open Reading Frame (ORF) 6 and ORF10, that self-assemble into neurotoxic amyloid assemblies. Here we further our understanding of the self-assembly mechanisms and nano-architectures formed by these fragments and their biological responses. By solubilising the peptides in a fluorinated solvent, we eliminate insoluble aggregates in the starting materials (seeds) that change the polymorphic landscape of the assemblies. The resultant assemblies are dominated by structures with higher free energies (e.g. ribbons and amorphous aggregates) that are less toxic to cultured neurons but do affect their mitochondrial respiration. We also show the first direct evidence of cellular uptake of viral amyloids. This work highlights the importance of understanding the polymorphic behaviour of amyloids and the correlation to neurotoxicity, particularly in the context of neuro-COVID and PASC.

Self-Reported Neurological Symptoms Two Years After Hospital Discharge Among COVID-19 Survivors.

The acute stage of COVID-19 often presents with neurological manifestations. This study aims to investigate the long-term neurological effects on survivors. This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19. Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms. Neurological symptoms are common among COVID-19 survivors, especially in severe cases.

Morphologic Findings in the Cerebral Cortex in COVID-19: Association of Microglial Changes with Clinical and Demographic Variables.

Despite the enormous interest in COVID-19, there is no clear understanding of the mechanisms underlying the neurological symptoms in COVID-19. Microglia have been hypothesized to be a potential mediator of the neurological manifestations associated with COVID-19. In most existing studies to date, morphological changes in internal organs, including the brain, are considered in isolation from clinical data and defined as a consequence of COVID-19. We performed histological immunohistochemical (IHC) studies of brain autopsy materials of 18 patients who had died from COVID-19. We evaluated the relationship of microglial changes with the clinical and demographic characteristics of the patients. The results revealed neuronal alterations and circulatory disturbances. We found an inverse correlation between the integral density Iba-1 (microglia/macrophage-specific marker) IHC staining and the duration of the disease (R = -0.81, p = 0.001), which may indicate a reduced activity of microglia and do not exclude their damage in the long-term course of COVID-19. The integral density of Iba-1 IHC staining was not associated with other clinical and demographic factors. We observed a significantly higher number of microglial cells in close contact with neurons in female patients, which confirms gender differences in the course of the disease, indicating the need to study the disease from the standpoint of personalized medicine.

Elevated Expression of RGS2 May Underlie Reduced Olfaction in COVID-19 Patients.

Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator of odorant receptors, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC = 14.5, Padj = 1.69 × 10−5 and FC = 2.4; Padj = 0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathway(s) may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.

Multisystem Inflammatory Syndrome in Children and Long COVID: The SARS-CoV-2 Viral Superantigen Hypothesis.

Multisystem inflammatory syndrome in children (MIS-C) is a febrile pediatric inflammatory disease that may develop weeks after initial SARS-CoV-2 infection or exposure. MIS-C involves systemic hyperinflammation and multiorgan involvement, including severe cardiovascular, gastrointestinal (GI) and neurological symptoms. Some clinical attributes of MIS-C—such as persistent fever, rashes, conjunctivitis and oral mucosa changes (red fissured lips and strawberry tongue)—overlap with features of Kawasaki disease (KD). In addition, MIS-C shares striking clinical similarities with toxic shock syndrome (TSS), which is triggered by bacterial superantigens (SAgs). The remarkable similarities between MIS-C and TSS prompted a search for SAg-like structures in the SARS-CoV-2 virus and the discovery of a unique SAg-like motif highly similar to a Staphylococcal enterotoxin B (SEB) fragment in the SARS-CoV-2 spike 1 (S1) glycoprotein. Computational studies suggest that the SAg-like motif has a high affinity for binding T-cell receptors (TCRs) and MHC Class II proteins. Immunosequencing of peripheral blood samples from MIS-C patients revealed a profound expansion of TCR β variable gene 11-2 (TRBV11-2), which correlates with MIS-C severity and serum cytokine levels, consistent with a SAg-triggered immune response. Computational sequence analysis of SARS-CoV-2 spike further identified conserved neurotoxin-like motifs which may alter neuronal cell function and contribute to neurological symptoms in COVID-19 and MIS-C patients. Additionally, autoantibodies are detected during MIS-C, which may indicate development of post-SARS-CoV-2 autoreactive and autoimmune responses. Finally, prolonged persistence of SARS-CoV-2 RNA in the gut, increased gut permeability and elevated levels of circulating S1 have been observed in children with MIS-C. Accordingly, we hypothesize that continuous and prolonged exposure to the viral SAg-like and neurotoxin-like motifs in SARS-CoV-2 spike may promote autoimmunity leading to the development of post-acute COVID-19 syndromes, including MIS-C and long COVID, as well as the neurological complications resulting from SARS-CoV-2 infection.

Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don’t understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.

COVID-ассоциированная нейроофтальмопатия. Проблемы диагностического поиска и лечения

Since the beginning of the COVID-19 pandemic, a large number of reports on extrapulmonary manifestations of the disease have appeared, sometimes focusing on complex cases and challenging diagnostic tasks. Neuroophthalmological manifestations of COVID-19 include opticoneuritis, acute transverse myelitis, viral encephalitis, toxic encephalopathy, leukoencephalopathy, acute disseminated encephalomyelitis and some other conditions. 30.8% of patients with neurological symptoms of COVID-19 have idiopathic intracranial hypertension. The breadth of the diagnostic search complicates the task of the doctor to choose right diagnostic measures and treatment tactics. This article presents the clinical observation of a patient with ophthalmopathy and idiopathic intracranial hypertension during the post-COVID period. The case deserves special attention in the context of differential diagnosis with autoimmune diseases. We also present current publications on the topic of ophthalmopathy of various etiologies, including a new coronavirus infection, focusing on its role in the development of ocular and neurological symptoms. The current epidemiological situation implies the mandatory consideration of infectious pathology during diagnostics search. Understanding the impact of COVID-19 on human organs and systems and timely diagnosis will help to reduce the time spent on ineffective treatment and expensive diagnostic measures.

Persons with Co-Existing Neurological Disorders: Risk Analysis, Considerations and Management in COVID-19 Pandemic.

Increasing reports of neurological symptoms in COVID-19 patient's warrant clinicians to adopt and define the standardized diagnostic and managing protocols in order to investigate the linkage of neurological symptoms in COVID-19. Encephalitis, anosmia, acute cerebrovascular disease and ageusia are some of the emerging neurological manifestations which are reported in several cohort studies on hospitalized patients with COVID-19. Although the COVID-19 pandemic is primarily associated with infection of the respiratory tract system, but measures like lockdown and restricted physical movements to control the spread of this infection will certainly have neurobehavioural implications. Additionally, some of the patients with pre-existing neurological manifestations like epilepsy, Parkinson's and Alzheimer's disease are more prone to infection and demand extra care as well as improvised treatment. In this review, we have focused on the neurovirological clinical manifestations associated with the COVID-19 pandemic. Although the prevalence of neurovirological manifestations is rare increasing reports cannot be ignored and needs to be discussed thoroughly with respect to risk analysis and considerations for developing a management strategy. This also helps in defining the burden of neurological disorders associated with COVID-19 patients.

Abstract 53: Covid-19 Spike-protein Causes Cerebrovascular Rarefaction And Deteriorates Cognitive Functions In A Mouse Model Of Humanized ACE2

COVID-19 pandemic has affected our health and economy. Clinical trials confirmed multiple neurological symptoms due to COVID-19, ranging from headaches, insomnia to stroke, and encephalopathy. More studies are required to unravel the cellular and molecular mechanisms to find a cure for these neurological symptoms. Here, we investigate the effect of COVID-19 spike protein (S-protein) on the cerebrovasculature and cognitive functions in two mouse models that express humanized ACE-2 (h ACE2), a receptor essential for cellular infection and COVID-19 internalization. We hypothesize that COVID-19 S-protein causes cognitive dysfunction via the deterioration of cerebrovascular functions. Methods: S-protein was either injected intravenously or directly into the hippocampus of K-18 (h ACE2 in epithelial cells) or global h-ACE2 knock-in (h ACE2 KI) mice or wild-type mice. Cognitive functions were assessed by Y-maze and Barnes maze. Cerebrovascular density was determined using confocal 3-D image reconstruction. Human brain microvascular endothelial cells (HBMVEC) were treated with S-protein and assessed for apoptosis and inflammatory markers using immunoblotting and RT-PCR. K-18 and h-ACE2 KI mice received intraocular injections of S-protein; retinas were evaluated for vascular cell death and inflammation. Results: S-protein injections caused significant deterioration in memory and learning function of K-18 and h-ACE2 KI mice but not in the wild-type mice (P<0.05). S-protein significantly increased inflammatory mediators, cytokine production, and apoptosis in the brains and HBMVECs (P<0.05). Significant cerebrovascular rarefaction was detected only in K-18 and h-ACE2 KI mice compared to wild-type mice (P<0.05). Retinal vascular cell death and inflammation were significantly increased after S-protein injection. (P<0.05) Conclusions: COVID-19 spike protein decreases cognitive function via increased endothelial cell inflammation, apoptosis, and cerebrovascular rarefaction. Humanized ACE2 animal models are excellent and reliable for investigating the neurological symptoms of COVID-19.

Headache, anosmia, ageusia and other neurological symptoms in COVID-19: a cross-sectional study

BackgroundNeurological symptoms are frequent among patients with COVID-19. Little is known regarding the repercussions of neurological symptoms for patients and how these symptoms are related to one another.ObjectivesTo determine whether there is an association between the neurological symptoms in patients with COVID-19, and to characterize the headache.MethodThis was a cross-sectional study. All hospital inpatients and health workers at the Hospital Universitario Oswaldo Cruz with a PCR-confirmed COVID-19 infection between March and June 2020 were considered for the study and were interviewed by telephone at least 2-months after the acute phase of the disease. These patients were identified by the hospital epidemiological surveillance department. A semi-structured questionnaire was used containing sociodemographic and clinical data and the ID-Migraine.ResultsA total of 288 patients was interviewed; 53.1% were male; with a median age of 49.9 (41.5–60.5) years; 91.7% presented some neurological symptom; 22.2% reported some neurological symptom as the symptom that troubled them most during COVID-19. Neurological symptoms were: ageusia (69.8%), headache (69.1%), anosmia (67%), myalgia (44.4%), drowsiness (37.2%), agitation (20.8%); mental confusion (14.9%), syncope (4.9%) and epileptic seizures (2.8%). Females, those who presented with fever, sore throat, anosmia/ageusia and myalgia also presented significantly more with headache (logistic regression). The most frequent headache phenotype was a non-migraine phenotype, was of severe intensity and differed from previous headaches. This persisted for more than 30 days in 18% and for more than 90 days in 10% of patients. Thirteen percent of those with anosmia and 11% with ageusia continued with these complaints after more than 90 days of the acute phase of the disease. Aged over 50 years, agitation and epileptic seizures were significantly associated with mental confusion (logistic regression).ConclusionHeadache is frequent in COVID-19, is associated with other symptoms such as fever, sore throat, anosmia, ageusia, and myalgia, and may persist beyond the acute phase of the disease.

Evaluation of the Quality and Reliability of Youtube Videos on Neurological Symptoms of COVID-19

Purpose The objective of this study was to investigate scientific and quality accuracy of videos related to neurological symptoms of COVID -19 on YouTube. Methods YouTube searches was performed using keywords “COVID -19 Neurological Symptoms” and the first 50 YouTube videos about Neurological Symptoms of COVID -19 with the highest view counts were evaluated by one neurologist and one infectious disease specialist with DISCERN and JAWA scoring systems. Results Videos uploaded by health channels (50%), news channels (26%), physicians (22%), or patients (2%). The mean Video Power Index value was 95.51. The mean DISCERN and JAMA scores were 46.59±10.90, and 2.87±0.65. Health Channel mean DISCERN and JAMA scores were significantly higher than News Channel scores. There is no statistically significant correlation between DISCERN or JAMA scores and view counts, view rate, comment counts, like counts, or dislike counts. Conclusion Correct use of Youtube can play an important role in successfully conducting the COVID-19 outbreak. With the increase of the publication of these videos by Neurologists, the spread of false information can be minimized.

The incidence and pathophysiology of neurological symptoms in COVID-19

The central nervous system seems to be quite vulnerable to SARS-CoV-2, leading to a variety of alteration pathways, high incidence and variability of the neurological symptoms of COVID-19. The COVID-19 symptoms, possibly associated with alteration to the central nervous system, include hyperthermia, shortness of breath, fatigue, headache, dizziness, dysphonia, dysphagia, hyposmia and anosmia, hypogeusia and ageusia, impairment of consciousness. The impairment of olfaction and gustation are the most common symptoms of the nervous system alteration (98% and 70%, respectively), which is most likely a consequence of the alteration of the receptors. Presumably the pathogenesis of dysphonia and dysphagia may involve neurodegenerative mechanisms or may be associated with a predominantly demyelinating alteration of the caudal cranial nerves. Pathomorphological findings in the brain of the COVID-19 patients include diffuse hypoxic and focal ischemic injuries of various sizes up to ischemic infarctions (in thrombosis of large arteries); microangiopathy; vasculitis; diapedetic and confluent hemorrhages with possible progression to hemorrhagic infarctions and rarely intracerebral hematomas. Acute cerebrovascular accident worsens the course of COVID-19 and can worsen the clinical outcome, taking into account the mechanisms of the central nervous system alteration in highly contagious coronavirus infections (SARS-CoV, MERS, SARS-CoV-2), including embolism, hypoxia, neurodegeneration, systemic inflammatory response and immune-mediated alteartion to the nervous tissue. A fairly rare complication of coronavirus infection, however, acute myelitis requires attention due to the severity of neurological disorders. The literature data show high incidence and polymorphism of the symptoms of the central nervous system alteration, as well as the important role of the cerebrovascular and neurodegenerative pathogenesis of brain alteration in COVID-19, which is taken into account in examining and treating the patients with new coronavirus infection. (1 figure, bibliography: 61 refs)

PDZ-Containing Proteins Targeted by the ACE2 Receptor.

Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residue segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein-interacting domains called PSD-95/Dlg/ZO-1 (PDZ). Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high-throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants’ values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role in ACE2 internalization and recycling that could be of benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in the neurological symptoms of COVID-19.

Most prevalent symptoms associated with headache in COVID-19 patients in the acute phase: a systematic review

IntroductionConsidering the frequency of headache among the neurological symptoms of COVID-19, there is a need to understand other manifestations associated with this complaint.ObjectiveTo review the literature regarding the most prevalent symptoms associated with headache in patients diagnosed with COVID-19.MethodA systematic literature review was carried out on studies that evaluated published articles about clinical characteristics and headache associated symptoms in patients diagnosed with COVID-19.ResultsAmong the 1,190 patients in the analyzed studies, the following signs and symptoms were associated with headache: fever, hyposmia, anosmia, ageusia, phonophobia, dehydration, prostration and symptoms of the gastrointestinal tract.ConclusionHeadache was the main neurological symptom of COVID-19, among the main associated symptoms are fever, hyposmia or anosmia, ageusia and phonophobia.

Neurological manifestations in COVID-19 patients and their application in predicting fatal disease: A retrospective cohort study

BackgroundTo explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients.MethodsA retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records.ResultsOf 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9–18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78–11.73), male (OR = 1.73, 95% CI 1.22–2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23–2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0–10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11–20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87–55.16).ConclusionNeurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

Neurological Symptoms of COVID-19: The Zonulin Hypothesis.

The irruption of SARS-CoV-2 during 2020 has been of pandemic proportions due to its rapid spread and virulence. COVID-19 patients experience respiratory, digestive and neurological symptoms. Distinctive symptom as anosmia, suggests a potential neurotropism of this virus. Amongst the several pathways of entry to the nervous system, we propose an alternative pathway from the infection of the gut, involving Toll-like receptor 4 (TLR4), zonulin, protease-activated receptor 2 (PAR2) and zonulin brain receptor. Possible use of zonulin antagonists could be investigated to attenuate neurological manifestations caused by SARS-CoV-19 infection.

Neurological symptoms in COVID-19: a cross-sectional monocentric study of hospitalized patients

BackgroundThe SARS-Coronavirus-2 (SARS-CoV-2) invades the respiratory system, causing acute and sometimes severe pulmonary symptoms, but turned out to also act multisystematically with substantial impact on the brain. A growing number of studies suggests a diverse spectrum of neurological manifestations. To investigate the spectrum of symptoms, we here describe the neurological manifestations and complications of patients with proven SARS-CoV-2 infection who have been hospitalized at the RWTH University Hospital Aachen, Germany.MethodsBetween March and September 2020, we evaluated common symptoms, clinical characteristics, laboratory (including cerebrospinal fluid (CSF) analysis), radiological, and electroencephalography (EEG) data from 53 patients admitted with a positive SARS-CoV-2 polymerase chain reaction (PCR). We used the Montreal Cognitive Assessment Test (MoCA) to screen for cognitive impairment, when feasible. We compared critically ill and non-critically ill patients categorized according to the presence of Acute Respiratory Distress Syndrome (ARDS).ResultsMajor clinical neurological features of hospitalized COVID-19 patients were coordination deficits (74%), cognitive impairment (61.5%), paresis (47%), abnormal reflex status (45%), sensory abnormalities (45%), general muscle weakness and pain (32%), hyposmia (26%), and headache (21%). Patients with ARDS were more severely affected than non-ADRS patients. 29.6% of patients with ARDS presented with subarachnoid bleedings, and 11.1% showed ischemic stroke associated with SARS-CoV-2 infection. Cognitive deficits mainly affected executive functions, attention, language, and delayed memory recall. We obtained cerebrospinal fluid (CSF) by lumbar puncture in nine of the 53 patients, none of which had a positive SARS-CoV-2 PCR.ConclusionsIn line with previous findings, our results provide evidence for a range of SARS-CoV-2-associated neurological manifestations. 26% of patients reported hyposmia, emphasizing the neuro-invasive potential of SARS-CoV-2, which can enter the olfactory bulb. It can therefore be speculated that neurological manifestations may be caused by direct invasion of the virus in the CNS; however, PCR did not reveal positive intrathecal SARS-CoV-2. Therefore, we hypothesize it is more likely that the para-infectious severe pro-inflammatory impact of COVID-19 is responsible for the neurological deficits including cognitive impairment. Future studies with comprehensive longitudinal assessment of neurological deficits are required to determine potential long-term complications of COVID-19.

Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms.

SARS-CoV-2 infection can associate diverse neurological manifestations. Several studies have provided proof to support the theory of neurotropic involvement of SARS-CoV-2. Alpha-synuclein has been described as a native antiviral factor within neurons, and upregulation of this protein can be seen in animals that suffered other neuroinvasive infections. To assess if increased expression of this protein takes place in COVID-19 patients with neurological symptoms, we analyzed serum total alpha-synuclein levels in three groups: seven COVID-19 patients with myoclonus, Parkinsonism and/or encephalopathy; thirteen age- and sex-matched COVID-19 patients without neurological involvement and eight age- and sex-matched healthy controls. We did not find differences among them. In a subset of four patients, the change in serum alpha-synuclein before and after the onset of neurological symptoms was not significant either. Cerebrospinal fluid alpha-synuclein levels were also similar between neurological COVID-19 and healthy controls. Overall, these results cannot support the hypothesis of alpha-synuclein upregulation in humans with neurological symptoms in COVID-19. Further research taking into account a larger group of COVID-19 patients including the whole spectrum of neurological manifestations and disease severity is needed.

Neurological symptoms of COVID-19

Objective. Some viral infections can have a harmful effect on the functioning of the nervous system and can even cause serious neurological damage. This work aims to review the results of studies published so far concerning neurological complications in people infected with coronaviruses, especially SARS-CoV-2, and possible mechanisms responsible for nervous system damage. Literature review. Recently, there have been reports that coronaviruses, including SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), cause acute respiratory disease, exhibit neurotropic properties and can also cause neurological symptoms. There are studies published showing that these viruses may penetrate to the brain and cerebrospinal fluid. Conclusions. Coronaviruses are still poorly understood, so it seems important to study the potential impact of SARS-CoV-2 infections on the nervous system. It seems appropriate that patients infected with SARS-CoV-2 should be early evaluated for neurological symptoms, including headache and impaired consciousness.