Investigating Neurological Manifestations of SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Mozafar M
PROVIDER: S-EPMC8384098 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Investigating Neurological Manifestations of SARS-CoV-2.
Mozafar Maryam M Mirmotalebisohi Seyed Amir SA Sameni Marzieh M Zali Hakimeh H
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 20210824 4
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Project description:During the first wave of infections, neurological symptoms in Coronavirus Disease 2019 (COVID-19) patients raised particular concern, suggesting that, in a subset of patients, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could invade and damage cells of the central nervous system (CNS). Indeed, up to date several in vitro and in vivo studies have shown the ability of SARS-CoV-2 to reach the CNS. Both viral and/or host related features could explain why this occurs only in certain individuals and not in all the infected population. The aim of the present study was to evaluate if onset of neurological manifestations in COVID-19 patients was related to specific viral genomic signatures. To this end, viral genome was extracted directly from nasopharyngeal swabs of selected SARS-CoV-2 positive patients presenting a spectrum of neurological symptoms related to COVID-19, ranging from anosmia/ageusia to more severe symptoms. By adopting a whole genome sequences approach, here we describe a panel of known as well as unknown mutations detected in the analyzed SARS-CoV-2 genomes. While some of the found mutations were already associated with an improved viral fitness, no common signatures were detected when comparing viral sequences belonging to specific groups of patients. In conclusion, our data support the notion that COVID-19 neurological manifestations are mainly linked to patient-specific features more than to virus genomic peculiarities.
| S-EPMC9246207 | biostudies-literature
Project description:ObjectiveTo perform an updated review of the literature on the neurological manifestations of COVID-19-infected patients METHODS: A PRISMA-guideline-based systematic review was conducted on PubMed, EMBASE, and SCOPUS. Series reporting neurological manifestations of COVID-19 patients were studied.Results39 studies and 68,361 laboratory-confirmed COVID-19 patients were included. Up to 21.3% of COVID-19 patients presented neurological symptoms. Headache (5.4%), skeletal muscle injury (5.1%), psychiatric disorders (4.6%), impaired consciousness (2.8%), gustatory/olfactory dysfunction (2.3%), acute cerebrovascular events (1.4%), and dizziness (1.3%), were the most frequently reported neurological manifestations. Ischemic stroke occurred among 1.3% of COVID-19 patients. Other less common neurological manifestations were cranial nerve impairment (0.6%), nerve root and plexus disorders (0.4%), epilepsy (0.7%), and hemorrhagic stroke (0.15%). Impaired consciousness and acute cerebrovascular events were reported in 14% and 4% of patients with a severe disease, respectively, and they were significantly higher compared to non-severe patients (p < 0.05). Individual patient data from 129 COVID-19 patients with acute ischemic stroke (AIS) were extracted: mean age was 64.4 (SD ± 6.2), 78.5% had anterior circulation occlusions, the mean NIHSS was 15 (SD ± 7), and the intra-hospital mortality rate was 22.8%. Admission to the intensive care unit (ICU) was required among 63% of patients.ConclusionThis updated review of literature, shows that headache, skeletal muscle injury, psychiatric disorders, impaired consciousness, and gustatory/olfactory dysfunction were the most common neurological symptoms of COVID-19 patients. Impaired consciousness and acute cerebrovascular events were significantly higher among patients with a severe infection. AIS patients required ICU admission in 63% of cases, while intra-hospital mortality rate was close to 23%.
| S-EPMC7597753 | biostudies-literature
Project description:In December 2019, an outbreak of illness caused by a novel coronavirus (2019-nCoV, subsequently renamed SARS-CoV-2) was reported in Wuhan, China. Coronavirus disease 2019 (COVID-19) quickly spread worldwide to become a pandemic. Typical manifestations of COVID-19 include fever, dry cough, fatigue, and respiratory distress. In addition, both the central and peripheral nervous system can be affected by SARS-CoV-2 infection. These neurological changes may be caused by viral neurotropism, by a hyperinflammatory and hypercoagulative state, or even by mechanical ventilation-associated impairment. Hypoxia, endothelial cell damage, and the different impacts of different ventilatory strategies may all lead to increased stress and strain, potentially exacerbating the inflammatory response and leading to a complex interaction between the lungs and the brain. To date, no studies have taken into consideration the possible secondary effect of mechanical ventilation on brain recovery and outcomes. The aim of our review is to provide an updated overview of the potential pathogenic mechanisms of neurological manifestations in COVID-19, discuss the physiological issues related to brain-lung interactions, and propose strategies for optimization of respiratory support in critically ill patients with SARS-CoV-2 pneumonia.
| S-EPMC7434832 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a global concern involves infections in multiple organs. Much of the research up to now has been descriptive on neurological manifestations followed by SARS-CoV-2 infection. Despite considerable efforts on effective SARS-CoV-2 vaccine, novel therapeutic options for COVID-19 comorbidities are warranted. One of the fast ways to introduce possible effective drugs for clinical trials is bioinformatics methods. We have conducted a comprehensive enrichment analysis of genes involved in SARS-CoV-2 and neurological disorders associated with COVID-19. For this purpose, gene sets were extracted from the GeneWeaver database. To find out some significant enriched findings for common genes between SARS-CoV-2 and its neurological disorders, several practical databases were used. Finally, to repurpose an efficient drug, DrugBank databases were used. Overall, we detected 139 common genes concerning SARS-CoV-2 and their neurological disorders. Interestingly, our study predicted around 6 existing drugs (ie, carvedilol, andrographolide, 2-methoxyestradiol, etanercept, polaprezinc, and arsenic trioxide) that can be used for repurposing. We found that polaprezinc (zinc l-carnosine) drug is not investigated in the context of COVID-19 till now and it could be used for the treatment of COVID-19 and its neurological manifestations. To summarize, enrichment and network data get us a coherent picture to predict drug repurposing to speed up clinical trials.
| S-EPMC8216348 | biostudies-literature
Project description:Background There are no published cases of tonic-clonic seizures and posterior bilateral blindness during pregnancy and Severe Acute Respiratory Syndrome (SARS) Coronavirus (COV) 2 (SARS-COV-2) infection. We do not just face new and unknown manifestations, but also how different patient groups are affected by SARS-COV-2 infection, such as pregnant women. Coronavirus Disease 2019 (COVID-19), preeclampsia, eclampsia and posterior reversible leukoencephalopathy share endothelium damage and similar pathophysiology. Case presentation A 35-year-old pregnant woman was admitted for tonic-clonic seizures and SARS-COV-2 infection. She had a normal pregnancy control and no other symptoms before tonic-clonic seizures development. After a Caesarean section (C-section) she developed high blood pressure, and we initiated antihypertensive treatment with labetalol, amlodipine and captopril. Few hours later she developed symptoms of cortical blindness that resolved in 72?h with normal brain computed tomography (CT) angiography. Conclusion The authors conclude that SARS COV-2 infection could promote brain endothelial damage and facilitate neurological complications during pregnancy.
| S-EPMC7538036 | biostudies-literature
Project description:BackgroundNeurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population.MethodsA literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged < 18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches.ResultsA total of 843 nonduplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6,985 individuals were included, where 12.8% of hospitalized patients experienced neurocognitive impairments: MIS-C (24.2%), neuroinflammation (10.1%), and encephalopathy (8.1%) were the most common disorders; headaches (16.8%) and seizures (3.8%) were the most common symptoms. Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%).ConclusionOur findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.
| S-EPMC10029078 | biostudies-literature
Project description:BackgroundAccumulating studies demonstrated that patients with coronavirus disease 2019(COVID-19) could develop a variety of neurological manifestations and long-term neurological sequelae, which may be different from the strains. At the peak of the Omicron variant outbreak in Shanghai, China, no relevant epidemiological data about neurological manifestations associated with this strain was reported.ObjectiveTo investigate neurological manifestations and related clinical features in patients with mild to moderate COVID-19 patients with Omicron variant.MethodsA self-designed clinical information registration form was used to gather the neurological manifestations of mild to moderate COVID-19 patients admitted to a designated hospital in Shanghai from April 18, 2022 to June 1, 2022. Demographics, clinical presentations, laboratory findings, treatments and clinical outcomes were compared between patients with and without neurological manifestations.ResultsOne hundred sixty-nine(48.1 %) of 351 patients diagnosed with mild to moderate COVID-19 exhibited neurological manifestations, the most common of which were fatigue/weakness(25.1 %) and myalgia(20.7 %), whereas acute cerebrovascular disease(0.9 %), impaired consciousness(0.6 %) and seizure(0.6 %) were rare. Younger age(p = 0.001), female gender(p = 0.026) and without anticoagulant medication(p = 0.042) were associated with increasing proportions of neurological manifestations as revealed by multivariate logistic regressions. Patients with neurological manifestations had lower creatine kinase and myoglobin levels, as well as higher proportion of patchy shadowing on chest scan. Vaccination status, clinical classification of COVID-19 and clinical outcomes were similar between the two groups.ConclusionsNearly half of the involved patients have neurological manifestations which were relatively subjective and closely associated with younger age, female gender and without anticoagulation. Patients with neurologic manifestations may be accompanied by increased lung patchy shadowing.
| S-EPMC9726211 | biostudies-literature
Project description:BackgroundThe spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents.MethodsWe did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group. Paediatric neurologists were invited to notify any children and adolescents (age <18 years) admitted to hospital with neurological or psychiatric disorders in whom they considered SARS-CoV-2 infection to be relevant to the presentation. Patients were excluded if they did not have a neurological consultation or neurological investigations or both, or did not meet the definition for confirmed SARS-CoV-2 infection (a positive PCR of respiratory or spinal fluid samples, serology for anti-SARS-CoV-2 IgG, or both), or the Royal College of Paediatrics and Child Health criteria for paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Individuals were classified as having either a primary neurological disorder associated with COVID-19 (COVID-19 neurology group) or PIMS-TS with neurological features (PIMS-TS neurology group). The denominator of all hospitalised children and adolescents with COVID-19 was collated from National Health Service England data.FindingsBetween April 2, 2020, and Feb 1, 2021, 52 cases were identified; in England, there were 51 cases among 1334 children and adolescents hospitalised with COVID-19, giving an estimated prevalence of 3·8 (95% CI 2·9-5·0) cases per 100 paediatric patients. 22 (42%) patients were female and 30 (58%) were male; the median age was 9 years (range 1-17). 36 (69%) patients were Black or Asian, 16 (31%) were White. 27 (52%) of 52 patients were classified into the COVID-19 neurology group and 25 (48%) were classified into the PIMS-TS neurology group. In the COVID-19 neurology group, diagnoses included status epilepticus (n=7), encephalitis (n=5), Guillain-Barré syndrome (n=5), acute demyelinating syndrome (n=3), chorea (n=2), psychosis (n=2), isolated encephalopathy (n=2), and transient ischaemic attack (n=1). The PIMS-TS neurology group more often had multiple features, which included encephalopathy (n=22 [88%]), peripheral nervous system involvement (n=10 [40%]), behavioural change (n=9 [36%]), and hallucinations at presentation (n=6 [24%]). Recognised neuroimmune disorders were more common in the COVID-19 neurology group than in the PIMS-TS neurology group (13 [48%] of 27 patients vs 1 [<1%] of 25 patients, p=0·0003). Compared with the COVID-19 neurology group, more patients in the PIMS-TS neurology group were admitted to intensive care (20 [80%] of 25 patients vs six [22%] of 27 patients, p=0·0001) and received immunomodulatory treatment (22 [88%] patients vs 12 [44%] patients, p=0·045). 17 (33%) patients (10 [37%] in the COVID-19 neurology group and 7 [28%] in the PIMS-TS neurology group) were discharged with disability; one (2%) died (who had stroke, in the PIMS-TS neurology group).InterpretationThis study identified key differences between those with a primary neurological disorder versus those with PIMS-TS. Compared with patients with a primary neurological disorder, more patients with PIMS-TS needed intensive care, but outcomes were similar overall. Further studies should investigate underlying mechanisms for neurological involvement in COVID-19 and the longer-term outcomes.FundingUK Research and Innovation, Medical Research Council, Wellcome Trust, National Institute for Health Research.
| S-EPMC8279959 | biostudies-literature
Project description:The recent outbreak of coronavirus disease 2019 (COVID-19) has gained considerable attention worldwide due to its increased potential to spread and infect the general population. COVID-19 primarily targets the human respiratory epithelium but also has neuro-invasive potential. Indeed, neuropsychiatric manifestations, such as fatigue, febrile seizures, psychiatric symptoms, and delirium, are consistently observed in COVID-19. The neurobiological basis of neuropsychiatric COVID-19 symptoms is not fully understood. However, previous evidence about systemic viral infections pointed to an ongoing neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells from the periphery. Microglia cells mediate the overproduction of inflammatory cytokines, free radicals, and damage signals, culminating with neurotoxic consequences. Semi-synthetic second-generation tetracyclines, including minocycline (MINO) and doxycycline (DOXY), are safe bacteriostatic agents that have remarkable neuroprotective and anti-inflammatory properties. Promising results have been obtained in clinical trials using tetracyclines for major psychiatric disorders, such as schizophrenia and major depression. Tetracyclines can inhibit microglial reactivity and neuroinflammation by inhibiting nuclear factor kappa B (NF-kB) signaling, cyclooxygenase 2, and matrix metalloproteinases (MMPs). This drug class also has a broad profile of activity against bacteria associated with community-based pneumonia, including atypical agents. COVID-19 patients are susceptible to secondary bacterial infections, especially those on invasive ventilation. Therefore, we suggest tetracyclines' repurposing as a potential treatment for COVID-19 neuropsychiatric manifestations. These drugs can represent a valuable multi-modal treatment for COVID-19-associated neuroinflammatory alterations based on their broad antimicrobial profile and neuroinflammation control.
| S-EPMC7854870 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, clinical research on its neurological manifestations is thus far limited. In this study, we aimed to systematically collect and investigate the clinical manifestations and evidence of neurological involvement in COVID-19.MethodsThree medical (Medline, Embase, and Scopus) and two preprints (BioRxiv and MedRxiv) databases were systematically searched for all published articles on neurological involvement in COVID-19 since the outbreak. All included studies were systematically reviewed, and selected clinical data were collected for meta-analysis via random-effects.ResultsA total of 41 articles were eligible and included in this review, showing a wide spectrum of neurological manifestations in COVID-19. The meta-analysis for unspecific neurological symptoms revealed that the most common manifestations were fatigue (33.2% [23.1-43.3]), anorexia (30.0% [23.2-36.9]), dyspnea/shortness of breath (26.9% [19.2-34.6]), and malaise (26.7% [13.3-40.1]). The common specific neurological symptoms included olfactory (35.7-85.6%) and gustatory (33.3-88.8%) disorders, especially in mild cases. Guillain-Barré syndrome and acute inflammation of the brain, spinal cord, and meninges were repeatedly reported after COVID-19. Laboratory, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19.ConclusionsNeurological manifestations are various and prevalent in COVID-19. Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses. More studies should be conducted to explore the role of neurological manifestations in COVID-19 progression and to verify their underlying mechanisms.
| S-EPMC7288253 | biostudies-literature