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Potential neuroinvasive pathways of SARS-CoV-2: Deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19).

ABSTRACT: Coronavirus disease-2019 (COVID-19) was declared a global pandemic on 11 March 2020. Scientists and clinicians must acknowledge that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to attack the human body in multiple ways simultaneously and exploit any weaknesses of its host. A multipronged attack could potentially explain the severity and extensive variety of signs and symptoms observed in patients with COVID-19. Understanding the diverse tactics of this virus to infect the human body is both critical and incredibly complex. Although patients diagnosed with COVID-19 have primarily presented with pulmonary involvement, viral invasion, and injury to diverse end organs is also prevalent and well documented in these patients, but has been largely unheeded. Human organs known for angiotensin-converting enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra pulmonary tissues with confirmed invasion by SARS-CoV-2. Initial multiple organ involvement may present with vague signs and symptoms to alert health care professionals early in the course of COVID-19. Another example of an ongoing, yet neglected element of the syndromic features of COVID-19, are the reported findings of loss of smell, altered taste, ataxia, headache, dizziness, and loss of consciousness, which suggest a potential for neural involvement. In this review, we further deliberate on the neuroinvasive potential of SARS-CoV-2, the neurologic symptomology observed in COVID-19, the host-virus interaction, possible routes of SARS-CoV-2 to invade the central nervous system, other neurologic considerations for patients with COVID-19, and a collective call to action.

SUBMITTER: Baig AM

PROVIDER: S-EPMC7300748 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.

Project description:IntroductionGiven that the success of vaccines against coronavirus disease 2019 (COVID-19) relies on herd immunity, identifying patients at risk for vaccine hesitancy is imperative-particularly for those at high risk for severe COVID-19 (i.e., minorities and patients with neurological disorders).MethodsAmong patients from a large neuroscience institute in Hawaii, vaccine hesitancy was investigated in relation to over 30 sociodemographic variables and medical comorbidities, via a telephone quality improvement survey conducted between 23 January 2021 and 13 February 2021.ResultsVaccine willingness (n = 363) was 81.3%. Univariate analysis identified that the odds of vaccine acceptance reduced for patients who do not regard COVID-19 as a severe illness, are of younger age, have a lower Charlson Comorbidity Index, use illicit drugs, or carry Medicaid insurance. Multivariable logistic regression identified the best predictors of vaccine hesitancy to be: social media use to obtain COVID-19 information, concerns regarding vaccine safety, self-perception of a preexisting medical condition contraindicated with vaccination, not having received the annual influenza vaccine, having some high school education only, being a current smoker, and not having a prior cerebrovascular accident. Unique amongst males, a conservative political view strongly predicted vaccine hesitancy. Specifically for Asians, a higher body mass index, while for Native Hawaiians and other Pacific Islanders (NHPI), a positive depression screen, both reduced the odds of vaccine acceptance.ConclusionUpon identifying the variables associated with vaccine hesitancy amongst patients with neurological disorders, our clinic is now able to efficiently provide ancillary COVID-19 education to sub-populations at risk for vaccine hesitancy. While our results may be limited to the sub-population of patients with neurological disorders, the findings nonetheless provide valuable insight to understanding vaccine hesitancy.

Project description:BackgroundWest Nile Virus (WNV) is a mosquito-borne flavivirus that has caused ongoing seasonal epidemics in the United States since 1999. It is estimated that ≤1% of WNV-infected patients will develop neuroinvasive disease (West Nile encephalitis and/or myelitis) that can result in debilitating morbidities and long-term sequelae. It is essential to collect longitudinal information about the recovery process and to characterize predicative factors that may assist in therapeutic decision-making in the future.MethodsWe report a longitudinal study of the neurological outcomes (as measured by neurological examination, Glascow Coma Scale, and Modified Mini-Mental State Examination) for 55 subjects with WNV neuroinvasive disease (confirmed by positive CSF IgM) assessed on day 7, at discharge, and on days 14, 30, and 90. The neurological outcome measures were coma (presence and degree), global cognitive status, presence of cranial neuropathy, tremors and/or weakness.ResultsAt initial clinical presentation 93% presented with a significant neurological deficit (49% with weakness, 35% with tremor, and 16% with cranial neuropathy). The number of patients with a cognitive deficit fell from 25 at initial evaluation to 9 at their last evaluation. Cranial neuropathy was present in 9 at onset and in only 4 patients at study conclusion. Of the 19 patients who had a tremor at enrollment, 11 continued to exhibit a tremor at follow-up. Seven patients died after initial enrollment in the study, with 5 of those having presented in a coma. The factors that predict either severity or long-term recovery of neurological function include age (older individuals were weaker at follow-up examination), gender (males recovered better from coma), and presentation in a coma with cranial nerve deficits (had a poorer recovery particularly with regard to cognition).ConclusionsThis study represents one of the largest clinical investigations providing prospectively-acquired neurological outcomes data among American patients with WNV central nervous system disease. The findings show that the factors that influence prognosis from the initial presentation include age, gender, and specific neurological deficits at onset.Trial registrationClinicalTrials.gov identifier: NCT00138463 and NCT00069316.

Project description:Background: Neurological manifestations have increasingly become recognized in COVID-19. People from different ethnic backgrounds are experiencing different outcomes related to SARS-CoV-2 infection. Several cohort studies reported the common neurological manifestations and complications associated with COVID-19 disease around the world however, the prevalence of neurological complications associated with SARS-CoV-2 infection in the Arab countries and Saudi Arabia is still unknown. Objective: To study the prevalence, risk factors, and characteristics of the neurological complications associated with COVID-19 and their relationship with clinical outcomes. Methods: We conducted a prospective, single-center, observational, cohort study of consecutive hospitalized adults COVID-19 patients with and without neurological manifestation admitted between March 2020 until the end of December 2020. Data was collected prospectively using electronic medical records; Cases and controls were observed until they either get discharged from the hospital or died. The primary outcomes were death, survival, and survival with sequalae. Results: Among 497 patients with COVID-19, 118 patients (23.7%) had neurological complications, 94 patients (18.9%) had encephalopathy, and 16 patients (3.2%) had cerebrovascular accidents (CVA). Patients with COVID-19-related neurological complications were older and more likely to have a pre-existing neurological disease. The most common neurological syndrome associated with COVID-19 were encephalopathy (18.9%) and headache (13.7%). Pre-existing neurological disease and an elevated neutrophil count were the strongest predictors of developing any neurological complications. Death form COVID-19 was associated with age (OR 1.06, 95% CI 1.02-1.10, P = 0.001), invasive ventilation (OR 37.12, 95% CI 13.36-103.14), COVID-19-related-neurological complications (OR 3.24, 95% CI 1.28-8.21, P = 0.01), and elevated CRP level (OR 1.01, 95% CI 1.00-1.01, P = 0.01). Conclusions: COVID-19 is associated with a wide range of neurological manifestations in people living in Saudi Arabia, with older individuals and those with underlying neurological disorders being most at risk. The presence of neurological complications was associated with increased mortality and poor outcomes.

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Potential neuroinvasive pathways of SARS-CoV-2: Deciphering the spectrum of neurological deficit seen in coronavirus disease-2019 (COVID-19).

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