Central Nervous System Manifestations of COVID-19:

 
Central Nervous System Manifestations of COVID-19:
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Coronavirus is one of the major viruses that primarily targets the human respiratory system, but it also has neuroinvasivecapabilities and can spread from the respiratory tract to the central nervous system (CNS). Previous epidemics or pandemicsof coronaviruses include the severe acute respiratory syndrome (SARS) in 2002 and the Middle East respiratory syndrome (MERS)in 2012. The most recent pandemic of coronavirus infection is coronavirus disease (COVID-19)thatis caused by SARS-CoV21, 2. The symptoms of COVID-19 infection usually appear after an incubation period of about five days.

 The most common symptoms of COVID-19 illness are fever, cough, and fatigue; other symptoms include headache, hemoptysis,and dyspnea, among others. In the most severe cases, patients may develop pneumonia, acute respiratory distress syndrome, acute cardiac problems, and multiorgan failure1.The first cases of COVID-19 were reported in December 20191; however, when wesearched the MEDLINE (accessed from PubMed), from December 01, 2019to March 26, 2020, with the key word “COVID 19”, surprisingly 1655articles were yielded.This shows that COVID-19 pandemic is of great global public health concern

 

Coronavirus infections have beenassociated with neurological manifestations(e.g., febrile seizures, convulsions, change in mental status, and encephalitis)2, 3.Neurotropic andneuroinvasive capabilities of coronaviruses have been described in humans. Upon nasal infection, coronavirus enters the CNS through the olfactory bulb, causing inflammation and demyelination3. 

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Finally, patients with severe COVID-19 may have hypoxia, multiorgan failure, and metabolic and electrolyte derangements, and may require sophisticatedmedication regimens and therapeutic interventions. Hence, it is plausible to expect clinical or subclinical acute symptomatic seizures and status epilepticus to happen in these patients. Impaired mental status has been reported in patients with severe COVID-199, 14; but, this manifestation has never been studied appropriately in previous studies(Table 3). When visiting a patient who is in a critical medical conditionand has a change in mental status, one shouldmake sure that nonconvulsive status epilepticus (NCSE)is not a part of the clinical scenario.The diagnosis of NCSE is frequently overlooked, with patients in critical medical conditions having other serious problems.It is necessary to perform continuous EEG monitoring in any patient with acritical medical condition, who has achange in mental status,in order to make a timely diagnosis of NCSE19. Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus is a helpful guide to make a diagnosis of NCSE in critically ill patients

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While neurological manifestations of COVID-19have not been studied appropriatelyyet, it is highly likely that some of these patients, particularly those who suffer from a severe illness, have CNS involvement and neurological manifestations. Precise and targeted documentation Journal Pre-proofJournal Pre-proof
8of the neurological symptoms (e.g., headache, dizziness, etc.) and signs (e.g., change in mental status, meningeal signs, etc.), detailed clinical,neurological, and electrophysiologicalinvestigations(e.g., EEG)of the patients (particularly those with a change in mental status), attempts to isolate SARS-CoV-2 from CSF, and autopsies of the COVID-19 victimsmayclarify the rolesplayed by this virus in causing neurological manifestations. 

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References1.Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity 2020:102433.2.Desforges M, Le Coupanec A, Dubeau P, et al. Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Viruses 2020;12:14.3.Bohmwald K, Galvez N, Ríos M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Frontiers in cellular neuroscience 2018;12:386.4.Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Annals of internal medicine 2015;162:777-784.5.MoherD, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Annals of internal medicine 2009;151:264-269.6.Gronseth GS CJ, Gloss D, Merillat S, Dittman J, Armstrong MJ, et al. . on behalf of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. 2017. Clinical Practice Guideline Process Manual, 2017 ed. Minneapolis, MN: The American Academy of Neurology. 2017.7.Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. Journal of Medical Virology 2020.8.Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting theCNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms. ACS chemical neuroscience 2020.9.Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. https://www.medrxiv.org/content/10.1101/2020.02.22.20026500v1/accessed on April 4, 2020. This article is a preprint and has not been peer-reviewed.10.Li Y, Wang M, Zhou Y, et al. Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study. 2020.https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550025/accessed on April 4, 2020. This article is a preprint and has not been peer-reviewed. 11.Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020;395:497-506.12.Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine 2020.13.Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama 2020.14.Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 2020;395:507-513.15.Hung EC, Chim SS, Chan PK, et al. Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome. Clinical Chemistry 2003;49:2108-2109.16.Lau K-K, Yu W-C, Chu C-M, Lau S-T, Sheng B, Yuen K-Y. Possible central nervous system infection by SARS coronavirus. Emerging infecti