Central nervous system manifestations of COVID-19: A systematic review
Identifieur interne : 001844 ( Pmc/Corpus ); précédent : 001843; suivant : 001845Central nervous system manifestations of COVID-19: A systematic review
Auteurs : Ali A. Asadi-Pooya ; Leila SimaniSource :
- Journal of the Neurological Sciences [ 0022-510X ] ; 2020.
Abstract
In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19.
MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”.
Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general.
While neurological manifestations of COVID-19 have not been studied appropriately, 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 of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.
Url:
DOI: 10.1016/j.jns.2020.116832
PubMed: 32299017
PubMed Central: 7151535
Links to Exploration step
PMC:7151535Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Central nervous system manifestations of COVID-19: A systematic review</title><author><name sortKey="Asadi Pooya, Ali A" sort="Asadi Pooya, Ali A" uniqKey="Asadi Pooya A" first="Ali A." last="Asadi-Pooya">Ali A. Asadi-Pooya</name><affiliation><nlm:aff id="af0005">Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran</nlm:aff></affiliation><affiliation><nlm:aff id="af0010">Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, USA</nlm:aff></affiliation></author><author><name sortKey="Simani, Leila" sort="Simani, Leila" uniqKey="Simani L" first="Leila" last="Simani">Leila Simani</name><affiliation><nlm:aff id="af0015">Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti Univsersity of Medical Sciences, Tehran, Iran</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32299017</idno><idno type="pmc">7151535</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151535</idno><idno type="RBID">PMC:7151535</idno><idno type="doi">10.1016/j.jns.2020.116832</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001844</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001844</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Central nervous system manifestations of COVID-19: A systematic review</title><author><name sortKey="Asadi Pooya, Ali A" sort="Asadi Pooya, Ali A" uniqKey="Asadi Pooya A" first="Ali A." last="Asadi-Pooya">Ali A. Asadi-Pooya</name><affiliation><nlm:aff id="af0005">Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran</nlm:aff></affiliation><affiliation><nlm:aff id="af0010">Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, USA</nlm:aff></affiliation></author><author><name sortKey="Simani, Leila" sort="Simani, Leila" uniqKey="Simani L" first="Leila" last="Simani">Leila Simani</name><affiliation><nlm:aff id="af0015">Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti Univsersity of Medical Sciences, Tehran, Iran</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of the Neurological Sciences</title><idno type="ISSN">0022-510X</idno><idno type="eISSN">1878-5883</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective</title><p>In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19.</p></sec><sec><title>Methods</title><p>MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”.</p></sec><sec><title>Results</title><p>Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general.</p></sec><sec><title>Conclusion</title><p>While neurological manifestations of COVID-19 have not been studied appropriately, 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 of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Rothan, H A" uniqKey="Rothan H">H.A. Rothan</name></author><author><name sortKey="Byrareddy, S N" uniqKey="Byrareddy S">S.N. Byrareddy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Desforges, M" uniqKey="Desforges M">M. Desforges</name></author><author><name sortKey="Le Coupanec, A" uniqKey="Le Coupanec A">A. Le Coupanec</name></author><author><name sortKey="Dubeau, P" uniqKey="Dubeau P">P. Dubeau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bohmwald, K" uniqKey="Bohmwald K">K. Bohmwald</name></author><author><name sortKey="Galvez, N" uniqKey="Galvez N">N. Galvez</name></author><author><name sortKey="Rios, M" uniqKey="Rios M">M. Ríos</name></author><author><name sortKey="Kalergis, A M" uniqKey="Kalergis A">A.M. Kalergis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hutton, B" uniqKey="Hutton B">B. Hutton</name></author><author><name sortKey="Salanti, G" uniqKey="Salanti G">G. Salanti</name></author><author><name sortKey="Caldwell, D M" uniqKey="Caldwell D">D.M. Caldwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moher, D" uniqKey="Moher D">D. Moher</name></author><author><name sortKey="Liberati, A" uniqKey="Liberati A">A. Liberati</name></author><author><name sortKey="Tetzlaff, J" uniqKey="Tetzlaff J">J. Tetzlaff</name></author><author><name sortKey="Altman, D G" uniqKey="Altman D">D.G. Altman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gronseth, G S C J" uniqKey="Gronseth G">G.S.C.J. Gronseth</name></author><author><name sortKey="Gloss, D" uniqKey="Gloss D">D. Gloss</name></author><author><name sortKey="Merillat, S" uniqKey="Merillat S">S. Merillat</name></author><author><name sortKey="Dittman, J" uniqKey="Dittman J">J. Dittman</name></author><author><name sortKey="Armstrong, M J" uniqKey="Armstrong M">M.J. Armstrong</name></author><author><name sortKey="On Behalf Of The Guideline Development Dissemination And Implementation Subcommittee Of The American Academy Of Neurology" uniqKey="On Behalf Of The Guideline Development Dissemination And Implementation Subcommittee Of The American Academy Of Neurology">on behalf of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y C" uniqKey="Li Y">Y.C. Li</name></author><author><name sortKey="Bai, W Z" uniqKey="Bai W">W.Z. Bai</name></author><author><name sortKey="Hashikawa, T" uniqKey="Hashikawa T">T. Hashikawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baig, A M" uniqKey="Baig A">A.M. Baig</name></author><author><name sortKey="Khaleeq, A" uniqKey="Khaleeq A">A. Khaleeq</name></author><author><name sortKey="Ali, U" uniqKey="Ali U">U. Ali</name></author><author><name sortKey="Syeda, H" uniqKey="Syeda H">H. Syeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mao, L" uniqKey="Mao L">L. Mao</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Chen, S" uniqKey="Chen S">S. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C. Huang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Yu, Y" uniqKey="Yu Y">Y. Yu</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Hu, C" uniqKey="Hu C">C. Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, N" uniqKey="Chen N">N. Chen</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M. Zhou</name></author><author><name sortKey="Dong, X" uniqKey="Dong X">X. Dong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hung, E C" uniqKey="Hung E">E.C. Hung</name></author><author><name sortKey="Chim, S S" uniqKey="Chim S">S.S. Chim</name></author><author><name sortKey="Chan, P K" uniqKey="Chan P">P.K. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, K K" uniqKey="Lau K">K.-K. Lau</name></author><author><name sortKey="Yu, W C" uniqKey="Yu W">W.-C. Yu</name></author><author><name sortKey="Chu, C M" uniqKey="Chu C">C.-M. Chu</name></author><author><name sortKey="Lau, S T" uniqKey="Lau S">S.-T. Lau</name></author><author><name sortKey="Sheng, B" uniqKey="Sheng B">B. Sheng</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Fan, R" uniqKey="Fan R">R. Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saad, M" uniqKey="Saad M">M. Saad</name></author><author><name sortKey="Omrani, A S" uniqKey="Omrani A">A.S. Omrani</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K. Baig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mir, J M" uniqKey="Mir J">J.M. Miró</name></author><author><name sortKey="De Teran, F D" uniqKey="De Teran F">F.D. de Terán</name></author><author><name sortKey="Singer, P A" uniqKey="Singer P">P.A. Singer</name></author><author><name sortKey="Prior, M A A" uniqKey="Prior M">M.A.-A. Prior</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leitinger, M" uniqKey="Leitinger M">M. Leitinger</name></author><author><name sortKey="Beniczky, S" uniqKey="Beniczky S">S. Beniczky</name></author><author><name sortKey="Rohracher, A" uniqKey="Rohracher A">A. Rohracher</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Neurol Sci</journal-id><journal-id journal-id-type="iso-abbrev">J. Neurol. Sci</journal-id><journal-title-group><journal-title>Journal of the Neurological Sciences</journal-title></journal-title-group><issn pub-type="ppub">0022-510X</issn><issn pub-type="epub">1878-5883</issn><publisher><publisher-name>Elsevier B.V.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32299017</article-id><article-id pub-id-type="pmc">7151535</article-id><article-id pub-id-type="publisher-id">S0022-510X(20)30168-4</article-id><article-id pub-id-type="doi">10.1016/j.jns.2020.116832</article-id><article-id pub-id-type="publisher-id">116832</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Central nervous system manifestations of COVID-19: A systematic review</article-title></title-group><contrib-group><contrib contrib-type="author" id="au0005"><name><surname>Asadi-Pooya</surname><given-names>Ali A.</given-names></name><email>aliasadipooya@yahoo.com</email><xref rid="af0005" ref-type="aff">a</xref><xref rid="af0010" ref-type="aff">b</xref><xref rid="cr0005" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au0010"><name><surname>Simani</surname><given-names>Leila</given-names></name><xref rid="af0015" ref-type="aff">c</xref></contrib></contrib-group><aff id="af0005"><label>a</label>Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran</aff><aff id="af0010"><label>b</label>Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia, USA</aff><aff id="af0015"><label>c</label>Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti Univsersity of Medical Sciences, Tehran, Iran</aff><author-notes><corresp id="cr0005"><label>⁎</label>Corresponding author at: Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. <email>aliasadipooya@yahoo.com</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>11</day><month>4</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>15</day><month>6</month><year>2020</year></pub-date><pub-date pub-type="epub"><day>11</day><month>4</month><year>2020</year></pub-date><volume>413</volume><fpage>116832</fpage><lpage>116832</lpage><history><date date-type="received"><day>7</day><month>4</month><year>2020</year></date><date date-type="accepted"><day>8</day><month>4</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Elsevier B.V. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Elsevier B.V.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="ab0005"><sec><title>Objective</title><p>In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19.</p></sec><sec><title>Methods</title><p>MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”.</p></sec><sec><title>Results</title><p>Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general.</p></sec><sec><title>Conclusion</title><p>While neurological manifestations of COVID-19 have not been studied appropriately, 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 of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.</p></sec></abstract><abstract abstract-type="author-highlights" id="ab0010"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="li0005"><label>•</label><p id="p0005">Some patients with COVID-19 may show nonspecific neurological symptoms, such as confusion and headache.</p></list-item><list-item id="li0010"><label>•</label><p id="p0010">A few patients with COVID-19 showed more specific neurological manifestations, such as seizure or cerebrovascular problems.</p></list-item><list-item id="li0015"><label>•</label><p id="p0015">Neuroinvasion of SARS-CoV2 may partially explain why some patients develop respiratory failure.</p></list-item></list></p></abstract><kwd-group id="ks0005"><title>Keywords</title><kwd>CNS</kwd><kwd>Coronavirus</kwd><kwd>COVID-19</kwd><kwd>Neurological</kwd><kwd>Seizure</kwd></kwd-group></article-meta></front><body><sec id="s0005"><label>1</label><title>Introduction</title><p id="p0020">Coronavirus is one of the major viruses that primarily targets the human respiratory system, but it also has neuroinvasive capabilities and can spread from the respiratory tract to the central nervous system (CNS). Previous epidemics or pandemics of 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) that is caused by SARS-CoV2 [<xref rid="bb0005" ref-type="bibr">1</xref>,<xref rid="bb0010" ref-type="bibr">2</xref>]. 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 failure [<xref rid="bb0005" ref-type="bibr">1</xref>]. The first cases of COVID-19 were reported in December 2019 [<xref rid="bb0005" ref-type="bibr">1</xref>]; however, when we searched the MEDLINE (accessed from PubMed), from December 01, 2019 to March 26, 2020, with the key word “COVID 19”, surprisingly 1655 articles were yielded. This shows that COVID-19 pandemic is of great global public health concern.</p><p id="p0025">Coronavirus infections have been associated with neurological manifestations (e.g., febrile seizures, convulsions, change in mental status, and encephalitis) [<xref rid="bb0010" ref-type="bibr">2</xref>,<xref rid="bb0015" ref-type="bibr">3</xref>]. Neurotropic and neuroinvasive capabilities of coronaviruses have been described in humans. Upon nasal infection, coronavirus enters the CNS through the olfactory bulb, causing inflammation and demyelination [<xref rid="bb0015" ref-type="bibr">3</xref>]. In this systematic review, we will discuss the evidence on the occurrence of CNS involvement and neurological manifestations in patients with COVID-19.</p></sec><sec id="s0010"><label>2</label><title>Methods</title><p id="p0030">The report of this systematic review was made according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [<xref rid="bb0020" ref-type="bibr">4</xref>,<xref rid="bb0025" ref-type="bibr">5</xref>] (<xref rid="f0005" ref-type="fig">Fig. 1</xref>). The review protocol was not previously registered. MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”. Articles written in English were all included in this search. To ensure literature saturation, the authors scanned the reference lists of the included studies or relevant reviews identified through the search. Both authors participated through each phase of the review independently (screening, eligibility, and inclusion). They independently screened the titles and abstracts yielded by the search against the inclusion criteria. They obtained full reports for all titles that appeared to meet the inclusion criteria or where there was any uncertainty. Authors screened the full text reports and decided whether these meet the inclusion criteria. They resolved any disagreement through discussions. Neither of the authors were blind to the journal titles or to the study authors or institutions.<fig id="f0005"><label>Fig. 1</label><caption><p>Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram of the study.</p></caption><alt-text id="al0005">Fig. 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="p0035">The following data were extracted from the included studies: study authors, study designs, main results, and limitations. The methodological quality of the included studies was assessed by the authors. The class of evidence was defined following the American Academy of Neurology criteria for classification of evidence in studies of causation (Appendix 1) [<xref rid="bb0030" ref-type="bibr">6</xref>].</p><sec id="s0015"><label>2.1</label><title>Standard protocol approvals, registrations, and patient consents</title><p id="p0040">The Shiraz University of Medical Sciences Institutional Review Board approved this systematic review.</p></sec></sec><sec id="s0020"><label>3</label><title>Results</title><p id="p0045">Through the search strategy, we could identify two articles about neurological involvement by COVID-19 (<xref rid="t0005" ref-type="table">Table 1</xref>, <xref rid="t0010" ref-type="table">Table 2</xref>) [<xref rid="bb0035" ref-type="bibr">7</xref>,<xref rid="bb0040" ref-type="bibr">8</xref>]. One of these publications was a narrative review [<xref rid="bb0035" ref-type="bibr">7</xref>] and the other one was a viewpoint [<xref rid="bb0040" ref-type="bibr">8</xref>]. However, to ensure literature saturation, the authors scanned the reference lists of the included studies and could identify multiple references [9–14]. <xref rid="t0015" ref-type="table">Table 3</xref>shows the summary of these studies on the CNS manifestations of COVID-19. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients [<xref rid="bb0045" ref-type="bibr">9</xref>]. However, the authors did not perform electroencephalography (EEG) or cerebrospinal fluid (CSF) analysis. Another retrospective study investigated acute cerebrovascular disease occurrence following COVID-19 [<xref rid="bb0050" ref-type="bibr">10</xref>]. Other studies investigated the manifestations of COVID-19 in general; they did not specifically pay attention to the neurological manifestations [<xref rid="bb0055" ref-type="bibr">[11]</xref>, <xref rid="bb0060" ref-type="bibr">[12]</xref>, <xref rid="bb0065" ref-type="bibr">[13]</xref>, <xref rid="bb0070" ref-type="bibr">[14]</xref>].<table-wrap position="float" id="t0005"><label>Table 1</label><caption><p>The search keywords included “COVID 19” and those in the first column of the table.</p></caption><alt-text id="al0010">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th><hr></hr></th><th colspan="2">Medline (PubMed)<hr></hr></th><th colspan="2">Scopus (Article title, Abstract, Keywords)<hr></hr></th></tr><tr><th>Keywords</th><th>Primary hints</th><th>Relevant articles</th><th>Primary hints</th><th>Relevant articles</th></tr></thead><tbody><tr><td>Brain</td><td>17</td><td>0</td><td>2</td><td>1 (duplicate)</td></tr><tr><td>Neurologic</td><td>1</td><td>1</td><td>1</td><td>1 (duplicate)</td></tr><tr><td>CNS</td><td>1</td><td>1</td><td>0</td><td>0</td></tr><tr><td><bold>Total</bold></td><td><bold>19</bold></td><td><bold>2</bold></td><td><bold>3</bold></td><td><bold>2 (2 duplicates)</bold></td></tr></tbody></table></table-wrap><table-wrap position="float" id="t0010"><label>Table 2</label><caption><p>The search keywords included “coronavirus” and those in the first column of the table.</p></caption><alt-text id="al0015">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th><hr></hr></th><th colspan="2">Medline (PubMed)<hr></hr></th><th colspan="2">Scopus (Article title, Abstract, Keywords)<hr></hr></th></tr><tr><th>Keywords</th><th>Primary hints</th><th>Relevant articles</th><th>Primary hints</th><th>Relevant articles</th></tr></thead><tbody><tr><td>Brain</td><td>22</td><td>2 (2 duplicates)</td><td>9</td><td>1 (duplicate)</td></tr><tr><td>Neurologic</td><td>1</td><td>1 (duplicate)</td><td>4</td><td>1 (duplicate)</td></tr><tr><td>CNS</td><td>4</td><td>1 (duplicate)</td><td>3</td><td>0</td></tr><tr><td><bold>Total</bold></td><td><bold>27</bold></td><td><bold>4 (4 duplicates)</bold></td><td><bold>16</bold></td><td><bold>2 (2 duplicates)</bold></td></tr></tbody></table></table-wrap><table-wrap position="float" id="t0015"><label>Table 3</label><caption><p>Neurological manifestations of COVID-19.</p></caption><alt-text id="al0020">Table 3</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Author/year</th><th>Methods</th><th>Neurological manifestations</th><th>Limitations</th><th>Level of evidence</th></tr></thead><tbody><tr><td>Mao/ 2020 [<xref rid="bb0045" ref-type="bibr">9</xref>]</td><td>Retrospective case series of 214 admitted patients</td><td>CNS manifestations: in 25%. Headache (13%), dizziness (17%), impaired consciousness (8%), acute cerebrovascular problems (3%), ataxia (0.5), and seizures (0.5%)</td><td>No CSF analysis; no EEG study; no clear definition of symptoms</td><td>III</td></tr><tr><td>Li/ 2020 [<xref rid="bb0050" ref-type="bibr">10</xref>]</td><td>Retrospective case series of 221 admitted patients</td><td>5% developed acute ischemic stroke, 0.5% had cerebral venous sinus thrombosis, and 0.5% had cerebral hemorrhage</td><td>Other related neurological manifestations were not studied.</td><td>II</td></tr><tr><td>Huang/ 2020 [<xref rid="bb0055" ref-type="bibr">11</xref>]</td><td>Prospective study of 41 admitted patients</td><td>Headache in 8%</td><td>Not specifically studied neurological manifestations. No CSF or EEG studies</td><td>I</td></tr><tr><td>Yang/ 2020 [<xref rid="bb0060" ref-type="bibr">12</xref>]</td><td>Retrospective study of 52 critically ill adult patients</td><td>Headache in 6%</td><td>Not specifically studied neurological manifestations. No CSF or EEG studies</td><td>II</td></tr><tr><td>Wang/ 2020 [<xref rid="bb0065" ref-type="bibr">13</xref>]</td><td>Retrospective case series of the 138 hospitalized patients</td><td>Dizziness in 9%; Headache in 7%</td><td>Not specifically studied neurological manifestations. No CSF or EEG studies</td><td>II</td></tr><tr><td>Chen/ 2020 [<xref rid="bb0070" ref-type="bibr">14</xref>]</td><td>Retrospective case series of the 99 hospitalized patients</td><td>Confusion in 9%; Headache in 8%</td><td>Not specifically studied neurological manifestations. No CSF or EEG studies</td><td>II</td></tr></tbody></table><table-wrap-foot><fn><p>CNS: central nervous system; CSF: cerebrospinal fluid; EEG: electroencephalography.</p></fn></table-wrap-foot></table-wrap></p></sec><sec id="s0025"><label>4</label><title>Discussion</title><p id="p0050">In this study, we observed that the evidence on the CNS involvement and neurological manifestations of COVID-19 is scarce and of low quality. However, the only study that specifically investigated this issue documented that one-quarter of the hospitalized patients with a confirmed diagnosis of severe acute respiratory syndrome from coronavirus 2 infection had some manifestations of CNS involvement [<xref rid="bb0045" ref-type="bibr">9</xref>]. Some patients with COVID-19 may show nonspecific neurological symptoms, such as confusion and headache. A few patients with COVID-19 showed more specific neurological manifestations, such as seizure or cerebrovascular problems (<xref rid="t0015" ref-type="table">Table 3</xref>). Furthermore, neuroinvasion of SARS-CoV2 may partially explain why some patients develop respiratory failure, while others do not [<xref rid="bb0035" ref-type="bibr">7</xref>].</p><p id="p0055">Most coronaviruses share similar viral structures and infection pathways; hence, the pathomechanisms previously found for other coronaviruses may also be applicable for SARS-CoV2. Human coronaviruses are not always confined to the respiratory tract; they can invade the CNS. A growing body of evidence shows that neuroinvasion and neurotropism is a common feature of human coronaviruses [<xref rid="bb0010" ref-type="bibr">2</xref>]. Infection with SARS-CoV has been associated with neurological manifestations. In the reported patients with SARS-CoV, CSF tested positive for the virus [<xref rid="bb0075" ref-type="bibr">15</xref>,<xref rid="bb0080" ref-type="bibr">16</xref>]. In one study of 183 hospitalized children with clinically suspected acute encephalitis, 22 (12%) had coronavirus infection (type was not specified) by detection of anti-CoV IgM [<xref rid="bb0085" ref-type="bibr">17</xref>]. In a study of 70 patients with MERS-CoV infection, altered mental status was reported in 26% of the patients and 9% of the people had seizure [<xref rid="bb0090" ref-type="bibr">18</xref>]. Therefore, it is very likely to observe neurological manifestations in patients with COVID-19 if we carefully and specifically look for them.</p><p id="p0060">Finally, patients with severe COVID-19 may have hypoxia, multiorgan failure, and metabolic and electrolyte derangements, and may require sophisticated medication 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-19 [9, 14]; but, this manifestation has never been studied appropriately in previous studies (<xref rid="t0015" ref-type="table">Table 3</xref>). When visiting a patient who is in a critical medical condition and has a change in mental status, one should make 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 a critical medical condition, who has a change in mental status, in order to make a timely diagnosis of NCSE [<xref rid="bb0095" ref-type="bibr">19</xref>]. Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus is a helpful guide to make a diagnosis of NCSE in critically ill patients [<xref rid="bb0100" ref-type="bibr">20</xref>].</p></sec><sec id="s0030"><label>5</label><title>Conclusion</title><p id="p0065">While neurological manifestations of COVID-19 have not been studied appropriately yet, 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 of the neurological symptoms (e.g., headache, dizziness, etc.) and signs (e.g., change in mental status, meningeal signs, etc.), detailed clinical, neurological, and electrophysiological investigations (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 victims may clarify the roles played by this virus in causing neurological manifestations.</p></sec></body><back><ref-list id="bi0005"><title>References</title><ref id="bb0005"><label>1</label><element-citation publication-type="journal" id="rf0005"><person-group person-group-type="author"><name><surname>Rothan</surname><given-names>H.A.</given-names></name><name><surname>Byrareddy</surname><given-names>S.N.</given-names></name></person-group><article-title>The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak</article-title><source>J. Autoimmun.</source><volume>102433</volume><year>2020</year></element-citation></ref><ref id="bb0010"><label>2</label><element-citation publication-type="journal" id="rf0010"><person-group person-group-type="author"><name><surname>Desforges</surname><given-names>M.</given-names></name><name><surname>Le Coupanec</surname><given-names>A.</given-names></name><name><surname>Dubeau</surname><given-names>P.</given-names></name></person-group><article-title>Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system?</article-title><source>Viruses</source><volume>12</volume><year>2020</year><fpage>14</fpage></element-citation></ref><ref id="bb0015"><label>3</label><element-citation publication-type="journal" id="rf0015"><person-group person-group-type="author"><name><surname>Bohmwald</surname><given-names>K.</given-names></name><name><surname>Galvez</surname><given-names>N.</given-names></name><name><surname>Ríos</surname><given-names>M.</given-names></name><name><surname>Kalergis</surname><given-names>A.M.</given-names></name></person-group><article-title>Neurologic alterations due to respiratory virus infections</article-title><source>Front. Cell. Neurosci.</source><volume>12</volume><year>2018</year><fpage>386</fpage><pub-id pub-id-type="pmid">30416428</pub-id></element-citation></ref><ref id="bb0020"><label>4</label><element-citation publication-type="journal" id="rf0020"><person-group person-group-type="author"><name><surname>Hutton</surname><given-names>B.</given-names></name><name><surname>Salanti</surname><given-names>G.</given-names></name><name><surname>Caldwell</surname><given-names>D.M.</given-names></name></person-group><article-title>The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations</article-title><source>Ann. Intern. Med.</source><volume>162</volume><year>2015</year><fpage>777</fpage><lpage>784</lpage><pub-id pub-id-type="pmid">26030634</pub-id></element-citation></ref><ref id="bb0025"><label>5</label><element-citation publication-type="journal" id="rf0025"><person-group person-group-type="author"><name><surname>Moher</surname><given-names>D.</given-names></name><name><surname>Liberati</surname><given-names>A.</given-names></name><name><surname>Tetzlaff</surname><given-names>J.</given-names></name><name><surname>Altman</surname><given-names>D.G.</given-names></name></person-group><article-title>Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement</article-title><source>Ann. Intern. Med.</source><volume>151</volume><year>2009</year><fpage>264</fpage><lpage>269</lpage><pub-id pub-id-type="pmid">19622511</pub-id></element-citation></ref><ref id="bb0030"><label>6</label><element-citation publication-type="book" id="rf0030"><person-group person-group-type="author"><name><surname>Gronseth</surname><given-names>G.S.C.J.</given-names></name><name><surname>Gloss</surname><given-names>D.</given-names></name><name><surname>Merillat</surname><given-names>S.</given-names></name><name><surname>Dittman</surname><given-names>J.</given-names></name><name><surname>Armstrong</surname><given-names>M.J.</given-names></name><name><surname>on behalf of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology</surname></name></person-group><chapter-title>Clinical Practice Guideline Process Manual</chapter-title><edition>2017 ed.</edition><year>2017</year><publisher-name>The American Academy of Neurology</publisher-name><publisher-loc>Minneapolis, MN</publisher-loc><fpage>2017</fpage></element-citation></ref><ref id="bb0035"><label>7</label><element-citation publication-type="journal" id="rf0035"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Y.C.</given-names></name><name><surname>Bai</surname><given-names>W.Z.</given-names></name><name><surname>Hashikawa</surname><given-names>T.</given-names></name></person-group><article-title>The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients</article-title><source>J. Med. Virol.</source><year>2020 Feb 27</year><comment>In press</comment></element-citation></ref><ref id="bb0040"><label>8</label><element-citation publication-type="journal" id="rf0040"><person-group person-group-type="author"><name><surname>Baig</surname><given-names>A.M.</given-names></name><name><surname>Khaleeq</surname><given-names>A.</given-names></name><name><surname>Ali</surname><given-names>U.</given-names></name><name><surname>Syeda</surname><given-names>H.</given-names></name></person-group><article-title>Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host–virus interaction, and proposed neurotropic mechanisms</article-title><source>ACS Chem. Neurosci.</source><volume>11</volume><issue>7</issue><year>2020</year><fpage>995</fpage><lpage>998</lpage><pub-id pub-id-type="pmid">32167747</pub-id></element-citation></ref><ref id="bb0045"><label>9</label><element-citation publication-type="other" id="rf0045"><person-group person-group-type="author"><name><surname>Mao</surname><given-names>L.</given-names></name><name><surname>Wang</surname><given-names>M.</given-names></name><name><surname>Chen</surname><given-names>S.</given-names></name></person-group><article-title>Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a Retrospective Case Series Study</article-title><ext-link ext-link-type="uri" xlink:href="https://www.medrxiv.org/content/10.1101/2020.02.22.20026500v1/" id="ir0005">https://www.medrxiv.org/content/10.1101/2020.02.22.20026500v1/</ext-link></element-citation></ref><ref id="bb0050"><label>10</label><element-citation publication-type="other" id="rf0050"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>M.</given-names></name><name><surname>Zhou</surname><given-names>Y.</given-names></name></person-group><article-title>Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study</article-title><ext-link ext-link-type="uri" xlink:href="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550025/" id="ir0010">https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550025/</ext-link><year>2020</year></element-citation></ref><ref id="bb0055"><label>11</label><element-citation publication-type="journal" id="rf0055"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>C.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name></person-group><article-title>Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China</article-title><source>Lancet</source><volume>395</volume><year>2020</year><fpage>497</fpage><lpage>506</lpage><pub-id pub-id-type="pmid">31986264</pub-id></element-citation></ref><ref id="bb0060"><label>12</label><element-citation publication-type="journal" id="rf0060"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>X.</given-names></name><name><surname>Yu</surname><given-names>Y.</given-names></name><name><surname>Xu</surname><given-names>J.</given-names></name></person-group><article-title>Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study</article-title><source>Lancet Respir. Med.</source><year>2020 Feb 24</year><comment>pii: S2213-2600(20)30079-5. In press</comment></element-citation></ref><ref id="bb0065"><label>13</label><element-citation publication-type="journal" id="rf0065"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>D.</given-names></name><name><surname>Hu</surname><given-names>B.</given-names></name><name><surname>Hu</surname><given-names>C.</given-names></name></person-group><article-title>Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China</article-title><source>Jama</source><year>2020 Feb 7</year><comment>In press</comment></element-citation></ref><ref id="bb0070"><label>14</label><element-citation publication-type="journal" id="rf0070"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>N.</given-names></name><name><surname>Zhou</surname><given-names>M.</given-names></name><name><surname>Dong</surname><given-names>X.</given-names></name></person-group><article-title>Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study</article-title><source>Lancet</source><volume>395</volume><year>2020</year><fpage>507</fpage><lpage>513</lpage><pub-id pub-id-type="pmid">32007143</pub-id></element-citation></ref><ref id="bb0075"><label>15</label><element-citation publication-type="journal" id="rf0075"><person-group person-group-type="author"><name><surname>Hung</surname><given-names>E.C.</given-names></name><name><surname>Chim</surname><given-names>S.S.</given-names></name><name><surname>Chan</surname><given-names>P.K.</given-names></name></person-group><article-title>Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome</article-title><source>Clin. Chem.</source><volume>49</volume><year>2003</year><fpage>2108</fpage><lpage>2109</lpage><pub-id pub-id-type="pmid">14633896</pub-id></element-citation></ref><ref id="bb0080"><label>16</label><element-citation publication-type="journal" id="rf0080"><person-group person-group-type="author"><name><surname>Lau</surname><given-names>K.-K.</given-names></name><name><surname>Yu</surname><given-names>W.-C.</given-names></name><name><surname>Chu</surname><given-names>C.-M.</given-names></name><name><surname>Lau</surname><given-names>S.-T.</given-names></name><name><surname>Sheng</surname><given-names>B.</given-names></name><name><surname>Yuen</surname><given-names>K.-Y.</given-names></name></person-group><article-title>Possible central nervous system infection by SARS coronavirus</article-title><source>Emerg. Infect. Dis.</source><volume>10</volume><year>2004</year><fpage>342</fpage><pub-id pub-id-type="pmid">15030709</pub-id></element-citation></ref><ref id="bb0085"><label>17</label><element-citation publication-type="journal" id="rf0085"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>H.</given-names></name><name><surname>Fan</surname><given-names>R.</given-names></name></person-group><article-title>Coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children</article-title><source>Intervirology</source><volume>59</volume><year>2016</year><fpage>163</fpage><lpage>169</lpage><pub-id pub-id-type="pmid">28103598</pub-id></element-citation></ref><ref id="bb0090"><label>18</label><element-citation publication-type="journal" id="rf0090"><person-group person-group-type="author"><name><surname>Saad</surname><given-names>M.</given-names></name><name><surname>Omrani</surname><given-names>A.S.</given-names></name><name><surname>Baig</surname><given-names>K.</given-names></name></person-group><article-title>Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia</article-title><source>Int. J. Infect. Dis.</source><volume>29</volume><year>2014</year><fpage>301</fpage><lpage>306</lpage><pub-id pub-id-type="pmid">25303830</pub-id></element-citation></ref><ref id="bb0095"><label>19</label><element-citation publication-type="journal" id="rf0095"><person-group person-group-type="author"><name><surname>Miró</surname><given-names>J.M.</given-names></name><name><surname>de Terán</surname><given-names>F.D.</given-names></name><name><surname>Singer</surname><given-names>P.A.</given-names></name><name><surname>Prior</surname><given-names>M.A.-A.</given-names></name></person-group><article-title>Emergency electroencephalogram: Usefulness in the diagnosis of nonconvulsive status epilepticus by the on-call neurologist</article-title><source>Neurología (English Edn)</source><volume>33</volume><year>2018</year><fpage>71</fpage><lpage>77</lpage></element-citation></ref><ref id="bb0100"><label>20</label><element-citation publication-type="journal" id="rf0100"><person-group person-group-type="author"><name><surname>Leitinger</surname><given-names>M.</given-names></name><name><surname>Beniczky</surname><given-names>S.</given-names></name><name><surname>Rohracher</surname><given-names>A.</given-names></name></person-group><article-title>Salzburg consensus criteria for non-convulsive status epilepticus–approach to clinical application</article-title><source>Epilepsy Behav.</source><volume>49</volume><year>2015</year><fpage>158</fpage><lpage>163</lpage><pub-id pub-id-type="pmid">26092326</pub-id></element-citation></ref></ref-list><ack id="ac0005"><sec id="s0035"><title>Acknowledgment</title><p id="p0070"><funding-source id="gts0005">Shiraz University of Medical Sciences</funding-source> supported this study.</p></sec><sec id="s0040"><title>Disclosures</title><p id="p0075">Ali A. Asadi-Pooya, M.D.: Honoraria from Cobel Daruo, RaymandRad and Tekaje; Royalty: Oxford University Press (Book publication). Leila Simani, PhD.: none.</p></sec></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001844 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001844 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:7151535
|texte= Central nervous system manifestations of COVID-19: A systematic review
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:32299017" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |