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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="review-article" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">IJCV</journal-id>
      <journal-title-group>
        <journal-title>International Journal of Coronaviruses</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2692-1537</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.14302/issn.2692-1537.ijcv-21-4007</article-id>
      <article-id pub-id-type="publisher-id">IJCV-21-4007</article-id>
      <article-categories>
        <subj-group>
          <subject>review-article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Impact of COVID-19 on Cognitive and Way to Resolve </article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Mohammad</surname>
            <given-names>Azizur Rahman</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842018420">1</xref>
          <xref ref-type="aff" rid="idm1842018996">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nabidur</surname>
            <given-names>Rahman</given-names>
          </name>
          <xref ref-type="aff" rid="idm1842018420">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1842018420">
        <label>1</label>
        <addr-line>Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh. </addr-line>
      </aff>
      <aff id="idm1842018996">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Raul</surname>
            <given-names>Isea</given-names>
          </name>
          <xref ref-type="aff" rid="idm1841886324">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1841886324">
        <label>1</label>
        <addr-line>Fundación Instituto de Estudios  Avanzados - IDEA, Hoyo de la Puerta, Baruta.</addr-line>
      </aff>
      <author-notes>
        <corresp>
  Mohammad Azizur Rahman, <addr-line>Department of                 Biochemistry and Molecular Biology,                        Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.</addr-line><email>azizbmb@juniv.edu</email></corresp>
        <fn fn-type="conflict" id="idm1842987148">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2021-11-20">
        <day>20</day>
        <month>11</month>
        <year>2021</year>
      </pub-date>
      <volume>3</volume>
      <issue>3</issue>
      <fpage>16</fpage>
      <lpage>19</lpage>
      <history>
        <date date-type="received">
          <day>30</day>
          <month>10</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>11</month>
          <year>2021</year>
        </date>
        <date date-type="online">
          <day>20</day>
          <month>11</month>
          <year>2021</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2021</copyright-year>
        <copyright-holder>Mohammad Azizur Rahman, et al.</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/ijcv/article/1730">This article is available from http://openaccesspub.org/ijcv/article/1730</self-uri>
      <abstract>
        <p>Cognitive abilities are of immense                  importance for the normal life sustenance of a    human being. As cognitive impairment ensues, the living caliber declines. Among multiple factors, the current epidemic coronavirus diseases 2019 (COVID-19) has been implicated in worsening  cognitive performance of the COVID-19 sufferers. Present article pinpoints the etiology and patho            physiology as well as recommendations to overcome the COVID-19 led cognitive decline.</p>
      </abstract>
      <kwd-group>
        <kwd>Alzheimer’s disease</kwd>
        <kwd>Cognition</kwd>
        <kwd>COVID-19</kwd>
        <kwd>Dementia</kwd>
        <kwd>SARS-CoV-2.</kwd>
      </kwd-group>
      <counts>
        <fig-count count="4"/>
        <table-count count="5"/>
        <page-count count="4"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1841881860" sec-type="intro">
      <title>Introduction</title>
      <p>Among the grave concerns of COVID-19, the cognitive issue is foremost. Most of the COVID-19 survivors are either sufferers of cognitive impairment or remain vulnerable to the same as their short- or long-term consequences. Thus, the reasons behind this impediment should be delved out and                  appropriate recommendations should be formulated to save the global innumerable populace. In this               context, the present study reports the cognitive               impairments of the COVID-19 sufferers, the                      etiopathology, pathomechanism and putative                   recommendations.</p>
    </sec>
    <sec id="idm1841883156">
      <title>Cognitive Performance</title>
      <p>Cognitive performance comprises a number of abilities, including but not limited to, attention and thinking, listening and understanding, viewing and judging, learning and memory, reasoning and               problem solving, justifying and decision making, as a whole, mental well being <xref ref-type="bibr" rid="ridm1842049892">1</xref>. Among different organs of the body, the central nervous system (CNS) is intricately linked with cognitive performance of a person <xref ref-type="bibr" rid="ridm1842051548">2</xref>. Any perturbation of the CNS affects the organismal cognitive performance <xref ref-type="bibr" rid="ridm1842051548">2</xref>. Though all of the cognitive attributes might not be affected equally, impairment of one type    influences other, albeit modifies the normalcy <xref ref-type="bibr" rid="ridm1842061708">3</xref>.                   Recently, this type of induced cognitive impairment have been noticed in the COVID-19 sufferers <xref ref-type="bibr" rid="ridm1842061708">3</xref>.</p>
      <sec id="idm1841881140">
        <title>COVID-19</title>
        <p>Epidemic coronavirus diseases 2019 (COVID-19) has taken a heavy toll worldwide. Caused by the severe acute respiratory distress syndrome coronavirus serotype 2 (SARS CoV-2), COVID-19 affects mainly the respiratory system <xref ref-type="bibr" rid="ridm1842130964">4</xref>. Unfortunately, the entry route of SARS CoV-2, the angiotensin converting enzyme 2 receptor (ACE2R), abounds in the CNS and is a haven for this virus <xref ref-type="bibr" rid="ridm1842130964">4</xref>.                   Consequently, the COVID-19 patients co-manifest CNS   abnormalities along with respiratory anomalies <xref ref-type="bibr" rid="ridm1842130964">4</xref>. As the CNS becomes affected, associated cognitive functions              become disrupted <xref ref-type="bibr" rid="ridm1842130964">4</xref>. In this way, the secondary                      complications of the COVID-19 patients has been the             deranged cognitive attributes that warrant adequate     withstanding and management strategy.</p>
      </sec>
      <sec id="idm1841881068">
        <title>COVID-19 and Deranged Cognition – the Achilles Heel</title>
        <p>The “brain fog”, manifested through cognitive  deficit are the etiological and patho-physiological                 resultants COVID-19. Following etiological and                      patho-physiological concerns could be attributed to this muddle.</p>
      </sec>
      <sec id="idm1841882076">
        <title>ACE2 Overexpression</title>
        <p>COVID-19 patients exhibit hyper expression of the ACE2 receptor that welcome the invading SARS-CoV-2 exceedingly <xref ref-type="bibr" rid="ridm1842130964">4</xref><xref ref-type="bibr" rid="ridm1841911332">5</xref>. Later on, pro-inflammatory cytokine led “cytokine storm” cripples both the respiratory system and CNS. Deranged CNS can hardly afford cognitive                            performance <xref ref-type="bibr" rid="ridm1842130964">4</xref><xref ref-type="bibr" rid="ridm1841911332">5</xref>. Shockingly, hippocampus and                        temporal lobes, the brain regions involved in memory and cognition, express ACE2 receptors that only worsen the cognitive level of the COVID-19 sufferers <xref ref-type="bibr" rid="ridm1842130964">4</xref><xref ref-type="bibr" rid="ridm1841911332">5</xref>.</p>
      </sec>
      <sec id="idm1841880420">
        <title>Neurotoxicity </title>
        <p>SARS-CoV-2 led direct neurotoxicity vandalize the neurogenesis, synaptic plasticity, neurotransmission that are the neuropsychiatric hallmarks of cognitive                         decline <xref ref-type="bibr" rid="ridm1842130964">4</xref><xref ref-type="bibr" rid="ridm1841911332">5</xref><xref ref-type="bibr" rid="ridm1841908956">6</xref>.</p>
      </sec>
      <sec id="idm1841880492">
        <title>Hypoxic-Ischemic Brain Injury </title>
        <p>Depleted supply of oxygen to the CNS due to               pulmonary debility attenuate CNS performance <xref ref-type="bibr" rid="ridm1841899324">7</xref><xref ref-type="bibr" rid="ridm1841893996">8</xref>.               Besides, cerebrovascular injury and bursting of                       pro-inflammatory cytokines scars the CNS. Also, ischemic brain damage and stroke are seminal hallmarks of                       dementia and cognitive impairment <xref ref-type="bibr" rid="ridm1841899324">7</xref><xref ref-type="bibr" rid="ridm1841893996">8</xref>.</p>
      </sec>
      <sec id="idm1841880708">
        <title>Neurovascular Dysfunction</title>
        <p>Blood brain barrier (BBB) and endothelial                   dysfunction leading to cerebral microvascular damage propensities SARS-CoV-2 malediction, otherwise                      accentuates cognitive malfunction <xref ref-type="bibr" rid="ridm1841893492">9</xref><xref ref-type="bibr" rid="ridm1841882836">10</xref>.  </p>
      </sec>
      <sec id="idm1841872668">
        <title>Co-Morbidity</title>
        <p>Cognitive decline in COVID-19 patients are                  co-morbid expression of multiple pathophysiological symptoms <xref ref-type="bibr" rid="ridm1841881036">11</xref>. Besides, pre-existing cognitive decline associated with dementia and Alzheimer’s disease (AD) had been found to be overly diminished in COVID-19                   sufferers <xref ref-type="bibr" rid="ridm1841857404">12</xref>. Diabetes and hypertenstion are among the modifiable co-morbidities of COVID-19 and cognitive                 decline. Alzheimer’s disease (AD), the most common form of dementia, has been reported to be interlinked with COVID-19 <xref ref-type="bibr" rid="ridm1841853228">14</xref><xref ref-type="bibr" rid="ridm1841847828">15</xref><xref ref-type="bibr" rid="ridm1841861580">16</xref><xref ref-type="bibr" rid="ridm1841839972">17</xref><xref ref-type="bibr" rid="ridm1841838676">18</xref>. </p>
      </sec>
    </sec>
    <sec id="idm1841873460">
      <title>Recommendations</title>
      <p>People suffering from cognitive impairments            during COVID-19 crises,</p>
      <p>1. should be checked through COVID-19 tests.</p>
      <p>2. should have adequate behavioral support.</p>
      <p>3. should be supplied with medication that minimizes the consequences of neurovascular injury.</p>
      <p>National and international health care                        professionals should formulate state of the art guidelines to lower the burden of cognitively impaired persons.</p>
    </sec>
    <sec id="idm1841873892" sec-type="conclusions">
      <title>Conclusion</title>
      <p>COVID-19 has plagued the global humanity,                 especially those who are already cognitively impaired. Even, <italic>de novo</italic> cognitive impairments have been detected among the COVID-19 sufferers. Immediate measures against COVID-19 led cognitive impairment could reduce global economic burden. Further studies are called for withstanding this global crisis.</p>
    </sec>
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