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  <front>
    <journal-meta id="journal-meta-690f9e70948d456a859b39fd8bb16530">
      <journal-id journal-id-type="nlm-ta">Sciresol</journal-id>
      <journal-id journal-id-type="publisher-id">Sciresol</journal-id>
      <journal-id journal-id-type="journal_submission_guidelines">https://www.jcbsonline.ac.in/</journal-id>
      <journal-title-group>
        <journal-title>Journal of Clinical and Biomedical Sciences</journal-title>
      </journal-title-group>
      <issn publication-format="electronic">2319-2453</issn>
      <issn publication-format="print"/>
    </journal-meta>
    <article-meta id="article-meta-2600bef623a34941b6ffd3b6b6c004d8">
      <article-id pub-id-type="doi">10.58739/jcbs/v15i3.25.35</article-id>
      <article-categories>
        <subj-group>
          <subject>ORIGINAL ARTICLE</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title id="article-title-1cf5792456814a228b26a71813793b11">
          <bold id="strong-4c6cc1e2f59d4a1f9b27525256cbdb7e">Peripheral Blood Smear Cell Morphology in COVID-19 </bold>
          <bold id="strong-16fd8cd88f674e15b2f55c7a829a14ba">Cases – </bold>
          <bold id="strong-58cd4923ab3e408c9781ddd6ee825792">A Cross </bold>
          <bold id="strong-25a0c9e19f9347d78241166135362cca">Sectional Study</bold>
        </article-title>
        <alt-title alt-title-type="right-running-head">Peripheral blood smear cell morphology in COVID-19 cases</alt-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name id="name-d4a973f188b84121b290bc068ec3df07">
            <surname>Reddy</surname>
            <given-names>Yeduguri Jahnavi</given-names>
          </name>
          <xref id="xref-38e5db776baa4327aa68a377f04edf69" rid="aff-2068380328e34732906af3c8bed7d948" ref-type="aff">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="yes">
          <name id="name-e3252fd69a014b70b21e46f9c2b4fb6f">
            <surname>Kalyani</surname>
            <given-names>R R</given-names>
          </name>
          <email>drkalyanir@rediffmail.com</email>
          <xref id="xref-f08d0d9c52bc4dd5b6948fa6553556f7" rid="aff-9cd94ae7580248d1a94066e815767500" ref-type="aff">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name id="name-a69deb05eca14c4aa5d7215189aa77d3">
            <surname>Prabhakar</surname>
            <given-names>K</given-names>
          </name>
          <xref id="xref-e914c61a3a49453182c58d470470795a" rid="aff-05cd603e41b64ac1b8ff64ece4643579" ref-type="aff">3</xref>
        </contrib>
        <aff id="aff-2068380328e34732906af3c8bed7d948">
          <institution>Senior Resident, Pathology, SDUMC</institution>
          <addr-line>Kolar, Karnataka</addr-line>
          <country country="IN">India</country>
        </aff>
        <aff id="aff-9cd94ae7580248d1a94066e815767500">
          <institution>Head and Director, R &amp; D, SDUMC</institution>
          <addr-line>Kolar, Karnataka </addr-line>
          <country country="IN">India</country>
        </aff>
        <aff id="aff-05cd603e41b64ac1b8ff64ece4643579">
          <institution>Dean and Principal, SDUMC</institution>
          <addr-line>Kolar , Karnataka</addr-line>
          <country country="IN">India</country>
        </aff>
      </contrib-group>
      <pub-date date-type="pub">
        <day>26</day>
        <month>9</month>
        <year>2025</year>
      </pub-date>
      <volume>15</volume>
      <issue>3</issue>
      <fpage>218</fpage>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>5</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>12</day>
          <month>6</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <copyright-year>2025</copyright-year>
      </permissions>
      <abstract id="abstract-abstract-title-542b37be66584c88ba2c2c798edd8adc">
        <title id="abstract-title-542b37be66584c88ba2c2c798edd8adc">Abstract</title>
        <p id="paragraph-af9793154ef644129a2811da32c40ea7"><bold id="strong-0cb4c78bcd8545aa9d6e88ec5e8d0e3a">Background:</bold><bold id="strong-87423e46fbd842dc88e921bddee115d1"> </bold>Coronavirus disease 2019 (COVID-19) is a newly diagnosed viral disease first identified China in December 2019 .The primary route of infection is by respiratory droplets and aerosols which enters into the cell. The lethal effects are due to the activation of renin angiotensin aldosterone pathway in the cell which further activates immune system and presents as lymphopenia in cases which have severe viral load. A few studies are available in English literature regarding quantitative parameters of peripheral blood, but very minimal data is available regarding morphological changes in blood smear. Hence this study was taken up to study morphological changes in the peripheral smears of patients with Covid-19.<bold id="strong-21ace3a5bb5242eeaaa895140451f47d"> </bold><bold id="strong-f1f1ae18d4cb49deb18f195b1c213b78">Objectives:</bold> To evaluate peripheral blood smears cell morphology in RT PCR confirmed cases of Covid19.<bold id="strong-0d36553b2f5e4a15ae709daac020d4b8"> </bold><bold id="strong-6d2fda55931d4a7bb3d94aa085aa1b5f">Materials and Methods:</bold><bold id="strong-7e8efbe5a8424767a85525af9b2beeb1"> </bold>All the cases were studied for a period of 3 months (May, June, July 2021) at Central Diagnostic Laboratory Services, RLJ Hospital, SDUMC, Kolar, Karnataka. Peripheral blood smears were made from all the blood samples which were collected in EDTA vacutainers, stained with Leishman stain and studied for morphological features of all three cell lines in the smear. Individual morphologies were noted.<bold id="strong-2337bfa003d94bee865de0d45e0f5da3"> </bold><bold id="strong-4444610b78a14911bac404885b81bea9">Results:</bold><bold id="strong-6c8ed4b705ad4f889787766e04e74afe"> </bold>Majority of the smears showed neutrophilia and lymphopenia with shift to left of neutrophilis. The morphological features seen in WBC’s in neutrophilis are hypersegmentation, monolobulated neutrophils, band forms, pyknotic nucleus, ring, fetal forms, toxic granules and cytoplasmic vacuoles.<bold id="strong-712e88ae23ea41edbcc811efa7294437"> </bold><bold id="strong-210f089efc064ea799fd290c08c2fc41">Conclusion:</bold><bold id="strong-c6e41c8b4b2242e7adfb259eff277c41"> </bold>Our study identifies and describes significant morphologic changes in the peripheral blood cells of COVID 19 patients.<sup id="superscript-4f9c74db1c2d481c9320b2d2523289bb"> </sup>An understanding of these morphologic changes in addition to established hematologic parameters can aid in the diagnosis of COVID-19. Peripheral smear review may help with management decisions in COVID-19 patients.</p>
      </abstract>
      <kwd-group id="kwd-group-6ee5532fe53c48389a2b2461b347ea21">
        <title>Keywords</title>
        <kwd>Covid-19</kwd>
        <kwd>Peripheral blood smear</kwd>
        <kwd>Morphological Changes</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement>None</funding-statement>
      </funding-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title id="title-fe19dba198854d64855dafa7c85f6142">1 Introduction</title>
      <p id="paragraph-3388ebcf97ae41259c954863cc6a39eb">Coronavirus disease 2019 (COVID-19) is a newly diagnosed viral disease first identified China in December 2019.<xref rid="R279374233846717" ref-type="bibr">1</xref>, <xref rid="R279374233846721" ref-type="bibr">2</xref> This virus transmits primarily through respiratory droplets and aerosols which enters into the cell by its interaction with angiotensin converting enzyme 2 (AEC 2) which is seen on surface of many cells such as endothelial cells and epithelial cells which lines capillaries and respiratory tract respectively. <xref rid="R279374233846721" ref-type="bibr">2</xref>, <xref rid="R279374233846725" ref-type="bibr">3</xref> The lethal effects are due to the activation of renin angiotensin aldosterone pathway in the cell which further activates immune system. <xref id="xref-e7110a0a9bdc47c09779c5f9850027f5" rid="R279374233846730" ref-type="bibr">4</xref></p>
      <p id="paragraph-c29c735f081a4bbeb712f6fe3a85732e">As the immune system gets activated, it presents as lymphopenia especially in in severe cases. Many studies are done regarding the quantitative parameters of peripheral blood but very little literature is available regarding the morphologic abnormalities in peripheral blood cells. <xref rid="R279374233846719" ref-type="bibr">5</xref>, <xref rid="R279374233846720" ref-type="bibr">6</xref>, <xref rid="R279374233846724" ref-type="bibr">7</xref> Identifying the various morphological patterns and changes in the blood can aid in diagnosis and treatment of patient. <xref id="xref-0bc82f61e5ee4540bd8f4a3aaeaf7e2e" rid="R279374233846718" ref-type="bibr">8</xref></p>
    </sec>
    <sec>
      <title id="title-f4845de75f8049f1bd41fdc6e9c97759">2 Materials and Methods</title>
      <p id="paragraph-dff61b87d2c4483bbbe80402b84a8434">This study was done in hematology laboratory of Pathology department after obtaining ethical clearance to start the study. All the blood samples of RT-PCR confirmed cases of Covid 19 were considered for peripheral smear examination. The smears were made and stained with Leishman stain and studied under microscope for various morphological changes in all the three cell lines- erythrocytes, leukocytes and platelets. 89 blood samples were collected over a period of 3 months (May, June, July 2021). Individual morphologies were noted.</p>
    </sec>
    <sec>
      <title id="title-a366eb7f42824a54b43f225772571228">3 Results</title>
      <p id="paragraph-84978fa6d87342a9a73595f88a892bf6">Of the 89 patients, 30 were females and 59 males. </p>
      <fig id="figure-14c4b3cefc5b4d2c85d3c33418d8059e" orientation="portrait" fig-type="graphic" position="anchor">
        <label>Figure 0 </label>
        <graphic id="graphic-315cc442e99947b3ac6059239ea9a3de" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage1.png"/>
      </fig>
      <sec>
        <title id="t-d04dfae02f29">3.1 <bold id="strong-4fb2cc5789f44c02b1fa1b0cf4beec67">Neutrophils</bold></title>
        <p id="paragraph-c211b573918b486388c418f574ae18d9">Neutrophils predominantly showed toxic granules and cytoplasmic vacuoles. Nuclear morphology showed various forms as hypersegmented forms, fetal shaped, monolobated, karyolysis, pyknotic nucleus. Neutrophils show immature forms with shift to left with band forms.</p>
        <fig id="figure-f6e9b331d7724ac3a852dbfef9a9da07" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 1 </label>
          <caption id="caption-c7720d4213404f4eaa9a9e2f368377c8">
            <title id="title-b581d76c16df4aeaba292e13b0e14880"/>
          </caption>
          <graphic id="graphic-d9bc7d2a10e94735a2f8f73a596a48f1" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage2.png"/>
        </fig>
        <fig id="figure-47fd023678d2478f9f8d8d035d2999a9" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 2 </label>
          <caption id="caption-8e91c9d4c35e469285fc8b7b710a9cf7">
            <title id="title-87d00f067500478ea1012712d0b274e7"/>
          </caption>
          <graphic id="graphic-f7d725b04c3f414dac1783183df40119" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage3.png"/>
        </fig>
        <fig id="figure-e8b9c74d530b4b6d966743536379ea8e" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 3 </label>
          <caption id="caption-1dd78be1e384428fae2dd85ad260b418">
            <title id="title-203d2258aed74896862a333004f6bea9"/>
          </caption>
          <graphic id="graphic-f4f160e8543a431ea6173d73d8e7d6eb" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage4.png"/>
        </fig>
        <fig id="figure-51e21a33951a4d0d8468c0f19ad19f3c" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 4 </label>
          <caption id="caption-26774f1588634ed6bbb28486935e3d81">
            <title id="title-404c2eb4666049c5b1a2357f3d9d9ff8"/>
          </caption>
          <graphic id="graphic-cf06b7d5acb44f6bac785e4fd0a72f2a" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage5.png"/>
        </fig>
      </sec>
      <sec>
        <title id="t-fc003c72d394">3.2 <bold id="strong-c738b8ab8e254128a07888e6b6cb87b1">Lymphocytes</bold></title>
        <p id="paragraph-72d9c67ac8134856a71b8ad4abb94ad6">Lymphocytes show large granular forms, reactive changes and plasmacytoid changes.</p>
        <fig id="figure-a442950562da45f488a2678d06462766" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 5 </label>
          <caption id="caption-f8e6c9f23ed24c45b61aeb1f866d2800">
            <title id="title-b4231b508cdd446b923155ff0b83e93d"/>
          </caption>
          <graphic id="graphic-1c616477c92e411180be6163486d53e3" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage6.png"/>
        </fig>
        <fig id="figure-181fa782d28f4c459170127ff2c79532" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 6 </label>
          <caption id="caption-e773bc0a057c48b8ba8485745cff9403">
            <title id="title-6f730d790541450f9200c7d4356389f7"/>
          </caption>
          <graphic id="graphic-e679626a924e4d0494443afa8c3dfeec" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage7.png"/>
        </fig>
        <fig id="figure-fb40a57400624f868d22e035b8a7395c" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 7 </label>
          <caption id="caption-d848424b75024b0dab1d59c94027c0f8">
            <title id="title-a7a50a9d4c6640d78673040e09f585cc"/>
          </caption>
          <graphic id="graphic-0afbbc80651c47febac8882346c2ddc1" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage8.png"/>
        </fig>
      </sec>
      <sec>
        <title id="t-2fa3399aa97f">3.3 <bold id="strong-a4238ef4024440aaa1ab4a0cce71a73c">Monocytes</bold></title>
        <p id="paragraph-b2d6178f1af34f539d5f3503d4ee996d">Monocytes showed cytoplasmic vacuoles and abnormal nuclear forms.</p>
        <fig id="figure-4caace6e19aa4e0cab6bcfe92b46fb5b" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 8 </label>
          <caption id="caption-ebfa4463b50347b191e658116e357358">
            <title id="title-96fa6594578943e29d1db21673e9c406"/>
          </caption>
          <graphic id="graphic-98f73a72269e4bd5ace2a9caed190024" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage9.png"/>
        </fig>
      </sec>
      <sec>
        <title id="t-bcc0288cf98c">3.4 <bold id="strong-8682086ba90b4adbab9d2d422c1599b2">Platelets</bold></title>
        <p id="paragraph-f05dd3a433294e6183d52804a78232ed">Majority of patients showed normal platelet counts and morphology. However, a few cases showed giant platelets, macroplatelets and large platelet clumps.</p>
        <fig id="figure-110b973df0794a2b931456f53263f979" orientation="portrait" fig-type="graphic" position="anchor">
          <label>Figure 9 </label>
          <caption id="caption-0ddde6b378414c5fa4154ced6e6a486b">
            <title id="title-c175b6d1192343a0890d4f4fc852ac7a"/>
          </caption>
          <graphic id="graphic-16750e25dd9441f285ed67c4f62a974b" xlink:href="https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/483735a4-7188-4745-b7fe-0119c1838c9fimage10.png"/>
        </fig>
      </sec>
    </sec>
    <sec>
      <title id="title-d074d948ac024863a1bbbef2fcaf919a">4 Discussion</title>
      <p id="paragraph-585312ce7a5e48dbb2054968f189a507">Covid-19 was initially found in China for the first time in 2019 which was later declared by the World Health Organization as a pandemic. <xref rid="R279374233846717" ref-type="bibr">1</xref>, <xref rid="R279374233846725" ref-type="bibr">3</xref>, <xref rid="R279374233846729" ref-type="bibr">9</xref> This virus is a single stranded ribonucleic acid virus. The pathogenesis of this disease is still being constructed every day. <xref rid="R279374233846716" ref-type="bibr">10</xref>, <xref rid="R279374233846722" ref-type="bibr">11</xref> So far, the research and literature available shows that the main mechanism by which the virus is infecting the host cell is by adhering its surface glycoprotein S with Angiotensin Converting enzyme 2 on epithelial cells and endothelial cells of the host. <xref rid="R279374233846721" ref-type="bibr">2</xref>, <xref rid="R279374233846726" ref-type="bibr">12</xref>, <xref rid="R279374233846723" ref-type="bibr">13</xref> Cell injury and destruction are seen as consequences once the virus enters the host cell, which in turn stimulate innate and adaptive immune system. <xref rid="R279374233846717" ref-type="bibr">1</xref>, <xref rid="R279374233846727" ref-type="bibr">14</xref>, <xref rid="R279374233846728" ref-type="bibr">15</xref></p>
      <p id="paragraph-57b331183e8a484c8b2c9f9e0bab29e4">Our study identified various morphological forms of all 3 cell lines in peripheral blood. Among 89 Covid – 19 patients, 66.2% showed normocytic normochromic blood picture, 22% showed normocytic normochromic anemia, very few cases showed microcytic hypochromic cells. All the patients showed normal platelets. However, 14.6% patients showed macro and 24.7% giant platelets. The abnormal forms in WBC’s include band forms, toxic granules, hypersegmented neutrophils, monolobulated nucleus, ring forms and foetal forms. Reactive lymphocytes, plasmacytoid cells were seen along with normal lymphocytes. Similar morphological forms are also reported in other studies. But very few authors have completely described the morphological forms in the peripheral smear.</p>
      <p id="paragraph-79ad7f79140b49efb39ae8262bf5d2b6">A study done by Singh A et al showed the various morphological forms of neutrophils such as fetal shaped cell, c shaped cell, ring forms. <xref id="xref-f00e2813d3ad4d2ab13793573b8c48de" rid="R279374233846724" ref-type="bibr">7</xref> Singh S et al also stressed about the giant and macroplatelets, shift to left of neutrophils and band forms in a study. <xref id="xref-8c33b81ae5404c3da1baa4957644a61a" rid="R279374233846723" ref-type="bibr">13</xref> Another study done by Kaur G et al reported large granular lymphocytes, plasmacytoid lymphocytes and various morphological forms of neutrophils among COVID -19 infected patients. <xref id="xref-bb3d69170d954d0189272dc7d918a758" rid="R279374233846729" ref-type="bibr">9</xref></p>
    </sec>
    <sec>
      <title id="title-9116475089614204b5f0cc319e057e38">5 Conclusion</title>
      <p id="paragraph-e011a1661eb74d46a7124bbeeff1a0dc">Our study identifies and describes significant morphologic changes in the peripheral blood cells of COVID 19 patients.<sup id="superscript-879d7d5265d14f788855adc411685079"> </sup>An understanding of these morphologic changes in addition to established hematologic parameters can aid in the diagnosis of COVID-19 and peripheral smear review may help with management decisions in COVID-19 patients. Follow-up peripheral blood smears can be used to assess the resolution of the infection.</p>
    </sec>
  </body>
  <back>
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