Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.
Identifieur interne : 001135 ( PubMed/Corpus ); précédent : 001134; suivant : 001136Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.
Auteurs : Chan-Ki Min ; Shinhye Cheon ; Na-Young Ha ; Kyung Mok Sohn ; Yuri Kim ; Abdimadiyeva Aigerim ; Hyun Mu Shin ; Ji-Yeob Choi ; Kyung-Soo Inn ; Jin-Hwan Kim ; Jae Young Moon ; Myung-Sik Choi ; Nam-Hyuk Cho ; Yeon-Sook KimSource :
- Scientific reports [ 2045-2322 ] ; 2016.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Coronavirus Infections (complications), Coronavirus Infections (immunology), Coronavirus Infections (mortality), Coronavirus Infections (virology), Cytokines (metabolism), Epidermal Growth Factor (metabolism), Female, Humans, Kinetics, Leukocytosis (etiology), Leukocytosis (mortality), Lymphopenia (etiology), Lymphopenia (mortality), Male, Middle Aged, Middle East Respiratory Syndrome Coronavirus (physiology), Pneumonia (etiology), Pneumonia (mortality), Severity of Illness Index, Thrombocytopenia (etiology), Thrombocytopenia (mortality), Viral Load, Virus Shedding.
- MESH :
- chemical , metabolism : Cytokines, Epidermal Growth Factor.
- complications : Coronavirus Infections.
- etiology : Leukocytosis, Lymphopenia, Pneumonia, Thrombocytopenia.
- immunology : Coronavirus Infections.
- mortality : Coronavirus Infections, Leukocytosis, Lymphopenia, Pneumonia, Thrombocytopenia.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- virology : Coronavirus Infections.
- Adult, Aged, Aged, 80 and over, Female, Humans, Kinetics, Male, Middle Aged, Severity of Illness Index, Viral Load, Virus Shedding.
Abstract
Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.
DOI: 10.1038/srep25359
PubMed: 27146253
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pubmed:27146253Le document en format XML
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Ha</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name><affiliation><nlm:affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Yuri" sort="Kim, Yuri" uniqKey="Kim Y" first="Yuri" last="Kim">Yuri Kim</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Aigerim, Abdimadiyeva" sort="Aigerim, Abdimadiyeva" uniqKey="Aigerim A" first="Abdimadiyeva" last="Aigerim">Abdimadiyeva Aigerim</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Choi, Ji Yeob" sort="Choi, Ji Yeob" uniqKey="Choi J" first="Ji-Yeob" last="Choi">Ji-Yeob Choi</name><affiliation><nlm:affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Inn, Kyung Soo" sort="Inn, Kyung Soo" uniqKey="Inn K" first="Kyung-Soo" last="Inn">Kyung-Soo Inn</name><affiliation><nlm:affiliation>Department of Pharmaceutical 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University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><affiliation><nlm:affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27146253</idno><idno type="pmid">27146253</idno><idno type="doi">10.1038/srep25359</idno><idno 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Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Ha, Na Young" sort="Ha, Na Young" uniqKey="Ha N" first="Na-Young" last="Ha">Na-Young Ha</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name><affiliation><nlm:affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Yuri" sort="Kim, Yuri" uniqKey="Kim Y" first="Yuri" last="Kim">Yuri Kim</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Aigerim, Abdimadiyeva" sort="Aigerim, Abdimadiyeva" uniqKey="Aigerim A" first="Abdimadiyeva" last="Aigerim">Abdimadiyeva Aigerim</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Choi, Ji Yeob" sort="Choi, Ji Yeob" uniqKey="Choi J" first="Ji-Yeob" last="Choi">Ji-Yeob Choi</name><affiliation><nlm:affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Inn, Kyung Soo" sort="Inn, Kyung Soo" uniqKey="Inn K" first="Kyung-Soo" last="Inn">Kyung-Soo Inn</name><affiliation><nlm:affiliation>Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Jin Hwan" sort="Kim, Jin Hwan" uniqKey="Kim J" first="Jin-Hwan" last="Kim">Jin-Hwan Kim</name><affiliation><nlm:affiliation>Department of Radiology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Moon, Jae Young" sort="Moon, Jae Young" uniqKey="Moon J" first="Jae Young" last="Moon">Jae Young Moon</name><affiliation><nlm:affiliation>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Choi, Myung Sik" sort="Choi, Myung Sik" uniqKey="Choi M" first="Myung-Sik" last="Choi">Myung-Sik Choi</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name><affiliation><nlm:affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name><affiliation><nlm:affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Coronavirus Infections (complications)</term><term>Coronavirus Infections (immunology)</term><term>Coronavirus Infections (mortality)</term><term>Coronavirus Infections (virology)</term><term>Cytokines (metabolism)</term><term>Epidermal Growth Factor (metabolism)</term><term>Female</term><term>Humans</term><term>Kinetics</term><term>Leukocytosis (etiology)</term><term>Leukocytosis (mortality)</term><term>Lymphopenia (etiology)</term><term>Lymphopenia (mortality)</term><term>Male</term><term>Middle Aged</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Pneumonia (etiology)</term><term>Pneumonia (mortality)</term><term>Severity of Illness Index</term><term>Thrombocytopenia (etiology)</term><term>Thrombocytopenia (mortality)</term><term>Viral Load</term><term>Virus Shedding</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Epidermal Growth Factor</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Leukocytosis</term><term>Lymphopenia</term><term>Pneumonia</term><term>Thrombocytopenia</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term><term>Leukocytosis</term><term>Lymphopenia</term><term>Pneumonia</term><term>Thrombocytopenia</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Female</term><term>Humans</term><term>Kinetics</term><term>Male</term><term>Middle Aged</term><term>Severity of Illness Index</term><term>Viral Load</term><term>Virus Shedding</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27146253</PMID><DateCompleted><Year>2018</Year><Month>01</Month><Day>30</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>6</Volume><PubDate><Year>2016</Year><Month>05</Month><Day>05</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.</ArticleTitle><Pagination><MedlinePgn>25359</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/srep25359</ELocationID><Abstract><AbstractText>Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Min</LastName><ForeName>Chan-Ki</ForeName><Initials>CK</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheon</LastName><ForeName>Shinhye</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ha</LastName><ForeName>Na-Young</ForeName><Initials>NY</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sohn</LastName><ForeName>Kyung Mok</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Yuri</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aigerim</LastName><ForeName>Abdimadiyeva</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Hyun Mu</ForeName><Initials>HM</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choi</LastName><ForeName>Ji-Yeob</ForeName><Initials>JY</Initials><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Inn</LastName><ForeName>Kyung-Soo</ForeName><Initials>KS</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Jin-Hwan</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Radiology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moon</LastName><ForeName>Jae Young</ForeName><Initials>JY</Initials><AffiliationInfo><Affiliation>Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choi</LastName><ForeName>Myung-Sik</ForeName><Initials>MS</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cho</LastName><ForeName>Nam-Hyuk</ForeName><Initials>NH</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Yeon-Sook</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>05</Month><Day>05</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>62229-50-9</RegistryNumber><NameOfSubstance UI="D004815">Epidermal Growth Factor</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004815" MajorTopicYN="N">Epidermal Growth Factor</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007700" MajorTopicYN="N">Kinetics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007964" MajorTopicYN="N">Leukocytosis</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008231" MajorTopicYN="N">Lymphopenia</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle 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