Current status of potential therapeutic candidates for the COVID-19 crisis.
Identifieur interne : 001882 ( Main/Corpus ); précédent : 001881; suivant : 001883Current status of potential therapeutic candidates for the COVID-19 crisis.
Auteurs : Jiancheng Zhang ; Bing Xie ; Kenji HashimotoSource :
- Brain, behavior, and immunity [ 1090-2139 ] ; 2020.
English descriptors
- KwdEn :
- Adrenal Cortex Hormones (therapeutic use), Angiotensin-Converting Enzyme 2 (MeSH), Anti-Inflammatory Agents, Non-Steroidal (therapeutic use), Antibodies, Monoclonal, Humanized (therapeutic use), Anticoagulants (therapeutic use), Antimalarials (therapeutic use), Antiviral Agents (therapeutic use), Betacoronavirus (MeSH), Bevacizumab (therapeutic use), COVID-19 (MeSH), COVID-19 Vaccines (MeSH), Chloroquine (therapeutic use), Coronavirus Infections (drug therapy), Coronavirus Infections (prevention & control), Coronavirus Infections (therapy), Humans (MeSH), Hydroxychloroquine (therapeutic use), Immunization, Passive (MeSH), Immunoglobulins, Intravenous (therapeutic use), Immunologic Factors (therapeutic use), Interferons (therapeutic use), Janus Kinase Inhibitors (therapeutic use), Killer Cells, Natural (MeSH), Medicine, Chinese Traditional (MeSH), Mesenchymal Stem Cell Transplantation (MeSH), Nitric Oxide (therapeutic use), Pandemics (MeSH), Peptidyl-Dipeptidase A (MeSH), Pneumonia, Viral (therapy), SARS-CoV-2 (MeSH), Spike Glycoprotein, Coronavirus (MeSH), Trace Elements (therapeutic use), Viral Vaccines (therapeutic use), Vitamins (therapeutic use), Zinc (therapeutic use).
- MESH :
- chemical , therapeutic use : Adrenal Cortex Hormones, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Humanized, Anticoagulants, Antimalarials, Antiviral Agents, Bevacizumab, Chloroquine, Hydroxychloroquine, Immunoglobulins, Intravenous, Immunologic Factors, Interferons, Janus Kinase Inhibitors, Nitric Oxide, Trace Elements, Viral Vaccines, Vitamins, Zinc.
- chemical : Angiotensin-Converting Enzyme 2, COVID-19 Vaccines, Peptidyl-Dipeptidase A, Spike Glycoprotein, Coronavirus.
- drug therapy : Coronavirus Infections.
- prevention & control : Coronavirus Infections.
- therapy : Coronavirus Infections, Pneumonia, Viral.
- Betacoronavirus, COVID-19, Humans, Immunization, Passive, Killer Cells, Natural, Medicine, Chinese Traditional, Mesenchymal Stem Cell Transplantation, Pandemics, SARS-CoV-2.
Abstract
As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.
DOI: 10.1016/j.bbi.2020.04.046
PubMed: 32334062
PubMed Central: PMC7175848
Links to Exploration step
pubmed:32334062Le document en format XML
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Electronic address: hashimoto@faculty.chiba-u.jp.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32334062</idno><idno type="pmid">32334062</idno><idno type="doi">10.1016/j.bbi.2020.04.046</idno><idno type="pmc">PMC7175848</idno><idno type="wicri:Area/Main/Corpus">001882</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001882</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Current status of potential therapeutic candidates for the COVID-19 crisis.</title><author><name sortKey="Zhang, Jiancheng" sort="Zhang, Jiancheng" uniqKey="Zhang J" first="Jiancheng" last="Zhang">Jiancheng Zhang</name><affiliation><nlm:affiliation>Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xie, Bing" sort="Xie, Bing" uniqKey="Xie B" first="Bing" last="Xie">Bing Xie</name><affiliation><nlm:affiliation>Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.</nlm:affiliation></affiliation></author><author><name sortKey="Hashimoto, Kenji" sort="Hashimoto, Kenji" uniqKey="Hashimoto K" first="Kenji" last="Hashimoto">Kenji Hashimoto</name><affiliation><nlm:affiliation>Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Brain, behavior, and immunity</title><idno type="eISSN">1090-2139</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adrenal Cortex Hormones (therapeutic use)</term><term>Angiotensin-Converting Enzyme 2 (MeSH)</term><term>Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)</term><term>Antibodies, Monoclonal, Humanized (therapeutic use)</term><term>Anticoagulants (therapeutic use)</term><term>Antimalarials (therapeutic use)</term><term>Antiviral Agents (therapeutic use)</term><term>Betacoronavirus (MeSH)</term><term>Bevacizumab (therapeutic use)</term><term>COVID-19 (MeSH)</term><term>COVID-19 Vaccines (MeSH)</term><term>Chloroquine (therapeutic use)</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (prevention & control)</term><term>Coronavirus Infections (therapy)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Immunization, Passive (MeSH)</term><term>Immunoglobulins, Intravenous (therapeutic use)</term><term>Immunologic Factors (therapeutic use)</term><term>Interferons (therapeutic use)</term><term>Janus Kinase Inhibitors (therapeutic use)</term><term>Killer Cells, Natural (MeSH)</term><term>Medicine, Chinese Traditional (MeSH)</term><term>Mesenchymal Stem Cell Transplantation (MeSH)</term><term>Nitric Oxide (therapeutic use)</term><term>Pandemics (MeSH)</term><term>Peptidyl-Dipeptidase A (MeSH)</term><term>Pneumonia, Viral (therapy)</term><term>SARS-CoV-2 (MeSH)</term><term>Spike Glycoprotein, Coronavirus (MeSH)</term><term>Trace Elements (therapeutic use)</term><term>Viral Vaccines (therapeutic use)</term><term>Vitamins (therapeutic use)</term><term>Zinc (therapeutic use)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adrenal Cortex Hormones</term><term>Anti-Inflammatory Agents, Non-Steroidal</term><term>Antibodies, Monoclonal, Humanized</term><term>Anticoagulants</term><term>Antimalarials</term><term>Antiviral Agents</term><term>Bevacizumab</term><term>Chloroquine</term><term>Hydroxychloroquine</term><term>Immunoglobulins, Intravenous</term><term>Immunologic Factors</term><term>Interferons</term><term>Janus Kinase Inhibitors</term><term>Nitric Oxide</term><term>Trace Elements</term><term>Viral Vaccines</term><term>Vitamins</term><term>Zinc</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Angiotensin-Converting Enzyme 2</term><term>COVID-19 Vaccines</term><term>Peptidyl-Dipeptidase A</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Betacoronavirus</term><term>COVID-19</term><term>Humans</term><term>Immunization, Passive</term><term>Killer Cells, Natural</term><term>Medicine, Chinese Traditional</term><term>Mesenchymal Stem Cell Transplantation</term><term>Pandemics</term><term>SARS-CoV-2</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32334062</PMID><DateCompleted><Year>2020</Year><Month>07</Month><Day>02</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1090-2139</ISSN><JournalIssue CitedMedium="Internet"><Volume>87</Volume><PubDate><Year>2020</Year><Month>07</Month></PubDate></JournalIssue><Title>Brain, behavior, and immunity</Title><ISOAbbreviation>Brain Behav Immun</ISOAbbreviation></Journal><ArticleTitle>Current status of potential therapeutic candidates for the COVID-19 crisis.</ArticleTitle><Pagination><MedlinePgn>59-73</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0889-1591(20)30589-4</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.bbi.2020.04.046</ELocationID><Abstract><AbstractText>As of April 15, 2020, the ongoing coronavirus disease 2019 (COVID-2019) pandemic has swept through 213 countries and infected more than 1,870,000 individuals, posing an unprecedented threat to international health and the economy. There is currently no specific treatment available for patients with COVID-19 infection. The lessons learned from past management of respiratory viral infections have provided insights into treating COVID-19. Numerous potential therapies, including supportive intervention, immunomodulatory agents, antiviral therapy, and convalescent plasma transfusion, have been tentatively applied in clinical settings. A number of these therapies have provided substantially curative benefits in treating patients with COVID-19 infection. Furthermore, intensive research and clinical trials are underway to assess the efficacy of existing drugs and identify potential therapeutic targets to develop new drugs for treating COVID-19. Herein, we summarize the current potential therapeutic approaches for diseases related to COVID-19 infection and introduce their mechanisms of action, safety, and effectiveness.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Jiancheng</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xie</LastName><ForeName>Bing</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hashimoto</LastName><ForeName>Kenji</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan. Electronic address: hashimoto@faculty.chiba-u.jp.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>04</Month><Day>22</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Brain Behav Immun</MedlineTA><NlmUniqueID>8800478</NlmUniqueID><ISSNLinking>0889-1591</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000305">Adrenal Cortex Hormones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000894">Anti-Inflammatory Agents, Non-Steroidal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>9008-11-1</RegistryNumber><NameOfSubstance UI="D007372">Interferons</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.15.1</RegistryNumber><NameOfSubstance UI="D007703">Peptidyl-Dipeptidase A</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.17.23</RegistryNumber><NameOfSubstance UI="C000705307">ACE2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.17.23</RegistryNumber><NameOfSubstance UI="D000085962">Angiotensin-Converting Enzyme 2</NameOfSubstance></Chemical><Chemical><RegistryNumber>I031V2H011</RegistryNumber><NameOfSubstance UI="C502936">tocilizumab</NameOfSubstance></Chemical><Chemical><RegistryNumber>J41CSQ7QDS</RegistryNumber><NameOfSubstance UI="D015032">Zinc</NameOfSubstance></Chemical><Chemical><RegistryNumber>NU90V55F8I</RegistryNumber><NameOfSubstance UI="C000592401">sarilumab</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName><SupplMeshName Type="Protocol" UI="C000705128">COVID-19 serotherapy</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000305" MajorTopicYN="N">Adrenal Cortex Hormones</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000085962" MajorTopicYN="N">Angiotensin-Converting Enzyme 2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000894" MajorTopicYN="N">Anti-Inflammatory Agents, Non-Steroidal</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D061067" MajorTopicYN="N">Antibodies, Monoclonal, Humanized</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000925" MajorTopicYN="N">Anticoagulants</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000962" MajorTopicYN="N">Antimalarials</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000068258" MajorTopicYN="N">Bevacizumab</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086663" MajorTopicYN="N">COVID-19 Vaccines</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000517" MajorTopicYN="N">prevention & control</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007116" MajorTopicYN="N">Immunization, Passive</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016756" MajorTopicYN="N">Immunoglobulins, Intravenous</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007155" MajorTopicYN="N">Immunologic Factors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007372" MajorTopicYN="N">Interferons</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000075242" MajorTopicYN="N">Janus Kinase Inhibitors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007694" MajorTopicYN="N">Killer Cells, Natural</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008516" MajorTopicYN="N">Medicine, Chinese Traditional</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045164" MajorTopicYN="N">Mesenchymal Stem Cell Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009569" MajorTopicYN="N">Nitric Oxide</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007703" MajorTopicYN="N">Peptidyl-Dipeptidase A</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014131" MajorTopicYN="N">Trace Elements</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014765" MajorTopicYN="N">Viral Vaccines</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014815" MajorTopicYN="N">Vitamins</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015032" MajorTopicYN="N">Zinc</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">ACE2 blocker</Keyword><Keyword MajorTopicYN="Y">Antimalaria</Keyword><Keyword MajorTopicYN="Y">Antiviral: Chinese traditional medicine</Keyword><Keyword MajorTopicYN="Y">COVID-19</Keyword><Keyword MajorTopicYN="Y">Immunoenhancer</Keyword><Keyword MajorTopicYN="Y">Monoclonal antibody</Keyword><Keyword MajorTopicYN="Y">Vaccine</Keyword></KeywordList><CoiStatement>Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>04</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>04</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>04</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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