Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.
Identifieur interne : 000299 ( Main/Corpus ); précédent : 000298; suivant : 000300Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.
Auteurs : Zhihong Zuo ; Ting Wu ; Liangyu Pan ; Chenzhe Zuo ; Yingchuo Hu ; Xuan Luo ; Liping Jiang ; Zanxian Xia ; Xiaojuan Xiao ; Jing Liu ; Mao Ye ; Meichun DengSource :
- Frontiers in pharmacology [ 1663-9812 ] ; 2020.
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway. Current treatments could be divided into two major part: anti-viral agents and host system modulatory agents. On one hand, anti-viral agents focus on virus infection process. Umifenovir blocks virus recognizing host and entry. Remdesivir inhibits virus replication. Chloroquine and hydroxychloroquine involve preventing the whole infection process, including virus transcription and release. On the other hand, host system modulatory agents are associated with regulating the imbalanced inflammatory reaction and biased immune system. Corticosteroid is believed to be commonly used for repressing hyper-inflammation, which is one of the major pathologic mechanisms of COVID-19. Convalescent plasma and neutralizing antibodies provide essential elements for host immune system and create passive immunization. Thrombotic events are at high incidence in COVID-19 patients, thus anti-platelet and anti-coagulation are crucial, as well. Here, we summarized these current or reproposed agents to better understand the mechanisms of agents and give an update of present research situation.
DOI: 10.3389/fphar.2020.583914
PubMed: 33643033
PubMed Central: PMC7908061
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.</title><author><name sortKey="Zuo, Zhihong" sort="Zuo, Zhihong" uniqKey="Zuo Z" first="Zhihong" last="Zuo">Zhihong Zuo</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Ting" sort="Wu, Ting" uniqKey="Wu T" first="Ting" last="Wu">Ting Wu</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Pan, Liangyu" sort="Pan, Liangyu" uniqKey="Pan L" first="Liangyu" last="Pan">Liangyu Pan</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zuo, Chenzhe" sort="Zuo, Chenzhe" uniqKey="Zuo C" first="Chenzhe" last="Zuo">Chenzhe Zuo</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Hu, Yingchuo" sort="Hu, Yingchuo" uniqKey="Hu Y" first="Yingchuo" last="Hu">Yingchuo Hu</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Luo, Xuan" sort="Luo, Xuan" uniqKey="Luo X" first="Xuan" last="Luo">Xuan Luo</name><affiliation><nlm:affiliation>Hunan Yuanpin Cell Biotechnology Co., Ltd., Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Jiang, Liping" sort="Jiang, Liping" uniqKey="Jiang L" first="Liping" last="Jiang">Liping Jiang</name><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xia, Zanxian" sort="Xia, Zanxian" uniqKey="Xia Z" first="Zanxian" last="Xia">Zanxian Xia</name><affiliation><nlm:affiliation>Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xiao, Xiaojuan" sort="Xiao, Xiaojuan" uniqKey="Xiao X" first="Xiaojuan" last="Xiao">Xiaojuan Xiao</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ye, Mao" sort="Ye, Mao" uniqKey="Ye M" first="Mao" last="Ye">Mao Ye</name><affiliation><nlm:affiliation>Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Deng, Meichun" sort="Deng, Meichun" uniqKey="Deng M" first="Meichun" last="Deng">Meichun Deng</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33643033</idno><idno type="pmid">33643033</idno><idno type="doi">10.3389/fphar.2020.583914</idno><idno type="pmc">PMC7908061</idno><idno type="wicri:Area/Main/Corpus">000299</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000299</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.</title><author><name sortKey="Zuo, Zhihong" sort="Zuo, Zhihong" uniqKey="Zuo Z" first="Zhihong" last="Zuo">Zhihong Zuo</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Ting" sort="Wu, Ting" uniqKey="Wu T" first="Ting" last="Wu">Ting Wu</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Pan, Liangyu" sort="Pan, Liangyu" uniqKey="Pan L" first="Liangyu" last="Pan">Liangyu Pan</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Zuo, Chenzhe" sort="Zuo, Chenzhe" uniqKey="Zuo C" first="Chenzhe" last="Zuo">Chenzhe Zuo</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Hu, Yingchuo" sort="Hu, Yingchuo" uniqKey="Hu Y" first="Yingchuo" last="Hu">Yingchuo Hu</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Luo, Xuan" sort="Luo, Xuan" uniqKey="Luo X" first="Xuan" last="Luo">Xuan Luo</name><affiliation><nlm:affiliation>Hunan Yuanpin Cell Biotechnology Co., Ltd., Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Jiang, Liping" sort="Jiang, Liping" uniqKey="Jiang L" first="Liping" last="Jiang">Liping Jiang</name><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xia, Zanxian" sort="Xia, Zanxian" uniqKey="Xia Z" first="Zanxian" last="Xia">Zanxian Xia</name><affiliation><nlm:affiliation>Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xiao, Xiaojuan" sort="Xiao, Xiaojuan" uniqKey="Xiao X" first="Xiaojuan" last="Xiao">Xiaojuan Xiao</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ye, Mao" sort="Ye, Mao" uniqKey="Ye M" first="Mao" last="Ye">Mao Ye</name><affiliation><nlm:affiliation>Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China.</nlm:affiliation></affiliation></author><author><name sortKey="Deng, Meichun" sort="Deng, Meichun" uniqKey="Deng M" first="Meichun" last="Deng">Meichun Deng</name><affiliation><nlm:affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Frontiers in pharmacology</title><idno type="ISSN">1663-9812</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway. Current treatments could be divided into two major part: anti-viral agents and host system modulatory agents. On one hand, anti-viral agents focus on virus infection process. Umifenovir blocks virus recognizing host and entry. Remdesivir inhibits virus replication. Chloroquine and hydroxychloroquine involve preventing the whole infection process, including virus transcription and release. On the other hand, host system modulatory agents are associated with regulating the imbalanced inflammatory reaction and biased immune system. Corticosteroid is believed to be commonly used for repressing hyper-inflammation, which is one of the major pathologic mechanisms of COVID-19. Convalescent plasma and neutralizing antibodies provide essential elements for host immune system and create passive immunization. Thrombotic events are at high incidence in COVID-19 patients, thus anti-platelet and anti-coagulation are crucial, as well. Here, we summarized these current or reproposed agents to better understand the mechanisms of agents and give an update of present research situation.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33643033</PMID><DateRevised><Year>2021</Year><Month>03</Month><Day>03</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1663-9812</ISSN><JournalIssue CitedMedium="Print"><Volume>11</Volume><PubDate><Year>2020</Year></PubDate></JournalIssue><Title>Frontiers in pharmacology</Title><ISOAbbreviation>Front Pharmacol</ISOAbbreviation></Journal><ArticleTitle>Modalities and Mechanisms of Treatment for Coronavirus Disease 2019.</ArticleTitle><Pagination><MedlinePgn>583914</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fphar.2020.583914</ELocationID><Abstract><AbstractText>Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly throughout the world. Although COVID-19 has a relatively low case severity rate compared to SARS and Middle East Respiratory syndrome it is a major public concern because of its rapid spread and devastating impact on the global economy. Scientists and clinicians are urgently trying to identify drugs to combat the virus with hundreds of clinical trials underway. Current treatments could be divided into two major part: anti-viral agents and host system modulatory agents. On one hand, anti-viral agents focus on virus infection process. Umifenovir blocks virus recognizing host and entry. Remdesivir inhibits virus replication. Chloroquine and hydroxychloroquine involve preventing the whole infection process, including virus transcription and release. On the other hand, host system modulatory agents are associated with regulating the imbalanced inflammatory reaction and biased immune system. Corticosteroid is believed to be commonly used for repressing hyper-inflammation, which is one of the major pathologic mechanisms of COVID-19. Convalescent plasma and neutralizing antibodies provide essential elements for host immune system and create passive immunization. Thrombotic events are at high incidence in COVID-19 patients, thus anti-platelet and anti-coagulation are crucial, as well. Here, we summarized these current or reproposed agents to better understand the mechanisms of agents and give an update of present research situation.</AbstractText><CopyrightInformation>Copyright © 2021 Zuo, Wu, Pan, Zuo, Hu, Luo, Jiang, Xia, Xiao, Liu, Ye and Deng.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zuo</LastName><ForeName>Zhihong</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Ting</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Liangyu</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zuo</LastName><ForeName>Chenzhe</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Yingchuo</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Luo</LastName><ForeName>Xuan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Hunan Yuanpin Cell Biotechnology Co., Ltd., Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Liping</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xia</LastName><ForeName>Zanxian</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Cell Biology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xiao</LastName><ForeName>Xiaojuan</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ye</LastName><ForeName>Mao</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deng</LastName><ForeName>Meichun</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Biology and Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Xiangya School of Medicine, Central South University, Changsha, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Hunan Key Laboratory of Animal Models for Human Diseases, Hunan Key Laboratory of Medical Genetics and Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>02</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Pharmacol</MedlineTA><NlmUniqueID>101548923</NlmUniqueID><ISSNLinking>1663-9812</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword><Keyword MajorTopicYN="N">mechanisms</Keyword><Keyword MajorTopicYN="N">therapeutic agents</Keyword><Keyword MajorTopicYN="N">treatment</Keyword></KeywordList><CoiStatement>Author XL was employed by Hunan Yuanpin Cell Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>09</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>12</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>3</Month><Day>1</Day><Hour>5</Hour><Minute>35</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>3</Month><Day>2</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>3</Month><Day>2</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33643033</ArticleId><ArticleId 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