Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.
Identifieur interne : 000B96 ( Main/Corpus ); précédent : 000B95; suivant : 000B97Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.
Auteurs : Tzu-Han Yang ; Chian-Ying Chou ; Yi-Fan Yang ; Chian-Shiu Chien ; Aliaksandr A. Yarmishyn ; Tzu-Ying Yang ; Cheng-Hsuan Liu ; Kao-Jung Chang ; Yi-Ping Yang ; Yuh-Lih ChangSource :
- Journal of the Chinese Medical Association : JCMA [ 1728-7731 ] ; 2021.
English descriptors
- KwdEn :
- Azithromycin (administration & dosage), COVID-19 (drug therapy), COVID-19 (mortality), COVID-19 (virology), Electrocardiography (drug effects), Humans (MeSH), Hydroxychloroquine (administration & dosage), Hydroxychloroquine (pharmacology), Hydroxychloroquine (therapeutic use), Publication Bias (MeSH), Randomized Controlled Trials as Topic (MeSH), SARS-CoV-2 (MeSH).
- MESH :
- chemical , administration & dosage : Azithromycin, Hydroxychloroquine.
- drug effects : Electrocardiography.
- drug therapy : COVID-19.
- mortality : COVID-19.
- chemical , pharmacology : Hydroxychloroquine.
- chemical , therapeutic use : Hydroxychloroquine.
- virology : COVID-19.
- Humans, Publication Bias, Randomized Controlled Trials as Topic, SARS-CoV-2.
Abstract
BACKGROUND
Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies, and the relevant researches have shown controversial results.
METHODS
Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models.
RESULTS
Nine trials involving 4112 patients were included in present meta-analysis. It was seen that HCQ-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.63-3.36) patients; however, it also showed benefits associated with the viral clearance in patients (OR, 27.18; 95% CI, 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance, and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely infected COVID-19 patients (OR, 0.27; 95% CI, 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR, 0.27; 95% CI, 0.13-0.58) compared to ≤14 days follow-up period group that conversely showed an increased mortality rate (OR, 2.09; 95% CI, 1.41-3.10).
CONCLUSION
Our results indicated that HCQ-AZI combination treatment increased mortality rate in patients with COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale, and long follow-up period studies in patients with COVID-19 are needed.
DOI: 10.1097/JCMA.0000000000000425
PubMed: 32947506
Links to Exploration step
pubmed:32947506Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.</title><author><name sortKey="Yang, Tzu Han" sort="Yang, Tzu Han" uniqKey="Yang T" first="Tzu-Han" last="Yang">Tzu-Han Yang</name><affiliation><nlm:affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chou, Chian Ying" sort="Chou, Chian Ying" uniqKey="Chou C" first="Chian-Ying" last="Chou">Chian-Ying Chou</name><affiliation><nlm:affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Yi Fan" sort="Yang, Yi Fan" uniqKey="Yang Y" first="Yi-Fan" last="Yang">Yi-Fan Yang</name><affiliation><nlm:affiliation>Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chien, Chian Shiu" sort="Chien, Chian Shiu" uniqKey="Chien C" first="Chian-Shiu" last="Chien">Chian-Shiu Chien</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yarmishyn, Aliaksandr A" sort="Yarmishyn, Aliaksandr A" uniqKey="Yarmishyn A" first="Aliaksandr A" last="Yarmishyn">Aliaksandr A. Yarmishyn</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Tzu Ying" sort="Yang, Tzu Ying" uniqKey="Yang T" first="Tzu-Ying" last="Yang">Tzu-Ying Yang</name><affiliation><nlm:affiliation>Department of Dietetics and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Cheng Hsuan" sort="Liu, Cheng Hsuan" uniqKey="Liu C" first="Cheng-Hsuan" last="Liu">Cheng-Hsuan Liu</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, Kao Jung" sort="Chang, Kao Jung" uniqKey="Chang K" first="Kao-Jung" last="Chang">Kao-Jung Chang</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Yi Ping" sort="Yang, Yi Ping" uniqKey="Yang Y" first="Yi-Ping" last="Yang">Yi-Ping Yang</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, Yuh Lih" sort="Chang, Yuh Lih" uniqKey="Chang Y" first="Yuh-Lih" last="Chang">Yuh-Lih Chang</name><affiliation><nlm:affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:32947506</idno><idno type="pmid">32947506</idno><idno type="doi">10.1097/JCMA.0000000000000425</idno><idno type="wicri:Area/Main/Corpus">000B96</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000B96</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.</title><author><name sortKey="Yang, Tzu Han" sort="Yang, Tzu Han" uniqKey="Yang T" first="Tzu-Han" last="Yang">Tzu-Han Yang</name><affiliation><nlm:affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chou, Chian Ying" sort="Chou, Chian Ying" uniqKey="Chou C" first="Chian-Ying" last="Chou">Chian-Ying Chou</name><affiliation><nlm:affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Yi Fan" sort="Yang, Yi Fan" uniqKey="Yang Y" first="Yi-Fan" last="Yang">Yi-Fan Yang</name><affiliation><nlm:affiliation>Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chien, Chian Shiu" sort="Chien, Chian Shiu" uniqKey="Chien C" first="Chian-Shiu" last="Chien">Chian-Shiu Chien</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yarmishyn, Aliaksandr A" sort="Yarmishyn, Aliaksandr A" uniqKey="Yarmishyn A" first="Aliaksandr A" last="Yarmishyn">Aliaksandr A. Yarmishyn</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Tzu Ying" sort="Yang, Tzu Ying" uniqKey="Yang T" first="Tzu-Ying" last="Yang">Tzu-Ying Yang</name><affiliation><nlm:affiliation>Department of Dietetics and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Cheng Hsuan" sort="Liu, Cheng Hsuan" uniqKey="Liu C" first="Cheng-Hsuan" last="Liu">Cheng-Hsuan Liu</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, Kao Jung" sort="Chang, Kao Jung" uniqKey="Chang K" first="Kao-Jung" last="Chang">Kao-Jung Chang</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Yang, Yi Ping" sort="Yang, Yi Ping" uniqKey="Yang Y" first="Yi-Ping" last="Yang">Yi-Ping Yang</name><affiliation><nlm:affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author><author><name sortKey="Chang, Yuh Lih" sort="Chang, Yuh Lih" uniqKey="Chang Y" first="Yuh-Lih" last="Chang">Yuh-Lih Chang</name><affiliation><nlm:affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of the Chinese Medical Association : JCMA</title><idno type="eISSN">1728-7731</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Azithromycin (administration & dosage)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (mortality)</term><term>COVID-19 (virology)</term><term>Electrocardiography (drug effects)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (administration & dosage)</term><term>Hydroxychloroquine (pharmacology)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Publication Bias (MeSH)</term><term>Randomized Controlled Trials as Topic (MeSH)</term><term>SARS-CoV-2 (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Azithromycin</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Electrocardiography</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Publication Bias</term><term>Randomized Controlled Trials as Topic</term><term>SARS-CoV-2</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies, and the relevant researches have shown controversial results.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Nine trials involving 4112 patients were included in present meta-analysis. It was seen that HCQ-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.63-3.36) patients; however, it also showed benefits associated with the viral clearance in patients (OR, 27.18; 95% CI, 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance, and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely infected COVID-19 patients (OR, 0.27; 95% CI, 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR, 0.27; 95% CI, 0.13-0.58) compared to ≤14 days follow-up period group that conversely showed an increased mortality rate (OR, 2.09; 95% CI, 1.41-3.10).</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Our results indicated that HCQ-AZI combination treatment increased mortality rate in patients with COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale, and long follow-up period studies in patients with COVID-19 are needed.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32947506</PMID><DateCompleted><Year>2021</Year><Month>02</Month><Day>15</Day></DateCompleted><DateRevised><Year>2021</Year><Month>02</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1728-7731</ISSN><JournalIssue CitedMedium="Internet"><Volume>84</Volume><Issue>2</Issue><PubDate><Year>2021</Year><Month>02</Month><Day>01</Day></PubDate></JournalIssue><Title>Journal of the Chinese Medical Association : JCMA</Title><ISOAbbreviation>J Chin Med Assoc</ISOAbbreviation></Journal><ArticleTitle>Systematic review and meta-analysis of the effectiveness and safety of hydroxychloroquine in treating COVID-19 patients.</ArticleTitle><Pagination><MedlinePgn>233-241</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1097/JCMA.0000000000000425</ELocationID><Abstract><AbstractText Label="BACKGROUND">Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies, and the relevant researches have shown controversial results.</AbstractText><AbstractText Label="METHODS">Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models.</AbstractText><AbstractText Label="RESULTS">Nine trials involving 4112 patients were included in present meta-analysis. It was seen that HCQ-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.63-3.36) patients; however, it also showed benefits associated with the viral clearance in patients (OR, 27.18; 95% CI, 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance, and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely infected COVID-19 patients (OR, 0.27; 95% CI, 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR, 0.27; 95% CI, 0.13-0.58) compared to ≤14 days follow-up period group that conversely showed an increased mortality rate (OR, 2.09; 95% CI, 1.41-3.10).</AbstractText><AbstractText Label="CONCLUSION">Our results indicated that HCQ-AZI combination treatment increased mortality rate in patients with COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale, and long follow-up period studies in patients with COVID-19 are needed.</AbstractText><CopyrightInformation>Copyright © 2020, the Chinese Medical Association.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Tzu-Han</ForeName><Initials>TH</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chou</LastName><ForeName>Chian-Ying</ForeName><Initials>CY</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Yi-Fan</ForeName><Initials>YF</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chien</LastName><ForeName>Chian-Shiu</ForeName><Initials>CS</Initials><AffiliationInfo><Affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yarmishyn</LastName><ForeName>Aliaksandr A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Tzu-Ying</ForeName><Initials>TY</Initials><AffiliationInfo><Affiliation>Department of Dietetics and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Cheng-Hsuan</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Kao-Jung</ForeName><Initials>KJ</Initials><AffiliationInfo><Affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yang</LastName><ForeName>Yi-Ping</ForeName><Initials>YP</Initials><AffiliationInfo><Affiliation>Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Yuh-Lih</ForeName><Initials>YL</Initials><AffiliationInfo><Affiliation>Department of Pharmacy, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC.</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="D000078182">Systematic Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Chin Med Assoc</MedlineTA><NlmUniqueID>101174817</NlmUniqueID><ISSNLinking>1726-4901</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>83905-01-5</RegistryNumber><NameOfSubstance UI="D017963">Azithromycin</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Protocol" UI="C000705127">COVID-19 drug treatment</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D017963" MajorTopicYN="N">Azithromycin</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017594" MajorTopicYN="N">Publication Bias</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="Y">SARS-CoV-2</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>18</Day><Hour>20</Hour><Minute>25</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32947506</ArticleId><ArticleId IdType="pii">02118582-202102000-00019</ArticleId><ArticleId IdType="doi">10.1097/JCMA.0000000000000425</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Wu YC, Chen CS, Chan YJ. 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