Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial.
Identifieur interne : 000A18 ( Main/Corpus ); précédent : 000A17; suivant : 000A19Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial.
Auteurs : Radha Rajasingham ; Ananta S. Bangdiwala ; Melanie R. Nicol ; Caleb P. Skipper ; Katelyn A. Pastick ; Margaret L. Axelrod ; Matthew F. Pullen ; Alanna A. Nascene ; Darlisha A. Williams ; Nicole W. Engen ; Elizabeth C. Okafor ; Brian I. Rini ; Ingrid A. Mayer ; Emily G. Mcdonald ; Todd C. Lee ; Peter Li ; Lauren J. Mackenzie ; Justin M. Balko ; Stephen J. Dunlop ; Katherine H. Hullsiek ; David R. Boulware ; Sarah M. LofgrenSource :
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [ 1537-6591 ] ; 2020.
Abstract
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.
METHODS
We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations.
RESULTS
We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18), and for twice-weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19-compatible illness (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08).
CONCLUSIONS
Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.
DOI: 10.1093/cid/ciaa1571
PubMed: 33068425
PubMed Central: PMC7665393
Links to Exploration step
pubmed:33068425Le document en format XML
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<author><name sortKey="Rini, Brian I" sort="Rini, Brian I" uniqKey="Rini B" first="Brian I" last="Rini">Brian I. Rini</name>
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<author><name sortKey="Mayer, Ingrid A" sort="Mayer, Ingrid A" uniqKey="Mayer I" first="Ingrid A" last="Mayer">Ingrid A. Mayer</name>
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<author><name sortKey="Lee, Todd C" sort="Lee, Todd C" uniqKey="Lee T" first="Todd C" last="Lee">Todd C. Lee</name>
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<author><name sortKey="Li, Peter" sort="Li, Peter" uniqKey="Li P" first="Peter" last="Li">Peter Li</name>
<affiliation><nlm:affiliation>Oregon Health & Science University, Portland, OR.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Mackenzie, Lauren J" sort="Mackenzie, Lauren J" uniqKey="Mackenzie L" first="Lauren J" last="Mackenzie">Lauren J. Mackenzie</name>
<affiliation><nlm:affiliation>Section of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba.</nlm:affiliation>
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<author><name sortKey="Balko, Justin M" sort="Balko, Justin M" uniqKey="Balko J" first="Justin M" last="Balko">Justin M. Balko</name>
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<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
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<affiliation><nlm:affiliation>Hennepin Healthcare, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Hullsiek, Katherine H" sort="Hullsiek, Katherine H" uniqKey="Hullsiek K" first="Katherine H" last="Hullsiek">Katherine H. Hullsiek</name>
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<author><name sortKey="Boulware, David R" sort="Boulware, David R" uniqKey="Boulware D" first="David R" last="Boulware">David R. Boulware</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial.</title>
<author><name sortKey="Rajasingham, Radha" sort="Rajasingham, Radha" uniqKey="Rajasingham R" first="Radha" last="Rajasingham">Radha Rajasingham</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
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<author><name sortKey="Bangdiwala, Ananta S" sort="Bangdiwala, Ananta S" uniqKey="Bangdiwala A" first="Ananta S" last="Bangdiwala">Ananta S. Bangdiwala</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
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<author><name sortKey="Nicol, Melanie R" sort="Nicol, Melanie R" uniqKey="Nicol M" first="Melanie R" last="Nicol">Melanie R. Nicol</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Skipper, Caleb P" sort="Skipper, Caleb P" uniqKey="Skipper C" first="Caleb P" last="Skipper">Caleb P. Skipper</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Pastick, Katelyn A" sort="Pastick, Katelyn A" uniqKey="Pastick K" first="Katelyn A" last="Pastick">Katelyn A. Pastick</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Axelrod, Margaret L" sort="Axelrod, Margaret L" uniqKey="Axelrod M" first="Margaret L" last="Axelrod">Margaret L. Axelrod</name>
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</affiliation>
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<author><name sortKey="Pullen, Matthew F" sort="Pullen, Matthew F" uniqKey="Pullen M" first="Matthew F" last="Pullen">Matthew F. Pullen</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Nascene, Alanna A" sort="Nascene, Alanna A" uniqKey="Nascene A" first="Alanna A" last="Nascene">Alanna A. Nascene</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Williams, Darlisha A" sort="Williams, Darlisha A" uniqKey="Williams D" first="Darlisha A" last="Williams">Darlisha A. Williams</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Engen, Nicole W" sort="Engen, Nicole W" uniqKey="Engen N" first="Nicole W" last="Engen">Nicole W. Engen</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Okafor, Elizabeth C" sort="Okafor, Elizabeth C" uniqKey="Okafor E" first="Elizabeth C" last="Okafor">Elizabeth C. Okafor</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Rini, Brian I" sort="Rini, Brian I" uniqKey="Rini B" first="Brian I" last="Rini">Brian I. Rini</name>
<affiliation><nlm:affiliation>Vanderbilt University Medical Center, Nashville, Tennessee.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mayer, Ingrid A" sort="Mayer, Ingrid A" uniqKey="Mayer I" first="Ingrid A" last="Mayer">Ingrid A. Mayer</name>
<affiliation><nlm:affiliation>Vanderbilt University Medical Center, Nashville, Tennessee.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mcdonald, Emily G" sort="Mcdonald, Emily G" uniqKey="Mcdonald E" first="Emily G" last="Mcdonald">Emily G. Mcdonald</name>
<affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre and the Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lee, Todd C" sort="Lee, Todd C" uniqKey="Lee T" first="Todd C" last="Lee">Todd C. Lee</name>
<affiliation><nlm:affiliation>Research Institute of the McGill University Health Centre and the Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Li, Peter" sort="Li, Peter" uniqKey="Li P" first="Peter" last="Li">Peter Li</name>
<affiliation><nlm:affiliation>Oregon Health & Science University, Portland, OR.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Mackenzie, Lauren J" sort="Mackenzie, Lauren J" uniqKey="Mackenzie L" first="Lauren J" last="Mackenzie">Lauren J. Mackenzie</name>
<affiliation><nlm:affiliation>Section of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Balko, Justin M" sort="Balko, Justin M" uniqKey="Balko J" first="Justin M" last="Balko">Justin M. Balko</name>
<affiliation><nlm:affiliation>Vanderbilt University Medical Center, Nashville, Tennessee.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Dunlop, Stephen J" sort="Dunlop, Stephen J" uniqKey="Dunlop S" first="Stephen J" last="Dunlop">Stephen J. Dunlop</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
<affiliation><nlm:affiliation>Hennepin Healthcare, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Hullsiek, Katherine H" sort="Hullsiek, Katherine H" uniqKey="Hullsiek K" first="Katherine H" last="Hullsiek">Katherine H. Hullsiek</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Boulware, David R" sort="Boulware, David R" uniqKey="Boulware D" first="David R" last="Boulware">David R. Boulware</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Lofgren, Sarah M" sort="Lofgren, Sarah M" uniqKey="Lofgren S" first="Sarah M" last="Lofgren">Sarah M. Lofgren</name>
<affiliation><nlm:affiliation>University of Minnesota, Minneapolis, Minnesota.</nlm:affiliation>
</affiliation>
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<idno type="eISSN">1537-6591</idno>
<imprint><date when="2020" type="published">2020</date>
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<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b>
</p>
<p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<p>We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<p>We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18), and for twice-weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19-compatible illness (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08).</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b>
</p>
<p>Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.</p>
</div>
</front>
</TEI>
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<Month>Oct</Month>
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<Title>Clinical infectious diseases : an official publication of the Infectious Diseases Society of America</Title>
<ISOAbbreviation>Clin Infect Dis</ISOAbbreviation>
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<ArticleTitle>Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial.</ArticleTitle>
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<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, Covid-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine 400mg once weekly or twice weekly for 12 weeks. The primary endpoint was confirmed or probable Covid-19-compatible illness. We measured hydroxychloroquine whole blood concentrations.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">We enrolled 1483 healthcare workers, of which 79% reported performing aerosol-generating procedures. The incidence of Covid-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events per person-year with once-weekly and 0.28 events per person-year with twice-weekly hydroxychloroquine compared with 0.38 events per person-year with placebo. For once weekly hydroxychloroquine prophylaxis, the hazard ratio was 0.72 (95%CI 0.44 to 1.16; P=0.18), and for twice-weekly was 0.74 (95%CI 0.46 to 1.19; P=0.22) as compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82-120) with once-weekly and 200 ng/mL (IQR, 159-258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed Covid-19-compatible illness (154 ng/mL) versus participants without Covid-19 (133 ng/mL; P=0.08).</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed Covid-19 or Covid-19-compatible illness among healthcare workers.</AbstractText>
<CopyrightInformation>© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rajasingham</LastName>
<ForeName>Radha</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bangdiwala</LastName>
<ForeName>Ananta S</ForeName>
<Initials>AS</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nicol</LastName>
<ForeName>Melanie R</ForeName>
<Initials>MR</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Skipper</LastName>
<ForeName>Caleb P</ForeName>
<Initials>CP</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pastick</LastName>
<ForeName>Katelyn A</ForeName>
<Initials>KA</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Axelrod</LastName>
<ForeName>Margaret L</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pullen</LastName>
<ForeName>Matthew F</ForeName>
<Initials>MF</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nascene</LastName>
<ForeName>Alanna A</ForeName>
<Initials>AA</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Williams</LastName>
<ForeName>Darlisha A</ForeName>
<Initials>DA</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Engen</LastName>
<ForeName>Nicole W</ForeName>
<Initials>NW</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Okafor</LastName>
<ForeName>Elizabeth C</ForeName>
<Initials>EC</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Rini</LastName>
<ForeName>Brian I</ForeName>
<Initials>BI</Initials>
<AffiliationInfo><Affiliation>Vanderbilt University Medical Center, Nashville, Tennessee.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mayer</LastName>
<ForeName>Ingrid A</ForeName>
<Initials>IA</Initials>
<AffiliationInfo><Affiliation>Vanderbilt University Medical Center, Nashville, Tennessee.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>McDonald</LastName>
<ForeName>Emily G</ForeName>
<Initials>EG</Initials>
<AffiliationInfo><Affiliation>Research Institute of the McGill University Health Centre and the Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lee</LastName>
<ForeName>Todd C</ForeName>
<Initials>TC</Initials>
<AffiliationInfo><Affiliation>Research Institute of the McGill University Health Centre and the Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Peter</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Oregon Health & Science University, Portland, OR.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>MacKenzie</LastName>
<ForeName>Lauren J</ForeName>
<Initials>LJ</Initials>
<AffiliationInfo><Affiliation>Section of Infectious Diseases, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Balko</LastName>
<ForeName>Justin M</ForeName>
<Initials>JM</Initials>
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<Initials>SJ</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
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<AffiliationInfo><Affiliation>Hennepin Healthcare, Minneapolis, Minnesota.</Affiliation>
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<Initials>KH</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
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<Initials>DR</Initials>
<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
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<AffiliationInfo><Affiliation>University of Minnesota, Minneapolis, Minnesota.</Affiliation>
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<Country>United States</Country>
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<Country>United States</Country>
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<Country>United States</Country>
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<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>10</Month>
<Day>17</Day>
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<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Clin Infect Dis</MedlineTA>
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<ISSNLinking>1058-4838</ISSNLinking>
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<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList><CommentsCorrections RefType="UpdateOf"><RefSource>medRxiv. 2020 Sep 18;:</RefSource>
<PMID Version="1">32995820</PMID>
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<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Covid-19</Keyword>
<Keyword MajorTopicYN="N">healthcare workers</Keyword>
<Keyword MajorTopicYN="N">hydroxychloroquine</Keyword>
<Keyword MajorTopicYN="N">pre-exposure prophylaxis</Keyword>
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<Day>17</Day>
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<Minute>0</Minute>
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<Day>18</Day>
<Hour>6</Hour>
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<ArticleId IdType="doi">10.1093/cid/ciaa1571</ArticleId>
<ArticleId IdType="pmc">PMC7665393</ArticleId>
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