Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study.
Identifieur interne : 000952 ( Main/Exploration ); précédent : 000951; suivant : 000953Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study.
Auteurs : Lars Christian Lund [Danemark] ; Kasper Bruun Kristensen [Danemark] ; Mette Reilev [Danemark] ; Steffen Christensen [Danemark] ; Reimar Wernich Thomsen [Danemark] ; Christian Fynbo Christiansen [Danemark] ; Henrik St Vring [Danemark] ; Nanna Borup Johansen [Danemark] ; Nikolai Constantin Brun [Danemark] ; Jesper Hallas [Danemark] ; Anton Potteg Rd [Danemark]Source :
- PLoS medicine [ 1549-1676 ] ; 2020.
Descripteurs français
- KwdFr :
- Adulte (MeSH), Adulte d'âge moyen (MeSH), Anti-inflammatoires non stéroïdiens (effets indésirables), Betacoronavirus (MeSH), Danemark (MeSH), Dialyse rénale (MeSH), Femelle (MeSH), Hospitalisation (MeSH), Humains (MeSH), Infections à coronavirus (mortalité), Infections à coronavirus (virologie), Mâle (MeSH), Odds ratio (MeSH), Ordonnances médicamenteuses (MeSH), Pandémies (MeSH), Pneumopathie virale (mortalité), Pneumopathie virale (virologie), Rein (MeSH), Sujet âgé (MeSH), Unités de soins intensifs (MeSH), Ventilation artificielle (MeSH), Études de cohortes (MeSH).
- MESH :
- effets indésirables : Anti-inflammatoires non stéroïdiens.
- mortalité : Infections à coronavirus, Pneumopathie virale.
- virologie : Infections à coronavirus, Pneumopathie virale.
- Adulte, Adulte d'âge moyen, Betacoronavirus, Danemark, Dialyse rénale, Femelle, Hospitalisation, Humains, Mâle, Odds ratio, Ordonnances médicamenteuses, Pandémies, Rein, Sujet âgé, Unités de soins intensifs, Ventilation artificielle, Études de cohortes.
- Wicri :
- geographic : Danemark.
English descriptors
- KwdEn :
- Adult (MeSH), Aged (MeSH), Anti-Inflammatory Agents, Non-Steroidal (adverse effects), Betacoronavirus (MeSH), Cohort Studies (MeSH), Coronavirus Infections (mortality), Coronavirus Infections (virology), Denmark (MeSH), Drug Prescriptions (MeSH), Female (MeSH), Hospitalization (MeSH), Humans (MeSH), Intensive Care Units (MeSH), Kidney (MeSH), Male (MeSH), Middle Aged (MeSH), Odds Ratio (MeSH), Pandemics (MeSH), Pneumonia, Viral (mortality), Pneumonia, Viral (virology), Renal Dialysis (MeSH), Respiration, Artificial (MeSH).
- MESH :
- chemical , adverse effects : Anti-Inflammatory Agents, Non-Steroidal.
- geographic : Denmark.
- mortality : Coronavirus Infections, Pneumonia, Viral.
- virology : Coronavirus Infections, Pneumonia, Viral.
- Adult, Aged, Betacoronavirus, Cohort Studies, Drug Prescriptions, Female, Hospitalization, Humans, Intensive Care Units, Kidney, Male, Middle Aged, Odds Ratio, Pandemics, Renal Dialysis, Respiration, Artificial.
Abstract
BACKGROUND
Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.
METHODS AND FINDINGS
We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI -3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI -3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI -3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI -2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD -0.2%, 95% CI -2.0% to 1.6%, p = 0.81). The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.
CONCLUSIONS
Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.
TRIAL REGISTRATION
The European Union electronic Register of Post-Authorisation Studies EUPAS34734.
DOI: 10.1371/journal.pmed.1003308
PubMed: 32898149
PubMed Central: PMC7478808
Affiliations:
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uniqKey="Lund L" first="Lars Christian" last="Lund">Lars Christian Lund</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense</wicri:regionArea><wicri:noRegion>Odense</wicri:noRegion></affiliation></author><author><name sortKey="Kristensen, Kasper Bruun" sort="Kristensen, Kasper Bruun" uniqKey="Kristensen K" first="Kasper Bruun" last="Kristensen">Kasper Bruun Kristensen</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern 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xml:lang="fr">Danemark</country><wicri:regionArea>Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Aarhus</wicri:regionArea><wicri:noRegion>Aarhus</wicri:noRegion></affiliation></author><author><name sortKey="Thomsen, Reimar Wernich" sort="Thomsen, Reimar Wernich" uniqKey="Thomsen R" first="Reimar Wernich" last="Thomsen">Reimar Wernich Thomsen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus</wicri:regionArea><wicri:noRegion>Aarhus</wicri:noRegion></affiliation></author><author><name sortKey="Christiansen, Christian Fynbo" sort="Christiansen, Christian Fynbo" uniqKey="Christiansen C" first="Christian Fynbo" last="Christiansen">Christian Fynbo Christiansen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus</wicri:regionArea><wicri:noRegion>Aarhus</wicri:noRegion></affiliation></author><author><name sortKey="St Vring, Henrik" sort="St Vring, Henrik" uniqKey="St Vring H" first="Henrik" last="St Vring">Henrik St Vring</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense</wicri:regionArea><wicri:noRegion>Odense</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Biostatistics, Department of Public Health, Aarhus University, Aarhus</wicri:regionArea><wicri:noRegion>Aarhus</wicri:noRegion></affiliation></author><author><name sortKey="Johansen, Nanna Borup" sort="Johansen, Nanna Borup" uniqKey="Johansen N" first="Nanna Borup" last="Johansen">Nanna Borup Johansen</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen</wicri:regionArea><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author><author><name sortKey="Brun, Nikolai Constantin" sort="Brun, Nikolai Constantin" uniqKey="Brun N" first="Nikolai Constantin" last="Brun">Nikolai Constantin Brun</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen</wicri:regionArea><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author><author><name sortKey="Hallas, Jesper" sort="Hallas, Jesper" uniqKey="Hallas J" first="Jesper" last="Hallas">Jesper Hallas</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense</wicri:regionArea><wicri:noRegion>Odense</wicri:noRegion></affiliation></author><author><name sortKey="Potteg Rd, Anton" sort="Potteg Rd, Anton" uniqKey="Potteg Rd A" first="Anton" last="Potteg Rd">Anton Potteg Rd</name><affiliation wicri:level="1"><nlm:affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense</wicri:regionArea><wicri:noRegion>Odense</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS medicine</title><idno type="eISSN">1549-1676</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term><term>Aged (MeSH)</term><term>Anti-Inflammatory Agents, Non-Steroidal (adverse effects)</term><term>Betacoronavirus (MeSH)</term><term>Cohort Studies (MeSH)</term><term>Coronavirus Infections (mortality)</term><term>Coronavirus Infections (virology)</term><term>Denmark (MeSH)</term><term>Drug Prescriptions (MeSH)</term><term>Female (MeSH)</term><term>Hospitalization (MeSH)</term><term>Humans (MeSH)</term><term>Intensive Care Units (MeSH)</term><term>Kidney (MeSH)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Odds Ratio (MeSH)</term><term>Pandemics (MeSH)</term><term>Pneumonia, Viral (mortality)</term><term>Pneumonia, Viral (virology)</term><term>Renal Dialysis (MeSH)</term><term>Respiration, Artificial (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term><term>Adulte d'âge moyen (MeSH)</term><term>Anti-inflammatoires non stéroïdiens (effets indésirables)</term><term>Betacoronavirus (MeSH)</term><term>Danemark (MeSH)</term><term>Dialyse rénale (MeSH)</term><term>Femelle (MeSH)</term><term>Hospitalisation (MeSH)</term><term>Humains (MeSH)</term><term>Infections à coronavirus (mortalité)</term><term>Infections à coronavirus (virologie)</term><term>Mâle (MeSH)</term><term>Odds ratio (MeSH)</term><term>Ordonnances médicamenteuses (MeSH)</term><term>Pandémies (MeSH)</term><term>Pneumopathie virale (mortalité)</term><term>Pneumopathie virale (virologie)</term><term>Rein (MeSH)</term><term>Sujet âgé (MeSH)</term><term>Unités de soins intensifs (MeSH)</term><term>Ventilation artificielle (MeSH)</term><term>Études de cohortes (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Anti-Inflammatory Agents, Non-Steroidal</term></keywords><keywords scheme="MESH" type="geographic" xml:lang="en"><term>Denmark</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Anti-inflammatoires non stéroïdiens</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term><term>Pneumopathie virale</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term><term>Pneumonia, Viral</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Betacoronavirus</term><term>Cohort Studies</term><term>Drug Prescriptions</term><term>Female</term><term>Hospitalization</term><term>Humans</term><term>Intensive Care Units</term><term>Kidney</term><term>Male</term><term>Middle Aged</term><term>Odds Ratio</term><term>Pandemics</term><term>Renal Dialysis</term><term>Respiration, Artificial</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Adulte d'âge moyen</term><term>Betacoronavirus</term><term>Danemark</term><term>Dialyse rénale</term><term>Femelle</term><term>Hospitalisation</term><term>Humains</term><term>Mâle</term><term>Odds ratio</term><term>Ordonnances médicamenteuses</term><term>Pandémies</term><term>Rein</term><term>Sujet âgé</term><term>Unités de soins intensifs</term><term>Ventilation artificielle</term><term>Études de cohortes</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Danemark</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS AND FINDINGS</b></p><p>We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI -3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI -3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI -3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI -2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD -0.2%, 95% CI -2.0% to 1.6%, p = 0.81). The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.</p></div><div type="abstract" xml:lang="en"><p><b>TRIAL REGISTRATION</b></p><p>The European Union electronic Register of Post-Authorisation Studies EUPAS34734.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32898149</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>10</Month><Day>01</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1549-1676</ISSN><JournalIssue CitedMedium="Internet"><Volume>17</Volume><Issue>9</Issue><PubDate><Year>2020</Year><Month>09</Month></PubDate></JournalIssue><Title>PLoS medicine</Title><ISOAbbreviation>PLoS Med</ISOAbbreviation></Journal><ArticleTitle>Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study.</ArticleTitle><Pagination><MedlinePgn>e1003308</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pmed.1003308</ELocationID><Abstract><AbstractText Label="BACKGROUND">Concerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been raised. We studied whether use of NSAIDs was associated with adverse outcomes and mortality during SARS-CoV-2 infection.</AbstractText><AbstractText Label="METHODS AND FINDINGS">We conducted a population-based cohort study using Danish administrative and health registries. We included individuals who tested positive for SARS-CoV-2 during the period 27 February 2020 to 29 April 2020. NSAID users (defined as individuals having filled a prescription for NSAIDs up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-users on calendar week of the test date and propensity scores based on age, sex, relevant comorbidities, and use of selected prescription drugs. The main outcome was 30-day mortality, and NSAID users were compared to non-users using risk ratios (RRs) and risk differences (RDs). Secondary outcomes included hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and acute renal replacement therapy. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion. The median age in the study cohort was 50 years, and 58% were female. Of these, 248 (2.7%) had filled a prescription for NSAIDs, and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82, p = 0.95; RD 0.1%, 95% CI -3.5% to 3.7%, p = 0.95), risk of hospitalization (RR 1.16, 95% CI 0.87 to 1.53, p = 0.31; RD 3.3%, 95% CI -3.4% to 10%, p = 0.33), ICU admission (RR 1.04, 95% CI 0.54 to 2.02, p = 0.90; RD 0.2%, 95% CI -3.0% to 3.4%, p = 0.90), mechanical ventilation (RR 1.14, 95% CI 0.56 to 2.30, p = 0.72; RD 0.5%, 95% CI -2.5% to 3.6%, p = 0.73), or renal replacement therapy (RR 0.86, 95% CI 0.24 to 3.09, p = 0.81; RD -0.2%, 95% CI -2.0% to 1.6%, p = 0.81). The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.</AbstractText><AbstractText Label="CONCLUSIONS">Use of NSAIDs was not associated with 30-day mortality, hospitalization, ICU admission, mechanical ventilation, or renal replacement therapy in Danish individuals who tested positive for SARS-CoV-2.</AbstractText><AbstractText Label="TRIAL REGISTRATION">The European Union electronic Register of Post-Authorisation Studies EUPAS34734.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lund</LastName><ForeName>Lars Christian</ForeName><Initials>LC</Initials><Identifier Source="ORCID">0000-0001-8651-6072</Identifier><AffiliationInfo><Affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kristensen</LastName><ForeName>Kasper Bruun</ForeName><Initials>KB</Initials><Identifier Source="ORCID">0000-0001-6373-1386</Identifier><AffiliationInfo><Affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reilev</LastName><ForeName>Mette</ForeName><Initials>M</Initials><Identifier Source="ORCID">0000-0003-1241-4385</Identifier><AffiliationInfo><Affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Christensen</LastName><ForeName>Steffen</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Anaesthesia and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thomsen</LastName><ForeName>Reimar Wernich</ForeName><Initials>RW</Initials><Identifier Source="ORCID">0000-0001-9135-3474</Identifier><AffiliationInfo><Affiliation>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Christiansen</LastName><ForeName>Christian Fynbo</ForeName><Initials>CF</Initials><Identifier Source="ORCID">0000-0002-0727-953X</Identifier><AffiliationInfo><Affiliation>Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Støvring</LastName><ForeName>Henrik</ForeName><Initials>H</Initials><Identifier Source="ORCID">0000-0002-5821-2351</Identifier><AffiliationInfo><Affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johansen</LastName><ForeName>Nanna Borup</ForeName><Initials>NB</Initials><Identifier Source="ORCID">0000-0003-3764-8532</Identifier><AffiliationInfo><Affiliation>Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brun</LastName><ForeName>Nikolai Constantin</ForeName><Initials>NC</Initials><AffiliationInfo><Affiliation>Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hallas</LastName><ForeName>Jesper</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0002-8097-8708</Identifier><AffiliationInfo><Affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pottegård</LastName><ForeName>Anton</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0001-9314-5679</Identifier><AffiliationInfo><Affiliation>Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS Med</MedlineTA><NlmUniqueID>101231360</NlmUniqueID><ISSNLinking>1549-1277</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000894">Anti-Inflammatory Agents, Non-Steroidal</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName><SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000894" MajorTopicYN="Y">Anti-Inflammatory Agents, Non-Steroidal</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015331" MajorTopicYN="N">Cohort Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="Y">Coronavirus Infections</DescriptorName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003718" MajorTopicYN="N" Type="Geographic">Denmark</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011307" MajorTopicYN="N">Drug Prescriptions</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006760" MajorTopicYN="N">Hospitalization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007362" MajorTopicYN="N">Intensive Care Units</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007668" MajorTopicYN="N">Kidney</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016017" MajorTopicYN="N">Odds Ratio</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D058873" MajorTopicYN="Y">Pandemics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011024" MajorTopicYN="Y">Pneumonia, Viral</DescriptorName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006435" MajorTopicYN="N">Renal Dialysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012121" MajorTopicYN="N">Respiration, Artificial</DescriptorName></MeshHeading></MeshHeadingList><CoiStatement>I have read the journal's policy and the authors of this manuscript have the following competing interests: KBK, NBJ, SC, NB, declare no conflicts of interest. RWT and CFC declare no personal conflicts of interest, yet the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study. HS reports personal fees from Bristol-Myers Squibb, personal fees from Novartis, personal fees from Roche, outside the submitted work. AP and JH report participation in research funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Servier and LEO Pharma, all with funds paid to the institution where they were employed (no personal fees) and with no relation to the work reported in this paper. LCL reports participation in research projects funded by Menarini Pharmaceutical and LEO Pharma, with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this paper. MR reports participation in research projects funded by LEO Pharma, with funds paid to the institution where she was employed (no personal fees) and with no relation to the work reported in this paper.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>9</Month><Day>8</Day><Hour>17</Hour><Minute>12</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>9</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>17</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32898149</ArticleId><ArticleId 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