Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants
•Hydroxychloroquine (HCQ) 2400 mg over 5 days was used in Belgium for COVID-19.•Impact of HCQ on mortality among 8075 patients with COVID-19 was assessed.•Lower mortality in HCQ-treated patients as compared to supportive care.•Lower mortality was irrespective of symptom duration. Hydroxychloroquine...
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| Veröffentlicht in: | International journal of antimicrobial agents 2020-10, Vol.56 (4), p.106144-106144, Article 106144 |
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| creator | Catteau, Lucy Dauby, Nicolas Montourcy, Marion Bottieau, Emmanuel Hautekiet, Joris Goetghebeur, Els van Ierssel, Sabrina Duysburgh, Els Van Oyen, Herman Wyndham-Thomas, Chloé Van Beckhoven, Dominique Bafort, Kristof Belkhir, Leïla Bossuyt, Nathalie Caprasse, Philippe Colombie, Vincent De Munter, Paul Deblonde, Jessika Delmarcelle, Didier Delvallee, Mélanie Demeester, Rémy Dugernier, Thierry Holemans, Xavier Kerzmann, Benjamin Yves Machurot, Pierre Minette, Philippe Minon, Jean-Marc Mokrane, Saphia Nachtergal, Catherine Noirhomme, Séverine Piérard, Denis Rossi, Camelia Schirvel, Carole Sermijn, Erica Staelens, Frank Triest, Filip Goethem, Nina Van Praet, Jens Van Vanhoenacker, Anke Verstraete, Roeland Willems, Elise |
| description | •Hydroxychloroquine (HCQ) 2400 mg over 5 days was used in Belgium for COVID-19.•Impact of HCQ on mortality among 8075 patients with COVID-19 was assessed.•Lower mortality in HCQ-treated patients as compared to supportive care.•Lower mortality was irrespective of symptom duration.
Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617–0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617–0.796) and aHR = 0.647 (95% CI 0.525–0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset. |
| doi_str_mv | 10.1016/j.ijantimicag.2020.106144 |
| format | Article |
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Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617–0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617–0.796) and aHR = 0.647 (95% CI 0.525–0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.</description><identifier>ISSN: 0924-8579</identifier><identifier>ISSN: 1872-7913</identifier><identifier>EISSN: 1872-7913</identifier><identifier>DOI: 10.1016/j.ijantimicag.2020.106144</identifier><identifier>PMID: 32853673</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antimalarials - therapeutic use ; Betacoronavirus - drug effects ; Betacoronavirus - pathogenicity ; C-Reactive Protein - metabolism ; Coronavirus Infections - diagnostic imaging ; Coronavirus Infections - drug therapy ; Coronavirus Infections - mortality ; Coronavirus Infections - pathology ; COVID-19 ; Disease Progression ; Drug Dosage Calculations ; Drug Repositioning ; Female ; Hospital Mortality ; Humans ; Hydroxychloroquine ; Hydroxychloroquine - therapeutic use ; Intensive Care Units ; Male ; Middle Aged ; Mortality ; Observational study ; Pandemics ; Patient Safety ; Pneumonia, Viral - diagnostic imaging ; Pneumonia, Viral - drug therapy ; Pneumonia, Viral - mortality ; Pneumonia, Viral - pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; SARS-CoV-2 ; T-Lymphocytes - pathology ; T-Lymphocytes - virology ; Tomography, X-Ray Computed ; Treatment Outcome</subject><ispartof>International journal of antimicrobial agents, 2020-10, Vol.56 (4), p.106144-106144, Article 106144</ispartof><rights>2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy</rights><rights>Copyright © 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.</rights><rights>2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-6e06d946173f60640e4c729dedbd43b268ae2f1ce10f298082bb82c93cfe53b53</citedby><cites>FETCH-LOGICAL-c483t-6e06d946173f60640e4c729dedbd43b268ae2f1ce10f298082bb82c93cfe53b53</cites><orcidid>0000-0003-4695-4275 ; 0000-0002-7697-6849</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijantimicag.2020.106144$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32853673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Catteau, Lucy</creatorcontrib><creatorcontrib>Dauby, Nicolas</creatorcontrib><creatorcontrib>Montourcy, Marion</creatorcontrib><creatorcontrib>Bottieau, Emmanuel</creatorcontrib><creatorcontrib>Hautekiet, Joris</creatorcontrib><creatorcontrib>Goetghebeur, Els</creatorcontrib><creatorcontrib>van Ierssel, Sabrina</creatorcontrib><creatorcontrib>Duysburgh, Els</creatorcontrib><creatorcontrib>Van Oyen, Herman</creatorcontrib><creatorcontrib>Wyndham-Thomas, Chloé</creatorcontrib><creatorcontrib>Van Beckhoven, Dominique</creatorcontrib><creatorcontrib>Bafort, Kristof</creatorcontrib><creatorcontrib>Belkhir, Leïla</creatorcontrib><creatorcontrib>Bossuyt, Nathalie</creatorcontrib><creatorcontrib>Caprasse, Philippe</creatorcontrib><creatorcontrib>Colombie, Vincent</creatorcontrib><creatorcontrib>De Munter, Paul</creatorcontrib><creatorcontrib>Deblonde, Jessika</creatorcontrib><creatorcontrib>Delmarcelle, Didier</creatorcontrib><creatorcontrib>Delvallee, Mélanie</creatorcontrib><creatorcontrib>Demeester, Rémy</creatorcontrib><creatorcontrib>Dugernier, Thierry</creatorcontrib><creatorcontrib>Holemans, Xavier</creatorcontrib><creatorcontrib>Kerzmann, Benjamin</creatorcontrib><creatorcontrib>Yves Machurot, Pierre</creatorcontrib><creatorcontrib>Minette, Philippe</creatorcontrib><creatorcontrib>Minon, Jean-Marc</creatorcontrib><creatorcontrib>Mokrane, Saphia</creatorcontrib><creatorcontrib>Nachtergal, Catherine</creatorcontrib><creatorcontrib>Noirhomme, Séverine</creatorcontrib><creatorcontrib>Piérard, Denis</creatorcontrib><creatorcontrib>Rossi, Camelia</creatorcontrib><creatorcontrib>Schirvel, Carole</creatorcontrib><creatorcontrib>Sermijn, Erica</creatorcontrib><creatorcontrib>Staelens, Frank</creatorcontrib><creatorcontrib>Triest, Filip</creatorcontrib><creatorcontrib>Goethem, Nina Van</creatorcontrib><creatorcontrib>Praet, Jens Van</creatorcontrib><creatorcontrib>Vanhoenacker, Anke</creatorcontrib><creatorcontrib>Verstraete, Roeland</creatorcontrib><creatorcontrib>Willems, Elise</creatorcontrib><creatorcontrib>Belgian Collaborative Group on COVID-19 Hospital Surveillance</creatorcontrib><title>Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants</title><title>International journal of antimicrobial agents</title><addtitle>Int J Antimicrob Agents</addtitle><description>•Hydroxychloroquine (HCQ) 2400 mg over 5 days was used in Belgium for COVID-19.•Impact of HCQ on mortality among 8075 patients with COVID-19 was assessed.•Lower mortality in HCQ-treated patients as compared to supportive care.•Lower mortality was irrespective of symptom duration.
Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617–0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617–0.796) and aHR = 0.647 (95% CI 0.525–0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antimalarials - therapeutic use</subject><subject>Betacoronavirus - drug effects</subject><subject>Betacoronavirus - pathogenicity</subject><subject>C-Reactive Protein - metabolism</subject><subject>Coronavirus Infections - diagnostic imaging</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - mortality</subject><subject>Coronavirus Infections - pathology</subject><subject>COVID-19</subject><subject>Disease Progression</subject><subject>Drug Dosage Calculations</subject><subject>Drug Repositioning</subject><subject>Female</subject><subject>Hospital Mortality</subject><subject>Humans</subject><subject>Hydroxychloroquine</subject><subject>Hydroxychloroquine - 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therapeutic use</topic><topic>Betacoronavirus - drug effects</topic><topic>Betacoronavirus - pathogenicity</topic><topic>C-Reactive Protein - metabolism</topic><topic>Coronavirus Infections - diagnostic imaging</topic><topic>Coronavirus Infections - drug therapy</topic><topic>Coronavirus Infections - mortality</topic><topic>Coronavirus Infections - pathology</topic><topic>COVID-19</topic><topic>Disease Progression</topic><topic>Drug Dosage Calculations</topic><topic>Drug Repositioning</topic><topic>Female</topic><topic>Hospital Mortality</topic><topic>Humans</topic><topic>Hydroxychloroquine</topic><topic>Hydroxychloroquine - therapeutic use</topic><topic>Intensive Care Units</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Observational study</topic><topic>Pandemics</topic><topic>Patient Safety</topic><topic>Pneumonia, Viral - diagnostic imaging</topic><topic>Pneumonia, Viral - drug therapy</topic><topic>Pneumonia, Viral - mortality</topic><topic>Pneumonia, Viral - pathology</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Retrospective Studies</topic><topic>SARS-CoV-2</topic><topic>T-Lymphocytes - pathology</topic><topic>T-Lymphocytes - virology</topic><topic>Tomography, X-Ray Computed</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Catteau, Lucy</creatorcontrib><creatorcontrib>Dauby, Nicolas</creatorcontrib><creatorcontrib>Montourcy, Marion</creatorcontrib><creatorcontrib>Bottieau, Emmanuel</creatorcontrib><creatorcontrib>Hautekiet, Joris</creatorcontrib><creatorcontrib>Goetghebeur, Els</creatorcontrib><creatorcontrib>van Ierssel, Sabrina</creatorcontrib><creatorcontrib>Duysburgh, Els</creatorcontrib><creatorcontrib>Van Oyen, Herman</creatorcontrib><creatorcontrib>Wyndham-Thomas, Chloé</creatorcontrib><creatorcontrib>Van Beckhoven, Dominique</creatorcontrib><creatorcontrib>Bafort, Kristof</creatorcontrib><creatorcontrib>Belkhir, Leïla</creatorcontrib><creatorcontrib>Bossuyt, Nathalie</creatorcontrib><creatorcontrib>Caprasse, Philippe</creatorcontrib><creatorcontrib>Colombie, Vincent</creatorcontrib><creatorcontrib>De Munter, Paul</creatorcontrib><creatorcontrib>Deblonde, Jessika</creatorcontrib><creatorcontrib>Delmarcelle, Didier</creatorcontrib><creatorcontrib>Delvallee, Mélanie</creatorcontrib><creatorcontrib>Demeester, Rémy</creatorcontrib><creatorcontrib>Dugernier, Thierry</creatorcontrib><creatorcontrib>Holemans, Xavier</creatorcontrib><creatorcontrib>Kerzmann, Benjamin</creatorcontrib><creatorcontrib>Yves Machurot, Pierre</creatorcontrib><creatorcontrib>Minette, Philippe</creatorcontrib><creatorcontrib>Minon, Jean-Marc</creatorcontrib><creatorcontrib>Mokrane, Saphia</creatorcontrib><creatorcontrib>Nachtergal, Catherine</creatorcontrib><creatorcontrib>Noirhomme, Séverine</creatorcontrib><creatorcontrib>Piérard, Denis</creatorcontrib><creatorcontrib>Rossi, Camelia</creatorcontrib><creatorcontrib>Schirvel, Carole</creatorcontrib><creatorcontrib>Sermijn, Erica</creatorcontrib><creatorcontrib>Staelens, Frank</creatorcontrib><creatorcontrib>Triest, Filip</creatorcontrib><creatorcontrib>Goethem, Nina Van</creatorcontrib><creatorcontrib>Praet, Jens Van</creatorcontrib><creatorcontrib>Vanhoenacker, Anke</creatorcontrib><creatorcontrib>Verstraete, Roeland</creatorcontrib><creatorcontrib>Willems, Elise</creatorcontrib><creatorcontrib>Belgian Collaborative Group on COVID-19 Hospital Surveillance</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of antimicrobial agents</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Catteau, Lucy</au><au>Dauby, Nicolas</au><au>Montourcy, Marion</au><au>Bottieau, Emmanuel</au><au>Hautekiet, Joris</au><au>Goetghebeur, Els</au><au>van Ierssel, Sabrina</au><au>Duysburgh, Els</au><au>Van Oyen, Herman</au><au>Wyndham-Thomas, Chloé</au><au>Van Beckhoven, Dominique</au><au>Bafort, Kristof</au><au>Belkhir, Leïla</au><au>Bossuyt, Nathalie</au><au>Caprasse, Philippe</au><au>Colombie, Vincent</au><au>De Munter, Paul</au><au>Deblonde, Jessika</au><au>Delmarcelle, Didier</au><au>Delvallee, Mélanie</au><au>Demeester, Rémy</au><au>Dugernier, Thierry</au><au>Holemans, Xavier</au><au>Kerzmann, Benjamin</au><au>Yves Machurot, Pierre</au><au>Minette, Philippe</au><au>Minon, Jean-Marc</au><au>Mokrane, Saphia</au><au>Nachtergal, Catherine</au><au>Noirhomme, Séverine</au><au>Piérard, Denis</au><au>Rossi, Camelia</au><au>Schirvel, Carole</au><au>Sermijn, Erica</au><au>Staelens, Frank</au><au>Triest, Filip</au><au>Goethem, Nina Van</au><au>Praet, Jens Van</au><au>Vanhoenacker, Anke</au><au>Verstraete, Roeland</au><au>Willems, Elise</au><aucorp>Belgian Collaborative Group on COVID-19 Hospital Surveillance</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants</atitle><jtitle>International journal of antimicrobial agents</jtitle><addtitle>Int J Antimicrob Agents</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>56</volume><issue>4</issue><spage>106144</spage><epage>106144</epage><pages>106144-106144</pages><artnum>106144</artnum><issn>0924-8579</issn><issn>1872-7913</issn><eissn>1872-7913</eissn><abstract>•Hydroxychloroquine (HCQ) 2400 mg over 5 days was used in Belgium for COVID-19.•Impact of HCQ on mortality among 8075 patients with COVID-19 was assessed.•Lower mortality in HCQ-treated patients as compared to supportive care.•Lower mortality was irrespective of symptom duration.
Hydroxychloroquine (HCQ) has been largely used and investigated as therapy for COVID-19 across various settings at a total dose usually ranging from 2400 mg to 9600 mg. In Belgium, off-label use of low-dose HCQ (total 2400 mg over 5 days) was recommended for hospitalised patients with COVID-19. We conducted a retrospective analysis of in-hospital mortality in the Belgian national COVID-19 hospital surveillance data. Patients treated either with HCQ monotherapy and supportive care (HCQ group) were compared with patients treated with supportive care only (no-HCQ group) using a competing risks proportional hazards regression with discharge alive as competing risk, adjusted for demographic and clinical features with robust standard errors. Of 8075 patients with complete discharge data on 24 May 2020 and diagnosed before 1 May 2020, 4542 received HCQ in monotherapy and 3533 were in the no-HCQ group. Death was reported in 804/4542 (17.7%) and 957/3533 (27.1%), respectively. In the multivariable analysis, mortality was lower in the HCQ group compared with the no-HCQ group [adjusted hazard ratio (aHR) = 0.684, 95% confidence interval (CI) 0.617–0.758]. Compared with the no-HCQ group, mortality in the HCQ group was reduced both in patients diagnosed ≤5 days (n = 3975) and >5 days (n = 3487) after symptom onset [aHR = 0.701 (95% CI 0.617–0.796) and aHR = 0.647 (95% CI 0.525–0.797), respectively]. Compared with supportive care only, low-dose HCQ monotherapy was independently associated with lower mortality in hospitalised patients with COVID-19 diagnosed and treated early or later after symptom onset.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>32853673</pmid><doi>10.1016/j.ijantimicag.2020.106144</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-4695-4275</orcidid><orcidid>https://orcid.org/0000-0002-7697-6849</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0924-8579 |
| ispartof | International journal of antimicrobial agents, 2020-10, Vol.56 (4), p.106144-106144, Article 106144 |
| issn | 0924-8579 1872-7913 1872-7913 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7444610 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescent Adult Aged Aged, 80 and over Antimalarials - therapeutic use Betacoronavirus - drug effects Betacoronavirus - pathogenicity C-Reactive Protein - metabolism Coronavirus Infections - diagnostic imaging Coronavirus Infections - drug therapy Coronavirus Infections - mortality Coronavirus Infections - pathology COVID-19 Disease Progression Drug Dosage Calculations Drug Repositioning Female Hospital Mortality Humans Hydroxychloroquine Hydroxychloroquine - therapeutic use Intensive Care Units Male Middle Aged Mortality Observational study Pandemics Patient Safety Pneumonia, Viral - diagnostic imaging Pneumonia, Viral - drug therapy Pneumonia, Viral - mortality Pneumonia, Viral - pathology Prognosis Proportional Hazards Models Retrospective Studies SARS-CoV-2 T-Lymphocytes - pathology T-Lymphocytes - virology Tomography, X-Ray Computed Treatment Outcome |
| title | Low-dose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants |
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