Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospita...

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Veröffentlicht in:The Journal of clinical investigation 2020-12, Vol.130 (12), p.6417-6428
Hauptverfasser: Liu, Jiao, Zhang, Sheng, Dong, Xuan, Li, Zhongyi, Xu, Qianghong, Feng, Huibin, Cai, Jing, Huang, Sisi, Guo, Jun, Zhang, Lidi, Chen, Yizhu, Zhu, Wei, Du, Hangxiang, Liu, Yongan, Wang, Tao, Chen, Limin, Wen, Zhenliang, Annane, Djillali, Qu, Jieming, Chen, Dechang
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container_end_page 6428
container_issue 12
container_start_page 6417
container_title The Journal of clinical investigation
container_volume 130
creator Liu, Jiao
Zhang, Sheng
Dong, Xuan
Li, Zhongyi
Xu, Qianghong
Feng, Huibin
Cai, Jing
Huang, Sisi
Guo, Jun
Zhang, Lidi
Chen, Yizhu
Zhu, Wei
Du, Hangxiang
Liu, Yongan
Wang, Tao
Chen, Limin
Wen, Zhenliang
Annane, Djillali
Qu, Jieming
Chen, Dechang
description BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.
doi_str_mv 10.1172/JCI140617
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Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P &lt; 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P &lt; 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P &lt; 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (&gt;200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI140617</identifier><identifier>PMID: 33141117</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Adrenal Cortex Hormones - administration &amp; dosage ; Adrenal Cortex Hormones - adverse effects ; Adult respiratory distress syndrome ; Aged ; Biomedical research ; Clinical Medicine ; Complications and side effects ; Coronaviridae ; Coronaviruses ; Corticosteroid drugs ; Corticosteroids ; COVID-19 ; COVID-19 - complications ; COVID-19 - drug therapy ; COVID-19 - mortality ; Disease-Free Survival ; Dosage and administration ; Drug dosages ; Drug therapy ; Female ; Genetic aspects ; Health aspects ; Hospitalization ; Humans ; Life Sciences ; Male ; Mechanical ventilation ; Middle Aged ; Mortality ; Patient outcomes ; Patients ; Respiratory diseases ; Respiratory distress syndrome ; Respiratory Distress Syndrome - drug therapy ; Respiratory Distress Syndrome - etiology ; Respiratory Distress Syndrome - mortality ; Retrospective Studies ; Ribonucleic acid ; RNA ; Severe acute respiratory syndrome coronavirus 2 ; Severity of Illness Index ; Survival Rate ; Ventilators ; Vital signs</subject><ispartof>The Journal of clinical investigation, 2020-12, Vol.130 (12), p.6417-6428</ispartof><rights>COPYRIGHT 2020 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Dec 2020</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2020 American Society for Clinical Investigation 2020 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-540092e93ce1d680f21c3ced6bedb459d31d4fd49b69c01c238e8c86730025213</citedby><cites>FETCH-LOGICAL-c641t-540092e93ce1d680f21c3ced6bedb459d31d4fd49b69c01c238e8c86730025213</cites><orcidid>0000-0001-5116-1099 ; 0000-0001-6805-8944 ; 0000-0002-6589-4151 ; 0000-0002-4765-9377</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685724/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685724/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33141117$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03109201$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Jiao</creatorcontrib><creatorcontrib>Zhang, Sheng</creatorcontrib><creatorcontrib>Dong, Xuan</creatorcontrib><creatorcontrib>Li, Zhongyi</creatorcontrib><creatorcontrib>Xu, Qianghong</creatorcontrib><creatorcontrib>Feng, Huibin</creatorcontrib><creatorcontrib>Cai, Jing</creatorcontrib><creatorcontrib>Huang, Sisi</creatorcontrib><creatorcontrib>Guo, Jun</creatorcontrib><creatorcontrib>Zhang, Lidi</creatorcontrib><creatorcontrib>Chen, Yizhu</creatorcontrib><creatorcontrib>Zhu, Wei</creatorcontrib><creatorcontrib>Du, Hangxiang</creatorcontrib><creatorcontrib>Liu, Yongan</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Chen, Limin</creatorcontrib><creatorcontrib>Wen, Zhenliang</creatorcontrib><creatorcontrib>Annane, Djillali</creatorcontrib><creatorcontrib>Qu, Jieming</creatorcontrib><creatorcontrib>Chen, Dechang</creatorcontrib><title>Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P &lt; 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P &lt; 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P &lt; 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (&gt;200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.</description><subject>Adrenal Cortex Hormones - administration &amp; dosage</subject><subject>Adrenal Cortex Hormones - adverse effects</subject><subject>Adult respiratory distress syndrome</subject><subject>Aged</subject><subject>Biomedical research</subject><subject>Clinical Medicine</subject><subject>Complications and side effects</subject><subject>Coronaviridae</subject><subject>Coronaviruses</subject><subject>Corticosteroid drugs</subject><subject>Corticosteroids</subject><subject>COVID-19</subject><subject>COVID-19 - complications</subject><subject>COVID-19 - drug therapy</subject><subject>COVID-19 - mortality</subject><subject>Disease-Free Survival</subject><subject>Dosage and administration</subject><subject>Drug dosages</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hospitalization</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mechanical ventilation</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Respiratory diseases</subject><subject>Respiratory distress syndrome</subject><subject>Respiratory Distress Syndrome - drug therapy</subject><subject>Respiratory Distress Syndrome - etiology</subject><subject>Respiratory Distress Syndrome - mortality</subject><subject>Retrospective Studies</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Severity of Illness Index</subject><subject>Survival Rate</subject><subject>Ventilators</subject><subject>Vital 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Jiao</creator><creator>Zhang, Sheng</creator><creator>Dong, Xuan</creator><creator>Li, Zhongyi</creator><creator>Xu, Qianghong</creator><creator>Feng, Huibin</creator><creator>Cai, Jing</creator><creator>Huang, Sisi</creator><creator>Guo, Jun</creator><creator>Zhang, Lidi</creator><creator>Chen, Yizhu</creator><creator>Zhu, Wei</creator><creator>Du, Hangxiang</creator><creator>Liu, Yongan</creator><creator>Wang, Tao</creator><creator>Chen, Limin</creator><creator>Wen, Zhenliang</creator><creator>Annane, Djillali</creator><creator>Qu, Jieming</creator><creator>Chen, Dechang</creator><general>American Society for Clinical 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treatment in severe COVID-19 patients with acute respiratory distress syndrome</title><author>Liu, Jiao ; Zhang, Sheng ; Dong, Xuan ; Li, Zhongyi ; Xu, Qianghong ; Feng, Huibin ; Cai, Jing ; Huang, Sisi ; Guo, Jun ; Zhang, Lidi ; Chen, Yizhu ; Zhu, Wei ; Du, Hangxiang ; Liu, Yongan ; Wang, Tao ; Chen, Limin ; Wen, Zhenliang ; Annane, Djillali ; Qu, Jieming ; Chen, Dechang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-540092e93ce1d680f21c3ced6bedb459d31d4fd49b69c01c238e8c86730025213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adrenal Cortex Hormones - administration &amp; dosage</topic><topic>Adrenal Cortex Hormones - adverse effects</topic><topic>Adult respiratory distress syndrome</topic><topic>Aged</topic><topic>Biomedical research</topic><topic>Clinical Medicine</topic><topic>Complications and side effects</topic><topic>Coronaviridae</topic><topic>Coronaviruses</topic><topic>Corticosteroid drugs</topic><topic>Corticosteroids</topic><topic>COVID-19</topic><topic>COVID-19 - complications</topic><topic>COVID-19 - drug therapy</topic><topic>COVID-19 - mortality</topic><topic>Disease-Free Survival</topic><topic>Dosage and administration</topic><topic>Drug dosages</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hospitalization</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mechanical ventilation</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Respiratory diseases</topic><topic>Respiratory distress syndrome</topic><topic>Respiratory Distress Syndrome - drug therapy</topic><topic>Respiratory Distress Syndrome - etiology</topic><topic>Respiratory Distress Syndrome - mortality</topic><topic>Retrospective Studies</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Severity of Illness Index</topic><topic>Survival Rate</topic><topic>Ventilators</topic><topic>Vital signs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jiao</creatorcontrib><creatorcontrib>Zhang, Sheng</creatorcontrib><creatorcontrib>Dong, Xuan</creatorcontrib><creatorcontrib>Li, Zhongyi</creatorcontrib><creatorcontrib>Xu, Qianghong</creatorcontrib><creatorcontrib>Feng, Huibin</creatorcontrib><creatorcontrib>Cai, Jing</creatorcontrib><creatorcontrib>Huang, Sisi</creatorcontrib><creatorcontrib>Guo, Jun</creatorcontrib><creatorcontrib>Zhang, Lidi</creatorcontrib><creatorcontrib>Chen, Yizhu</creatorcontrib><creatorcontrib>Zhu, Wei</creatorcontrib><creatorcontrib>Du, Hangxiang</creatorcontrib><creatorcontrib>Liu, Yongan</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Chen, Limin</creatorcontrib><creatorcontrib>Wen, Zhenliang</creatorcontrib><creatorcontrib>Annane, Djillali</creatorcontrib><creatorcontrib>Qu, Jieming</creatorcontrib><creatorcontrib>Chen, Dechang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech 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Sheng</au><au>Dong, Xuan</au><au>Li, Zhongyi</au><au>Xu, Qianghong</au><au>Feng, Huibin</au><au>Cai, Jing</au><au>Huang, Sisi</au><au>Guo, Jun</au><au>Zhang, Lidi</au><au>Chen, Yizhu</au><au>Zhu, Wei</au><au>Du, Hangxiang</au><au>Liu, Yongan</au><au>Wang, Tao</au><au>Chen, Limin</au><au>Wen, Zhenliang</au><au>Annane, Djillali</au><au>Qu, Jieming</au><au>Chen, Dechang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>130</volume><issue>12</issue><spage>6417</spage><epage>6428</epage><pages>6417-6428</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P &lt; 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P &lt; 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P &lt; 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (&gt;200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>33141117</pmid><doi>10.1172/JCI140617</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-5116-1099</orcidid><orcidid>https://orcid.org/0000-0001-6805-8944</orcidid><orcidid>https://orcid.org/0000-0002-6589-4151</orcidid><orcidid>https://orcid.org/0000-0002-4765-9377</orcidid><oa>free_for_read</oa></addata></record>
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ispartof The Journal of clinical investigation, 2020-12, Vol.130 (12), p.6417-6428
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subjects Adrenal Cortex Hormones - administration & dosage
Adrenal Cortex Hormones - adverse effects
Adult respiratory distress syndrome
Aged
Biomedical research
Clinical Medicine
Complications and side effects
Coronaviridae
Coronaviruses
Corticosteroid drugs
Corticosteroids
COVID-19
COVID-19 - complications
COVID-19 - drug therapy
COVID-19 - mortality
Disease-Free Survival
Dosage and administration
Drug dosages
Drug therapy
Female
Genetic aspects
Health aspects
Hospitalization
Humans
Life Sciences
Male
Mechanical ventilation
Middle Aged
Mortality
Patient outcomes
Patients
Respiratory diseases
Respiratory distress syndrome
Respiratory Distress Syndrome - drug therapy
Respiratory Distress Syndrome - etiology
Respiratory Distress Syndrome - mortality
Retrospective Studies
Ribonucleic acid
RNA
Severe acute respiratory syndrome coronavirus 2
Severity of Illness Index
Survival Rate
Ventilators
Vital signs
title Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome
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