Serveur d'exploration sur la COVID chez les séniors

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Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19 patients with no prior cardiovascular disease.

Identifieur interne : 000416 ( Main/Exploration ); précédent : 000415; suivant : 000417

Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19 patients with no prior cardiovascular disease.

Auteurs : Jiatian Cao [République populaire de Chine] ; Yan Zheng [République populaire de Chine] ; Zhe Luo [République populaire de Chine] ; Zhendong Mei [République populaire de Chine] ; Yumeng Yao [République populaire de Chine] ; Zilong Liu [République populaire de Chine] ; Chao Liang [République populaire de Chine] ; Hongbo Yang [République populaire de Chine] ; Yanan Song [République populaire de Chine] ; Kaihuan Yu [République populaire de Chine] ; Yan Gao [République populaire de Chine] ; Chouwen Zhu [République populaire de Chine] ; Zheyong Huang [République populaire de Chine] ; Juying Qian [République populaire de Chine] ; Junbo Ge [République populaire de Chine]

Source :

RBID : pubmed:32863952

Descripteurs français

English descriptors

Abstract

Introduction: To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality. Methods: We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis. Results: In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions, P for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72), P=0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91), P=0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality. Conclusions: In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19.

DOI: 10.7150/thno.47980
PubMed: 32863952
PubMed Central: PMC7449913


Affiliations:


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<name sortKey="Liu, Zilong" sort="Liu, Zilong" uniqKey="Liu Z" first="Zilong" last="Liu">Zilong Liu</name>
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<country xml:lang="fr">République populaire de Chine</country>
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<wicri:regionArea>Department of Neurology, Remin Hospital of Wuhan University, 99 Ziyang Road,Wuchang District, Wuhan 430200</wicri:regionArea>
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<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
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<name sortKey="Qian, Juying" sort="Qian, Juying" uniqKey="Qian J" first="Juying" last="Qian">Juying Qian</name>
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<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
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<name sortKey="Ge, Junbo" sort="Ge, Junbo" uniqKey="Ge J" first="Junbo" last="Ge">Junbo Ge</name>
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<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
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<author>
<name sortKey="Cao, Jiatian" sort="Cao, Jiatian" uniqKey="Cao J" first="Jiatian" last="Cao">Jiatian Cao</name>
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<nlm:affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
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<name sortKey="Zheng, Yan" sort="Zheng, Yan" uniqKey="Zheng Y" first="Yan" last="Zheng">Yan Zheng</name>
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<nlm:affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
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<nlm:affiliation>State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438</wicri:regionArea>
<wicri:noRegion>Shanghai 200438</wicri:noRegion>
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<affiliation wicri:level="1">
<nlm:affiliation>Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, 200438 China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai</wicri:regionArea>
<wicri:noRegion>Shanghai</wicri:noRegion>
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<name sortKey="Luo, Zhe" sort="Luo, Zhe" uniqKey="Luo Z" first="Zhe" last="Luo">Zhe Luo</name>
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<nlm:affiliation>Department of Critical Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Critical Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Mei, Zhendong" sort="Mei, Zhendong" uniqKey="Mei Z" first="Zhendong" last="Mei">Zhendong Mei</name>
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<nlm:affiliation>State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438</wicri:regionArea>
<wicri:noRegion>Shanghai 200438</wicri:noRegion>
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<author>
<name sortKey="Yao, Yumeng" sort="Yao, Yumeng" uniqKey="Yao Y" first="Yumeng" last="Yao">Yumeng Yao</name>
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<nlm:affiliation>Department of Infectious Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
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<name sortKey="Liu, Zilong" sort="Liu, Zilong" uniqKey="Liu Z" first="Zilong" last="Liu">Zilong Liu</name>
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<nlm:affiliation>Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liang, Chao" sort="Liang, Chao" uniqKey="Liang C" first="Chao" last="Liang">Chao Liang</name>
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<nlm:affiliation>Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yang, Hongbo" sort="Yang, Hongbo" uniqKey="Yang H" first="Hongbo" last="Yang">Hongbo Yang</name>
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<nlm:affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Song, Yanan" sort="Song, Yanan" uniqKey="Song Y" first="Yanan" last="Song">Yanan Song</name>
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<nlm:affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
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<author>
<name sortKey="Yu, Kaihuan" sort="Yu, Kaihuan" uniqKey="Yu K" first="Kaihuan" last="Yu">Kaihuan Yu</name>
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<nlm:affiliation>Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University. Gaoxin 6th Road, Donghu high tech Development Zone, Wuhan 430200, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University. Gaoxin 6th Road, Donghu high tech Development Zone, Wuhan 430200</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<name sortKey="Gao, Yan" sort="Gao, Yan" uniqKey="Gao Y" first="Yan" last="Gao">Yan Gao</name>
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<nlm:affiliation>Department of Neurology, Remin Hospital of Wuhan University, 99 Ziyang Road,Wuchang District, Wuhan 430200, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurology, Remin Hospital of Wuhan University, 99 Ziyang Road,Wuchang District, Wuhan 430200</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<name sortKey="Zhu, Chouwen" sort="Zhu, Chouwen" uniqKey="Zhu C" first="Chouwen" last="Zhu">Chouwen Zhu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Gastroenterology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Gastroenterology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Huang, Zheyong" sort="Huang, Zheyong" uniqKey="Huang Z" first="Zheyong" last="Huang">Zheyong Huang</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Qian, Juying" sort="Qian, Juying" uniqKey="Qian J" first="Juying" last="Qian">Juying Qian</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032</wicri:regionArea>
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<term>Cardiomyopathies (blood)</term>
<term>Cardiomyopathies (etiology)</term>
<term>China (MeSH)</term>
<term>Cohort Studies (MeSH)</term>
<term>Coronavirus Infections (blood)</term>
<term>Coronavirus Infections (complications)</term>
<term>Coronavirus Infections (mortality)</term>
<term>Female (MeSH)</term>
<term>Hospitalization (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (blood)</term>
<term>Pneumonia, Viral (complications)</term>
<term>Pneumonia, Viral (mortality)</term>
<term>Predictive Value of Tests (MeSH)</term>
<term>Prognosis (MeSH)</term>
<term>Retrospective Studies (MeSH)</term>
<term>Troponin I (blood)</term>
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<term>Adulte d'âge moyen (MeSH)</term>
<term>Cardiomyopathies (sang)</term>
<term>Cardiomyopathies (étiologie)</term>
<term>Chine (MeSH)</term>
<term>Femelle (MeSH)</term>
<term>Hospitalisation (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Infections à coronavirus (complications)</term>
<term>Infections à coronavirus (mortalité)</term>
<term>Infections à coronavirus (sang)</term>
<term>Mâle (MeSH)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (complications)</term>
<term>Pneumopathie virale (mortalité)</term>
<term>Pneumopathie virale (sang)</term>
<term>Pronostic (MeSH)</term>
<term>Sujet âgé (MeSH)</term>
<term>Troponine I (sang)</term>
<term>Valeur prédictive des tests (MeSH)</term>
<term>Études de cohortes (MeSH)</term>
<term>Études rétrospectives (MeSH)</term>
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<term>China</term>
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<term>Pneumonia, Viral</term>
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<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
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<term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
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<term>Cardiomyopathies</term>
<term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
<term>Troponine I</term>
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<front>
<div type="abstract" xml:lang="en">
<b>Introduction:</b>
To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality.
<b>Methods:</b>
We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis.
<b>Results:</b>
In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions,
<i>P</i>
for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72),
<i>P</i>
=0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91),
<i>P</i>
=0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality.
<b>Conclusions:</b>
In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19.</div>
</front>
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<Year>2020</Year>
<Month>09</Month>
<Day>14</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>09</Month>
<Day>14</Day>
</DateRevised>
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<ISSN IssnType="Electronic">1838-7640</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>10</Volume>
<Issue>21</Issue>
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<Year>2020</Year>
</PubDate>
</JournalIssue>
<Title>Theranostics</Title>
<ISOAbbreviation>Theranostics</ISOAbbreviation>
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<ArticleTitle>Myocardial injury and COVID-19: Serum hs-cTnI level in risk stratification and the prediction of 30-day fatality in COVID-19 patients with no prior cardiovascular disease.</ArticleTitle>
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<ELocationID EIdType="doi" ValidYN="Y">10.7150/thno.47980</ELocationID>
<Abstract>
<AbstractText>
<b>Introduction:</b>
To explore the involvement of the cardiovascular system in coronavirus disease 2019 (COVID-19), we investigated whether myocardial injury occurred in COVID-19 patients and assessed the performance of serum high-sensitivity cardiac Troponin I (hs-cTnI) levels in predicting disease severity and 30-day in-hospital fatality.
<b>Methods:</b>
We included 244 COVID-19 patients, who were admitted to Renmin Hospital of Wuhan University with no preexisting cardiovascular disease or renal dysfunction. We analyzed the data including patients' clinical characteristics, cardiac biomarkers, severity of medical conditions, and 30-day in-hospital fatality. We performed multivariable Cox regressions and the receiver operating characteristic analysis to assess the association of cardiac biomarkers on admission with disease severity and prognosis.
<b>Results:</b>
In this retrospective observational study, 11% of COVID-19 patients had increased hs-cTnI levels (>40 ng/L) on admission. Of note, serum hs-cTnI levels were positively associated with the severity of medical conditions (median [interquartile range (IQR)]: 6.00 [6.00-6.00] ng/L in 91 patients with moderate conditions, 6.00 [6.00-18.00] ng/L in 107 patients with severe conditions, and 11.00 [6.00-56.75] ng/L in 46 patients with critical conditions,
<i>P</i>
for trend=0.001). Moreover, compared with those with normal cTnI levels, patients with increased hs-cTnI levels had higher in-hospital fatality (adjusted hazard ratio [95% CI]: 4.79 [1.46-15.69]). The receiver-operating characteristic curve analysis suggested that the inclusion of hs-cTnI levels into a panel of empirical prognostic factors substantially improved the prediction performance for severe or critical conditions (area under the curve (AUC): 0.71 (95% CI: 0.65-0.78) vs. 0.65 (0.58-0.72),
<i>P</i>
=0.01), as well as for 30-day fatality (AUC: 0.91 (0.85-0.96) vs. 0.77 (0.62-0.91),
<i>P</i>
=0.04). A cutoff value of 20 ng/L of hs-cTnI level led to the best prediction to 30-day fatality.
<b>Conclusions:</b>
In COVID-19 patients with no preexisting cardiovascular disease, 11% had increased hs-cTnI levels. Besides empirical prognostic factors, serum hs-cTnI levels upon admission provided independent prediction to both the severity of the medical condition and 30-day in-hospital fatality. These findings may shed important light on the clinical management of COVID-19.</AbstractText>
<CopyrightInformation>© The author(s).</CopyrightInformation>
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<LastName>Cao</LastName>
<ForeName>Jiatian</ForeName>
<Initials>J</Initials>
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<Affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y">
<LastName>Zheng</LastName>
<ForeName>Yan</ForeName>
<Initials>Y</Initials>
<AffiliationInfo>
<Affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.</Affiliation>
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<Affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</Affiliation>
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<LastName>Ge</LastName>
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<Affiliation>Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases. 180 Feng Lin Road, Shanghai 200032, China.</Affiliation>
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