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Research
hongshan chen
Nanjing Medical University
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background
COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover a sensitive and reliable early-warning biomarker for optimizing management and improving the prognosis of COVID-19 patients.
Methods
A total of 2,954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this selected retrospectively cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were also recorded. Single-cell RNA-sequencing of cells was performed to analyze SARS-CoV-2 receptor expression.
Results
Among 2,954 COVID-19 patients in the final analysis, the median age was 60 years (50–68 years), 1,461 (49.5%) were female, and 1,515 (51.3%) were severe/critical. Compared to mild/moderate (1,439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with elevated BNP levels were at a higher risk of death (hazards ratio, 1.001 [95% CI, 1.0003–1.002]).
Conclusions
COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. Brain natriuretic peptide is an effective biomarker for risk assessment in COVID-19 patients with or without pre-existing CAD.
Keywords
COVID-19, Brain natriuretic peptide, SARS-CoV-2 receptor
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CURRENT STATUS: Under Review
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Posted 08 Feb, 2021
Reviewer #4 agreed
On 08 Feb, 2021
Reviewer #2 agreed
On 07 Feb, 2021
Reviewer #3 agreed
On 07 Feb, 2021
Editor assigned
On 07 Feb, 2021
Reviewers invited
Invitations sent on 07 Feb, 2021
Reviewer #1 agreed
On 07 Feb, 2021
Submission checks complete
On 07 Feb, 2021
Editor invited
On 07 Feb, 2021
This version was not preprinted
Version 1
Posted 23 Dec, 2020
No community comments so far
Review #4 received
Received 02 Jan, 2021
Editorial decision: Major revision
On 02 Jan, 2021
Review #1 received
Received 01 Jan, 2021
Review #3 received
Received 30 Dec, 2020
Review #2 received
Received 30 Dec, 2020
Reviewer #4 agreed
On 23 Dec, 2020
Reviewer #3 agreed
On 22 Dec, 2020
Reviewer #2 agreed
On 22 Dec, 2020
Reviewer #1 agreed
On 21 Dec, 2020
Editor invited
On 20 Dec, 2020
Reviewers invited
Invitations sent on 20 Dec, 2020
Editor assigned
On 19 Dec, 2020
Submission checks complete
On 19 Dec, 2020
First submitted
On 16 Dec, 2020
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This preprint is under consideration at Critical Care. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
hongshan chen
Nanjing Medical University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 08 Feb, 2021
Reviewer #4 agreed
On 08 Feb, 2021
Reviewer #2 agreed
On 07 Feb, 2021
Reviewer #3 agreed
On 07 Feb, 2021
Editor assigned
On 07 Feb, 2021
Reviewers invited
Invitations sent on 07 Feb, 2021
Reviewer #1 agreed
On 07 Feb, 2021
Submission checks complete
On 07 Feb, 2021
Editor invited
On 07 Feb, 2021
This version was not preprinted
Version 1
Posted 23 Dec, 2020
No community comments so far
Review #4 received
Received 02 Jan, 2021
Editorial decision: Major revision
On 02 Jan, 2021
Review #1 received
Received 01 Jan, 2021
Review #3 received
Received 30 Dec, 2020
Review #2 received
Received 30 Dec, 2020
Reviewer #4 agreed
On 23 Dec, 2020
Reviewer #3 agreed
On 22 Dec, 2020
Reviewer #2 agreed
On 22 Dec, 2020
Reviewer #1 agreed
On 21 Dec, 2020
Editor invited
On 20 Dec, 2020
Reviewers invited
Invitations sent on 20 Dec, 2020
Editor assigned
On 19 Dec, 2020
Submission checks complete
On 19 Dec, 2020
First submitted
On 16 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover a sensitive and reliable early-warning biomarker for optimizing management and improving the prognosis of COVID-19 patients.
Methods
A total of 2,954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this selected retrospectively cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were also recorded. Single-cell RNA-sequencing of cells was performed to analyze SARS-CoV-2 receptor expression.
Results
Among 2,954 COVID-19 patients in the final analysis, the median age was 60 years (50–68 years), 1,461 (49.5%) were female, and 1,515 (51.3%) were severe/critical. Compared to mild/moderate (1,439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with elevated BNP levels were at a higher risk of death (hazards ratio, 1.001 [95% CI, 1.0003–1.002]).
Conclusions
COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. Brain natriuretic peptide is an effective biomarker for risk assessment in COVID-19 patients with or without pre-existing CAD.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
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