ABSTRACT
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.
Subject(s)
COVID-19 , Coronary Artery DiseaseABSTRACT
Background: Coronavirus disease (COVID-19) has resulted in high mortality worldwide. However, information regarding cardiac markers for precise risk-stratification is limited. We aimed to discover a sensitive and reliable early-warning biomarker for optimizing management and improving COVID-19 patients’ prognosis. Methods: This single-center case series was conducted between February 4 and April 10, 2020. In total, 2,954 consecutive COVID-19 patients who were receiving treatment at Wuhan Huoshenshan Hospital in China were included in the retrospectively selected cohort. All patients were diagnosed with COVID-19 and treated at the study site. Data of serum levels of cardiac markers, coronary artery disease (CAD) diagnosis, and survival were collected after admission. Single-cell RNA-sequencing was performed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression.Findings: Median patient age was 60 years (range, 50-68 years); 1,461 (49.5%) were female, and 1,515 (51.3%) patients were in a severe/critical condition. Compared to mild/moderate patients (1,439, 48.7%), severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. Among severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide had a significantly higher mortality rate than patients with normal levels. Severe/critical COVID-19 patients with pre-existing CAD (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide levels than those without CAD. Enhanced SARS-CoV-2 receptor expression was observed in patients with CAD. Regression analysis revealed that patients with elevated brain natriuretic peptide levels were at a higher risk of death (hazards ratio, 1.001 [95% confidence interval, 1.0003-1.002]).Interpretation: Brain natriuretic peptide is an effective biomarker for risk assessment in COVID-19 patients with or without pre-existing CAD. The detection of BNP is widely used in clinical practice and can be easily implemented in hospitals at all levels.Funding Statement: This research was supported by grants from National Nature Science Foundation of China (Grant No. 31771334, 81970428, 91959113, 81972358, 81572893), the Key Research Plan of the National Natural Science Foundation of China (Grant No. 81820108002), the Major Research Plan of the National Natural Science Foundation of China (Grant No. 91649125, 91639204), Key Foundation of Wuhan Huoshenshan Hospital (Grant No. 2020[18]), Key Research & Development Program of Jiangsu Province (Grant Nos. BE2017733, BE2018713), Medical Innovation Project of Logistics Service (Grant No. 18JS005), Basic Research Program of Jiangsu Province (Grant No. BK20180036), and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No.18KJB180014).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study design was approved by the institutional ethics board. Written informed consent was waived due to the urgency of the COVID-19 pandemic.
Subject(s)
Coronavirus Infections , Coronary Artery Disease , COVID-19ABSTRACT
Background: Coronavirus disease (COVID-19) has resulted in high mortality worldwide. However, information regarding cardiac markers for precise risk-stratification is limited. We aimed to discover a sensitive and reliable early-warning biomarker for optimizing management and improving COVID-19 patients’ prognosis. Methods: This single-center case series was conducted between February 4 and April 10, 2020. In total, 2,954 consecutive COVID-19 patients who were receiving treatment at Wuhan Huoshenshan Hospital in China were included in the retrospectively selected cohort. All patients were diagnosed with COVID-19 and treated at the study site. Data of serum levels of cardiac markers, coronary artery disease (CAD) diagnosis, and survival were collected after admission. Single-cell RNA-sequencing was performed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression.Results: Median patient age was 60 years (range, 50-68 years); 1,461 (49.5%) were female, and 1,515 (51.3%) patients were in a severe/critical condition. Compared to mild/moderate patients (1,439, 48.7%), severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. Among severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide had a significantly higher mortality rate than patients with normal levels. Severe/critical COVID-19 patients with pre-existing CAD (165/1,155 [10.9%]) had more cases of abnormal brain natriuretic peptide levels than those without CAD. Enhanced SARS-CoV-2 receptor expression was observed in patients with CAD. Regression analysis revealed that patients with elevated brain natriuretic peptide levels were at a higher risk of death (hazards ratio, 1.001 [95% confidence interval, 1.0003-1.002]). Conclusions: Brain natriuretic peptide is an effective biomarker for early risk assessment in COVID-19 patients with or without pre-existing CAD. Monitoring BNP status will improve the risk-stratification management and prognosis of patients within one week after admission.
Subject(s)
COVID-19 , Death , Coronary Artery DiseaseABSTRACT
Background Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take sex as consideration.Methods We performed an unbiased sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and SARS-CoV-2 specific antibody levels of 1,558 males and 1,499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. Total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.Results We found that the mortality and ICU admission rates were approximately 2-fold higher in males than that in females (P < 0.005). Survival analysis revealed that sex is an independent prognostic factor for COVID-19 (Hazard ratio = 2.2, P = 0.003). The concentration of inflammatory factors in peripheral blood was significantly higher in males. Besides, the renal and hepatic abnormality induced by COVID-19 was more common in males during the hospitalization. The analysis of lymphocyte subsets revealed that the percentage of CD19 + B cell and CD4 + T cell was significantly higher in females (P < 0.001) during hospitalization, indicating the stronger humoral immunity in females than males. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in females, while gradually increased and reached a peak in the seventh week in males.Conclusions The unfavorable prognosis of male COVID-19 patients may result from the weak humoral immunity and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients. Convalescent plasma therapy may help improve the immunity of males to fight against SARS-CoV-2 infection.