Background and Purpose: 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. Experiments Approach: This retrospectively single-center case series was conducted between February 4 and April 10, 2020. 3,046 consecutive COVID-19 patients who were receiving treatment at Wuhan Huoshenshan Hospital in China were included. Serum levels of cardiac markers and coronary artery disease (CAD) diagnosis were collected after admission. Single-cell RNA-sequencing was performed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression. Key Results: Median patient age was 60 years; 1,461 (49.5%) were female, and 1,515 (51.3%) were in a severe/critical condition. Compared to mild/moderate patients, 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 than patients with normal levels. Severe/critical COVID-19 patients with pre-existing CAD (165/1,515) 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 patients with elevated brain natriuretic peptide were at a higher risk of death. Conclusion and Implications: 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.