Cardiac Injury Biomarkers and the Risk of Death in Patients with COVID-19: A Systematic Review and Meta-Analysis

BACKGROUND: Cardiac complications may develop in a proportion of patients with the novel coronavirus disease (COVID-19), which may influence their prognosis. OBJECTIVES: To assess the role of cardiac injury biomarkers measured on admission and during hospitalization as risk factors for subsequent death in COVID-19 patients. METHODS: A systematic review and meta-analysis was carried out involving cohort studies that compared the levels of cardiac injury biomarkers in surviving and dead COVID-19 patients. Cardiac injury is defined as an elevation of the definitive markers (cardiac troponin (cTnI and cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)) above the 99th percentile upper reference limit. Secondary markers included creatine kinase-myocardial bound (CK-MB), myoglobin, interleukin-6 (IL-6), and C-reactive protein (CRP). The risk of death and the differences in marker concentrations were analyzed using risk ratios (RRs) and standardized mean differences (SMDs), respectively. RESULTS: Nine studies met the inclusion criteria (1799 patients, 53.36% males, 20.62% with cardiac injury). The risk of death was significantly higher in patients with elevated cTn than those with normal biomarker levels (RR = 5.28, P < 0.0001). Compared to survivors, dead patients had higher levels of cTn (SMD = 2.15, P=0.001), IL-6 (SMD = 3.13, P=0.03), hs-CRP (SMD = 2.78, P < 0.0001), and CK-MB (SMD = 0.97, P < 0.0001) on admission and a significant rise of plasma cTnT during hospitalization. CONCLUSION: COVID-19 patients with elevated cTn on admission, possibly due to immune-mediated myocardial injury, are at increased risk for mortality. This requires further radiographic investigations, close monitoring, and aggressive care to reduce the risk of severe complications and death.