IL-6 and D-Dimer at Admission Predicts Cardiac Injury and Early Mortality during SARS-CoV-2 Infection

BACKGROUNDWe recently described mortality of cardiac injury in COVID-19 patients. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiacinjury and mortality patterns in COVID-19 is unknown. METHODSThis retrospective cohort study included 170 COVID-19 patients with cardiac injury at admission to Tongji Hospital in Wuhan from January 29-March 8, 2020. Temporal evolution of inflammatory cytokines, coagulation markers, clinical, treatment and mortality were analyzed. RESULTSOf 170 patients, 60 (35.3%) died early (<21d) and 61 (35.9%) died after prolonged stay. Admission lab work that correlated with early death were elevate levels of interleukin 6 (IL-6) (p<0.0001), Tumor Necrosis Factor-a (TNF-a) (p=0.0025), and C-reactive protein (CRP) (p<0.0001). We observed the trajectory of biomarker changes after admission, and determined that early mortality had a rapidly increasing D-dimer, gradually decreasing platelet and lymphocyte counts. Multivariate and simple linear regression models showed that death risk was determined by immune and thrombotic pathway activation. Increasing cTnI levels were associated with those of increasing IL-6 (p=0.03) and D-dimer (p=0.0021). Exploratory analyses suggested that patients that received heparin has lower early mortality compared to those who did not (p =0.07), despite similar risk profile. CONCLUSIONSIn COVID-19 patients with cardiac injury, admission IL-6 and D-dimer predicted subsequent elevation of cTnI and early death, highlighting the need for early inflammatory cytokine-based risk stratification in patients with cardiac injury. Condensed AbstractCOVID-19 with cardiac injury is associated with worse survival. Admission activation of immune, thrombotic biomarkers and their ability to predict cardiac injury and mortality patterns in COVID-19 is unknown. This study proved that cardiac injury in these patients is closely related to the activation of immunological and thrombotic pathways and can be predicted by admission biomarkers of these pathways. This study supports the strategy of biomarker-guided, point-of-care therapy that warrants further studies in a randomized manner to develop anti-immune and anti-thrombotic treatment regimens in severe COVID-19 patients with cardiac injury.