Assessing the Elevation of Cardiac Biomarkers and the Severity of COVID-19 Infection: A Meta-analysis

Abstract

- Purpose: Since December 2019, coronavirus disease 2019 infection has become a global pandemic. The cases of Coronavirus Disease 2019 (COVID-19)-related acute cardiac injury with unknown pathophysiologic mechanism has become increasingly prevalent. However, it is not yet understood how the extent of cardiac injury differs with the intensity of viral infection. In the current study, we aimed to assess the association between elevated cardiac biomarkers and the severity of COVID-19 infection. Methods: A systematic literature search was performed across PubMed and Embase databases from December 1, 2019 to July 10, 2020, to identify studies that reported cardiac biomarkers of troponin (TnI) and creatine kinase-myocardial band (CK-MB) in patients with COVID-19. These studies compared non-severe patients with severe patients, or survivors with non-survivors or medical patients with critically ill patients. The data were extracted for TnI, CK-MB, N-terminal-brain natriuretic peptide (NT-BNP), D-dimer, and lactate dehydrogenase (LDH), C-reactive protein (CRP), and interleukin 6 (IL-6). Wherever possible, the data were pooled for meta-analysis (Review Manager, RevMan. version 5.3) with standard or weighted mean or median difference and corresponding 95% confidence intervals (95% CI). Results: A total of 25 studies involving 5,626 patients were included in the present analysis. More severe COVID-19 infection was found to be associated with higher mean values of TnI (-0.54 [-0.72, -0.36]) (ng/mL), CK-MB (-1.55 [-2.23, -0.88]) (ng/mL) and (-4.75 [-13.31, 3.82]) (units/L), NT-BNP (-815.7 [-1073.97, -557.42]) (pg/mL), D-dimer (-1.4 [-2.04, -0.77]) (mcg/mL), and LDH (-176.59 [-224.11, -129.06]) (units/L), as well as CRP (-64.03 [-68.88, -59.19]) (mg/L) and IL-6 (-22.59 [-29.39, -15.79]) (pg/mL). Conclusions: There is significant association between elevated cardiac biomarkers and the severity of COVID-19, which underlines the increased risk of acute cardiac injury with more severe viral infection. This highlights the need to understand the cardiac history among the COVID-19 patients during initial assessment and for monitoring.

Serum CK-MB, COVID-19 severity and mortality: An updated systematic review and meta-analysis with meta-regression

“…Previous systematic reviews and meta-analyses have reported associations between serum CK-MB concentrations and COVID-19 severity and mortality [ [19] , [20] , [21] , [22] ]. Our meta-analysis has captured more than double the number of studies, 55 vs. 25, and participants, 11,791 vs. 5,626, than the largest previously published meta-analysis [ 21 ]. Furthermore, we investigated possible associations between the observed SMD and a number of biologically and clinically plausible factors.…”

“…A number of systematic reviews and meta-analyses on troponin and COVID-19 have been published [ [15] , [16] , [17] , [18] ]. Similarly, meta-analyses have sought to critically appraise the available evidence regarding the clinical role of CK-MB [ [19] , [20] , [21] , [22] ], with the largest meta-analysis identifying a total of 25 studies in 5,626 COVID-19 patients [ 21 ]. While CK-MB is less used in the diagnosis and the monitoring of myocardial necrosis in contemporary clinical practice since the advent of high-sensitivity troponin, additional retrospective and prospective studies have since been published on the associations between serum CK-MB concentrations, COVID-19 severity, and adverse outcomes.…”

Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies

“…The inflammatory response to COVID-19 leads to increased systemic inflammatory markers and potential abnormal function of vital organ systems, including pulmonary and cardiovascular. We have previously shown that there is significant association between elevated cardiac and inflammatory biomarkers and the severity of COVID-19 ( 22 ). To our knowledge, no meta-analysis has addressed the association between vitamin D levels with cardiac and inflammatory biomarkers.…”

Natriuretic Peptide Levels and Clinical Outcomes Among Patients Hospitalized With Coronavirus Disease 2019 Infection

“…Another study has shown prognostic utility of proBNP in a small cohort (102 patients) of severe COVID-19 patients ( 11 ). A meta-analysis on cardiac biomarkers also demonstrated that NT-proBNP was significantly higher in severely ill COVID-19 patients compared with nonsevere cases ( 8 ). Only a few observational studies have not shown B-type natriuretic peptide (BNP) as a marker of clinical significance; although, comparatively, these studies were smaller, relatively racially homogenous, had limited follow-up time, and had significantly fewer days of mechanical ventilation ( 9 , 10 ).…”