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

Abstract

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.

B-Type Natriuretic Peptide Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression

“…Following full-text revision of the remaining 57 articles, 13 were further excluded because they did not meet the inclusion criteria. Thus, 44 studies in 18,856 COVID-19 patients, 14,569 (53% males, mean age 48 years) with low severity or survivor status and 4,287 (59% males, mean age 61 years) with high severity or non-survivor status, were included in the final analysis ( Figure 1 and Table 1 ) ( 7 , 21 – 63 ). Thirty-two studies were conducted in Asia ( 7 , 22 , 24 , 26 , 27 , 29 , 31 – 33 , 35 , 38 – 46 , 48 , 50 , 51 , 53 – 55 , 57 – 63 ), eight in Europe ( 25 , 28 , 30 , 34 , 47 , 49 , 52 , 56 ), three in America ( 23 , 36 , 37 ), and one in Africa ( 21 ).…”

“…Thirty-two studies were conducted in Asia ( 7 , 22 , 24 , 26 , 27 , 29 , 31 – 33 , 35 , 38 – 46 , 48 , 50 , 51 , 53 – 55 , 57 – 63 ), eight in Europe ( 25 , 28 , 30 , 34 , 47 , 49 , 52 , 56 ), three in America ( 23 , 36 , 37 ), and one in Africa ( 21 ). Thirty-two studies were retrospective ( 7 , 21 – 23 , 27 , 29 , 31 – 39 , 41 – 45 , 48 , 50 , 51 , 53 , 55 , 57 – 63 ), eight prospective ( 24 , 30 , 46 , 47 , 49 , 52 , 54 , 56 ), whereas the remaining four did not report the study design ( 25 , 26 , 28 , 40 ). Clinical endpoints included disease severity based on current clinical guidelines in 15 studies ( 21 , 24 , 33 , 39 – 41 , 43 , 48 , 54 , 55 ,…”

“…Thirty-two studies were retrospective ( 7 , 21 – 23 , 27 , 29 , 31 – 39 , 41 – 45 , 48 , 50 , 51 , 53 , 55 , 57 – 63 ), eight prospective ( 24 , 30 , 46 , 47 , 49 , 52 , 54 , 56 ), whereas the remaining four did not report the study design ( 25 , 26 , 28 , 40 ). Clinical endpoints included disease severity based on current clinical guidelines in 15 studies ( 21 , 24 , 33 , 39 – 41 , 43 , 48 , 54 , 55 , 57 – 59 , 62 , 63 ), hospitalization in one ( 37 ), ICU transfer in three ( 32 , 44 , 49 ), or need for mechanical ventilation in one ( 23 ), and survival status in 24 studies ( 7 , 22 , 25 – 31 , 34 – 36 , 38 , 42 , 45 – 47 , 50 – 53 , 56 , 60 , 61 ). Sixteen studies reported plasma BNP concentrations ( 23 , 24 , 26 , 33 , 35 …”

“…Clinical endpoints included disease severity based on current clinical guidelines in 15 studies ( 21 , 24 , 33 , 39 – 41 , 43 , 48 , 54 , 55 , 57 – 59 , 62 , 63 ), hospitalization in one ( 37 ), ICU transfer in three ( 32 , 44 , 49 ), or need for mechanical ventilation in one ( 23 ), and survival status in 24 studies ( 7 , 22 , 25 – 31 , 34 – 36 , 38 , 42 , 45 – 47 , 50 – 53 , 56 , 60 , 61 ). Sixteen studies reported plasma BNP concentrations ( 23 , 24 , 26 , 33 , 35 – 37 , 45 , 48 , 50 , 51 , 54 , 56 – 58 , 62 ), whereas the remaining 28 reported plasma NT-proBNP concentrations ( 7 , 21 , 22 , 25 , 27 – 32 , 34 , 38 – 44 , 46 , 47 , 49 , 52 , 53 , 55 , 59 – 61 , 63 ). Only one study reported cumulative 7-day mean plasma NT-proBNP concentrations ( …”

Global burden of acute myocardial injury associated with COVID-19: A systematic review, meta-analysis, and meta-regression

“…Different works of the literature showed that there is a strong correlation between acute myocardial Injury and COVID-19 infection. New studies are being published from around the globe but the link between acute myocardial injury and COVID-19, the prevalence, reliability of diagnostic modalities, independent predictors, and clinical outcomes are still uncertain and a topic of debate [ 22 , 24 , 26 , [32] , [33] , [34] , [35] , 41 , 44 , 50 , 53 , [57] , [58] , [59] , 62 , 76 , [81] , [82] , [83] , [84] , [85] ].…”