Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: a meta-analysis and systematic review

Abstract

Background: Cardiac injury is now a common complication of coronavirus disease (COVID-19), but it remains unclear whether cardiac injury-related biomarkers can be independent predictors of mortality and severe disease development or intensive care unit (ICU) admission.

Methods: Two investigators searched the PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), Wanfang, MedRxiv, and ChinaXiv databases for articles published through March 30, 2020. Retrospective studies assessing the relationship between the prognosis of COVID-19 patients and levels of troponin I (TnI) and other cardiac injury biomarkers (creatine kinase [CK], CK myocardial band [CK-MB], lactate dehydrogenase [LDH], and interleukin-6 [IL-6]) were included. The data were extracted independently by two investigators.

Results: The analysis included 23 studies with 4631 total individuals. The proportions of severe disease, ICU admission, or death among patients with non-elevated TnI (or troponin T [TnT]), and those with elevated TnI (or TnT) were 12.0% and 64.5%, 11.8% and 56.0%, and 8.2% and. 59.3%, respectively. Patients with elevated TnI levels had significantly higher risks of severe disease, ICU admission, and death (RR 5.57, 95% CI 3.04 to 10.22, P < 0.001; RR 6.20, 95% CI 2.52 to 15.29, P < 0.001; RR 5.64, 95% CI 2.69 to 11.83, P < 0.001). Patients with an elevated CK level were at significantly increased risk of severe disease or ICU admission (RR 1.98, 95% CI 1.50 to 2.61, P < 0.001). Patients with elevated CK-MB levels were at a higher risk of developing severe disease or requiring ICU admission (RR 3.24, 95% CI 1.66 to 6.34, P = 0.001). Patients with newly occurring arrhythmias were at higher risk of developing severe disease or requiring ICU admission (RR 13.09, 95% CI 7.00 to 24.47, P < 0.001). An elevated IL-6 level was associated with a higher risk of developing severe disease, requiring ICU admission, or death.

Conclusions: COVID-19 patients with elevated TnI levels are at significantly higher risk of severe disease, ICU admission, and death. Elevated CK, CK-MB, LDH, and IL-6 levels and emerging arrhythmia are associated with the development of severe disease and need for ICU admission, and the mortality is significantly higher in patients with elevated LDH and IL-6 levels.

Keywords: Biomarkers; COVID-19; Cardiac injury; Meta-analysis; Mortality.

Fig. 1

Flow diagram showing study search and selection. CNKI=Chinese National Knowledge Infrastructure

Fig. 2

Forest plots comparing of risk of severe disease (a), ICU admission (b), and death (c), and the N-terminal pro-BNP levels (d) in patients with or without elevated troponin I (or troponin T). ICU, intensive care unit; BNP, B-type natriuretic peptide; RR, risk ratios; SMD, standard mean

Fig. 3

Forest plots comparing of the proportion of patients with elevated troponin I or troponin T levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (a), the troponin I levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (b), and the proportion of patients with elevated troponin I or troponin T levels in the survivors and non-survivors groups (c). ICU, intensive care unit; RR, risk ratios; SMD, standard mean

Fig. 4

Forest plots comparing of the proportion of patients with elevated creatinine kinase levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (a), the creatinine kinase levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (b), and the proportion of patients with elevated creatinine kinase–myocardial band levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (c). ICU, intensive care unit; RR, risk ratios; SMD, standard mean

Fig. 5

Forest plots comparing of the proportion of patients with elevated lactate dehydrogenase levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (a), the lactate dehydrogenase levels in the severe disease/ICU group and in the non-severe disease/non-ICU group (b), and the lactate dehydrogenase levels in the survivors and non-survivor groups (c). ICU, intensive care unit; RR, risk ratios; SMD, standard mean

Fig. 6

Forest plots comparing of the risk of developing to severe disease or requiring ICU admission among patients with or without newly occurring arrhythmias (a), the interleukin-6 levels in the severe disease/ICU group (b), and in the non-severe disease/non-ICU group and the interleukin-6 levels in the survivors and non-survivors groups (c). ICU, intensive care unit; RR, risk ratios; SMD, standard mean