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.

Myocardial Injury Is Associated with Higher Morbidity and Mortality in Patients with 2019 Novel Coronavirus Disease (COVID-19)

“…Among 143 patients with COVID-19, 31 (21.7%) who had significantly higher mortality. In cardiac injury group, the median duration from illness onset to death was 17.8 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] days; a figure that is comparable to published data in literature. Shi et al [14] described in a retrospective cohort of patients with COVID-19 that 19.7% had cardiac injury with mortality rate of 51.2% compared with 4.5% in non-cardiac injury group.…”

“…Cardiac injury is a common condition among COVID-19 hospitalized patients [6] and is associated with an increased risk of in-hospital mortality [7]. A recently published systemic review [8] looked at more than 10 studies from Italy, USA, and China, has highlighted that myocardial injury is not uncommon in setting of COVID-19, and can lead to higher mortality in hospitalized patients.…”

“…The exact pathophysiological mechanisms that lead to myocardial injury caused by COVID-19 are not well understood [6]. The postulated mechanisms include direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response and exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia [6,7]. Cardiac Injury may manifest as severe myocarditis with reduced systolic function, and elevated troponin hs-TNI [10,11].…”

Arrhythmia in COVID-19

“…It has been reported that patients with elevated troponin I levels are at higher risk of severe disease, ICU admission, and death. Furthermore, new-onset arrhythmia, elevated biomarkers including creatinine kinase, creatinine kinase-MB, lactate dehydrogenase (LDH), inflammatory biomarkers including Creactive protein (CRP), and interleukin-6 levels are associated with severe disease [37,39]. Moreover, atrial arrhythmias were more common among COVID-19 patients requiring mechanical ventilation [24].…”

Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States

“…[35][36][37] Increases in a variety of inflammatory pathways, including bradykinin, interleukin-6, C-reactive protein, and growth differentiation factor 15, have been described in COVID-19. 8,9,[38][39][40][41][42][43][44][45][46][47] Further, heparin has been shown to block SARS-CoV-2 viral spike protein binding in experimental studies. [48][49][50] We postulate that the combination of heparin's known antithrombotic and anti-inflammatory effects, 6,7 in addition to viral infectivity attenuation may, at least in part, explain the observed benefit associated with prophylactic anticoagulation.…”