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Serum CK-MB, COVID-19 severity and mortality: An updated systematic review and meta-analysis with meta-regression
Angelo Zinellu1, Salvatore Sotgia1, Alessandro G Fois2
1Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Insights
Elevated creatine kinase-MB (CK-MB) levels in COVID-19 patients indicate severe disease and higher mortality risk. This myocardial injury biomarker aids in risk stratification for infected individuals.
Area of Science:
- Cardiology
- Infectious Diseases
- Biomarker Research
Background:
- COVID-19 can cause myocardial injury, impacting patient outcomes.
- Creatine kinase-MB (CK-MB) is a known biomarker for heart muscle damage.
Purpose of the Study:
- To systematically review and meta-analyze the association between CK-MB levels and COVID-19 severity and mortality.
- To explore potential predictors of elevated CK-MB in COVID-19 patients through meta-regression.
Main Methods:
- A systematic search of PubMed, Web of Science, and Scopus for studies published between January 2020 and January 2021.
- Meta-analysis and meta-regression of data from 55 studies involving 11,791 COVID-19 patients.
- Assessment of CK-MB concentrations, disease severity, and mortality, including sensitivity analyses and publication bias tests.
Main Results:
- Significantly higher CK-MB concentrations were observed in severe COVID-19 cases and non-survivors compared to mild cases and survivors (SMD 0.81).
- The proportion of patients with elevated CK-MB was substantially higher in severe/non-survivor groups (RR 2.84).
- Meta-regression revealed positive associations between CK-MB and white blood cell count, AST, myoglobin, troponin, BNP, LDH, and D-dimer.
Conclusions:
- Elevated CK-MB levels are significantly associated with increased COVID-19 severity and mortality.
- CK-MB may serve as a valuable biomarker for risk stratification in COVID-19 patients.
- Further research may elucidate the precise role of myocardial injury in COVID-19 pathogenesis.
Objectives:
We conducted a systematic review and meta-analysis with meta-regression of creatine kinase-MB (CK-MB), a biomarker of myocardial injury, in COVID-19 patients.
Methods:
We searched PubMed, Web of Science and Scopus, for studies published between January 2020 and January 2021 that reported CK-MB, COVID-19 severity and mortality (PROSPERO registration number: CRD42021239657).
Results:
Fifty-five studies in 11,791 COVID-19 patients were included in the meta-analysis. The pooled results showed that CK-MB concentrations were significantly higher in patients with high disease severity or non-survivor status than patients with low severity or survivor status (standardized mean difference, SMD, 0.81, 95% CI 0.61 to 1.01, p<0.001). The rate of patients with CK-MB values above the normal range was also significantly higher in the former than the latter (60/350 vs 98/1,780; RR = 2.84, 95%CI 1.89 to 4.27, p<0.001; I2 = 19.9, p = 0.254). Extreme between-study heterogeneity was observed (I2 = 93.4%, p<0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified (effect size range, 0.77 to 0.84). Begg's (p = 0.50) and Egger's (p = 0.86) t-tests did not show publication bias. In meta-regression analysis, the SMD was significantly and positively associated with the white blood count, aspartate aminotransferase, myoglobin, troponin, brain natriuretic peptide, lactate dehydrogenase, and D-dimer.
Conclusions:
Higher CK-MB concentrations were significantly associated with severe disease and mortality in COVID-19 patients. This biomarker of myocardial injury might be useful for risk stratification in this group.
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