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

Angelo Zinellu, Salvatore Sotgia, Alessandro G. Fois, Arduino A. Mangoni

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)304-314
Number of pages11
JournalAdvances in Medical Sciences
Issue number2
Publication statusPublished - Sep 2021


  • COVID-19
  • Creatine kinase-MB
  • Creatine kinase-MB values Above the normal range
  • Disease severity
  • Mortality


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