key: cord-0917816-nl3f4sqk authors: Shi, Li; Wang, Ying; Wang, Yadong; Duan, Guangcai; Yang, Haiyan title: Meta-analysis of Relation of Creatine kinase-MB to Risk of Mortality in Coronavirus Disease 2019 Patients date: 2020-06-10 journal: Am J Cardiol DOI: 10.1016/j.amjcard.2020.06.004 sha: db4b207c6719b22001686d3aa96195957ed501b2 doc_id: 917816 cord_uid: nl3f4sqk Recently, several emerging papers have focused on the association of the creatine kinase-MB (CK-MB) levels with the risk of mortality in infected coronavirus disease 2019 (COVID-19) patients. However, the conclusions are inconsistent. In order to obtain a definitive conclusion on the association between the levels of CK-MB and the risk of mortality in COVID-19 patients, a quantitative meta-analysis was conducted on the basis of published data. Chinese National Knowledge Infrastructure, Web of Science and PubMed databases were extensively searched. Five studies performed in China were finally included in this meta-analysis. The overall results showed that higher levels of CK-MB were significantly associated with an increased risk of the mortality in COVID-19 infected patients (SMD 0.99; 95% CI 0.57 to 1.42; P < 0.001). In conclusion, the elevated CK-MB levels were a crucial characteristic of the mortality of COVID-19 patients. infected patients. However, the conclusions drawn from different studies are inconsistent. [2] [3] [4] In order to obtain a definitive conclusion on the association between the levels of CK-MB and the risk of mortality in COVID-19 patients, a quantitative meta-analysis was conducted on the basis of published data. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was strictly enforced throughout the design and implementation of this meta-analysis. 5 Chinese National Knowledge Infrastructure, Web of Science and PubMed databases were extensively searched by two of the authors (Li Shi and Ying Wang) prior to May 5, 2020 with the following keywords: "characteristics", "clinical", "laboratory", "SARS-CoV-2", "2019-nCoV", "COVID-19", "coronavirus 2019", "outcome", "death" and "mortality". The mean and standard deviation (SD) could be estimated by sample size, median and interquartile range (IQR) according to Wan et al's paper. 6 The screening criterion was that studies provided mean (SD) or median (IQR) for levels of CK-MB in both non-survival and survival COVID-19 infected patients. The pooled standardized mean difference (SMD) and 95% confidence interval (CI) were used to assess the effect sizes, since the units of CK-MB are different among the eligible studies. 7 We chose different models based on the incongruity index (I 2 ) (I 2 < 50% for the fixed-effects model; I 2 ≥ 50% for the 4 random-effects model). 8 In addition, sensitivity analysis was performed by sequentially omitting single study to test the stability of our final results. 9 The potential presence of publication bias was examined by Begg's regression test and Egger's linear regression test. 10, 11 All statistical analyses were conducted by using the Table 1 . Due to the high heterogeneity (I 2 = 86%, P < 0.001), we chose a random-effects model to conduct this synthetic analysis. The overall results showed that the elevated levels of CK-MB were significantly associated with an increased risk of the mortality in COVID-19 infected patients (SMD 0.99; 95% CI 0.57 to 1.42; P < 0.001) ( Figure 1A ). As indicated in Figure 1B , no single study was found to have obvious effects on the overall results, which suggests the stability of our results. As for the publication bias, both Begg's test (P = 0.806) and Egger's test (P = 0.642) ( Figure 1C ) exhibited that there was no publication bias in our present meta-analysis. Patients with severe pneumonia have varying degrees of myocardial injury due to hypoxemia and toxicity of the pathogen. [14] [15] [16] So do patients with COVID-19. 1,17,18 5 CK-MB mainly exists in the outer plasma layer of myocardial cells, and is the most specific enzyme in the myocardial enzyme spectrum for clinical diagnosis of myocardial injury. 19, 20 A previous meta-analysis by Li et al observed that the elevated CK-MB levels were associated with the severity of COVID-19 patients. 1 Our present meta-analysis suggests that the elevated levels of CK-MB were significantly associated with an increased risk of the mortality in COVID-19 infected patients. The impact of 2019 novel coronavirus on heart injury: A Systematic review and Meta-analysis Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan Clinical and laboratory predictors of in-hospital mortality in patients with COVID-19: a cohort study in Wuhan, China Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range Chapter 10: Analysing data and undertaking meta-analyses Cochrane Handbook for Systematic Reviews of Interventions Meta-analysis in clinical trials revisited Dyspnea rather than fever is a risk factor for predicting 7 mortality in patients with COVID-19 Operating characteristics of a rank correlation test for publication bias Bias in meta-analysis detected by a simple, graphical test Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19 Right Heart Function in Community-Acquired Pneumonia Acute myocarditis associated with novel Middle east respiratory syndrome coronavirus SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS Myocardial injury and COVID-19: Possible mechanisms Cardiovascular implications of the COVID-19 pandemic: a global perspective Cardiac markers used in the detection of myocardial injury Myocardial injury following myocardial revascularization. Detection by isoenzyme analysis