key: cord-279566-27wmd3g5 authors: Shi, Li; Wang, Ying; Liang, Xuan; Xiao, Wenwei; Duan, Guangcai; Yang, Haiyan; Wang, Yadong title: Is neutrophilia associated with mortality in COVID‐19 patients? A meta‐analysis and meta‐regression date: 2020-07-24 journal: Int J Lab Hematol DOI: 10.1111/ijlh.13298 sha: doc_id: 279566 cord_uid: 27wmd3g5 nan view, and studies with overlapping data were excluded. Considering the inherent differences among studies, we calculated the pooled standardized mean difference (SMD) and corresponding 95% confidence interval (CI) for continuous variables by using random-effects model to evaluate the relationship between changes in neutrophil counts and mortality of COVID-19 patients. When the mean and standard deviation could not be extracted directly from studies, we estimated them according to Wan et al's 9 method by utilizing sample size, median and interquartile range (IQR), or median and range. The I 2 statistic and Cochran's Q statistic were used to quantify the heterogeneity across studies. 10 For the Cochran's Q statistic, significant heterogeneity across studies was deemed as a P-value <.10. For the I 2 statistic, significant heterogeneity across studies was regarded as I 2 > 50%. In addition, we also provided the prediction interval, which was helpful for assessing whether the variation across studies was clinically significant. 11, 12 We used age and gender as covariates to conduct a restricted-maximum likelihood random-effects meta-regression. Sensitivity analysis was used not only to identify sources of heterogeneity but also to assess the robustness of the results. For assessing small-study effects, we chose Begg's test and regression-based Egger's test. All demonstrated no small-study effects for the relationship between neutrophil counts and increased risk of mortality in COVID-19 patients. Our current study demonstrated that the elevated neutrophil counts were significantly correlated to the mortality of COVID-19 patients. However, there was high heterogeneity in our study. To find sources of heterogeneity, we conducted a meta-regression. Considering the relationship between age and gender and mortality in COVID-19 patients, 18 we selected age and gender as covariables based on the available data provided by the included studies. Although meta-regression did not identify the sources of heterogeneity, sensitivity analysis indicated that our results were reliable and robust. Besides, the prediction interval showed that values were possible on both sides of the null (prediction interval = −0.12-1.99). Hence, interpretation of our results in some settings or different study populations should be taken with caution. There are still some other limitations to our meta-analysis. This meta-analysis was based on only 10 published studies with 1473 COVID-19 cases. Therefore, future studies with larger sample size are needed to support our results. Besides, most of the studies were from China and only one was from Spain, so the scope of our findings might be limited. In conclusion, neutrophilia is a risk factor for mortality of COVID-19 patients, and our results are required to be verified by a study analyzing the adjusted effect estimates in the future. Prognostic value of leukocytosis and lymphopenia for coronavirus disease severity Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China Survival study of hospitalized patients with concurrent Covid-19 and haematological malignancies Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement Systems to rate the strength of scientific evidence Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range Measuring inconsistency in meta-analyses Plea for routinely presenting prediction intervals in meta-analysis Basics of meta-analysis: I(2) is not an absolute measure of heterogeneity COVID-19 in persons with haematological cancers 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 Coronavirus disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up Clinical characteristics and outcomes of patients with severe covid-19 with diabetes Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies