Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients

Abstract

Objective: Evidence-based characterization of the diagnostic and prognostic value of the hematological and immunological markers related to the epidemic of Coronavirus Disease 2019 (COVID-19) is critical to understand the clinical course of the infection and to assess in development and validation of biomarkers.

Methods: Based on systematic search in Web of Science, PubMed, Scopus, and Science Direct up to April 22, 2020, a total of 52 eligible articles with 6,320 laboratory-confirmed COVID-19 cohorts were included. Pairwise comparison between severe versus mild disease, Intensive Care Unit (ICU) versus general ward admission and expired versus survivors were performed for 36 laboratory parameters. The pooled standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using the DerSimonian Laird method/random effects model and converted to the Odds ratio (OR). The decision tree algorithm was employed to identify the key risk factor(s) attributed to severe COVID-19 disease.

Results: Cohorts with elevated levels of white blood cells (WBCs) (OR = 1.75), neutrophil count (OR = 2.62), D-dimer (OR = 3.97), prolonged prothrombin time (PT) (OR = 1.82), fibrinogen (OR = 3.14), erythrocyte sedimentation rate (OR = 1.60), procalcitonin (OR = 4.76), IL-6 (OR = 2.10), and IL-10 (OR = 4.93) had higher odds of progression to severe phenotype. Decision tree model (sensitivity = 100%, specificity = 81%) showed the high performance of neutrophil count at a cut-off value of more than 3.74x109/L for identifying patients at high risk of severe COVID-19. Likewise, ICU admission was associated with higher levels of WBCs (OR = 5.21), neutrophils (OR = 6.25), D-dimer (OR = 4.19), and prolonged PT (OR = 2.18). Patients with high IL-6 (OR = 13.87), CRP (OR = 7.09), D-dimer (OR = 6.36), and neutrophils (OR = 6.25) had the highest likelihood of mortality.

Conclusions: Several hematological and immunological markers, in particular neutrophilic count, could be helpful to be included within the routine panel for COVID-19 infection evaluation to ensure risk stratification and effective management.

Fig 1. Literature search process.

(A) Workflow for screening and selecting relevant articles. (B) Map showing the location of the studies. Studies conducted in China (red), Taiwan (green), Singapore (blue), and USA (light blue) are shown with the number of studies between brackets. Data source Tableau 2020.1 Desktop Professional Edition (https://www.tableau.com/).

Fig 2. Trial sequential analysis.

Trial sequential analysis (TSA) for the neutrophil count. The acquired sample size of the neutrophil count was 1558 subjects and the cumulative Z-curve crossed the monitoring boundary before reaching the required sample size (n = 540), suggesting that the cumulative proof was reliable, and no additional trials are required to achieve the significance.