A meta-analysis of potential biomarkers associated with severity of coronavirus disease 2019 (COVID-19)

Abstract

Abstract Background Prognostic factors for the Coronavirus disease 2019 (COVID1–9) are not well established. This study aimed to summarize the available data on the association between the severity of COVID-19 and common hematological, inflammatory and biochemical parameters. Methods EMBASE, MEDLINE, Web of sciences were searched to identify all published studies providing relevant data. Random-effects meta-analysis was used to pool effect sizes. Results The bibliographic search yielded 287 citations, 31 of which were finally retained. Meta-analysis of standardized mean difference (SMD) between severe and non-severe COVID-19 cases showed that CK-MB (SMD = 0.68,95%CI: 0.48;0.87; P-value:< 0.001), troponin I (SMD = 0.71, 95%CI:0.42;1.00; P-value:< 0.001), D-dimer (SMD = 0.54,95%CI:0.31;0.77; P-value:< 0.001), prothrombin time (SMD = 0.48, 95%CI:0.23;0.73; P-value: < 0.001), procalcitonin (SMD = 0.72, 95%CI: 0.34;1,11; P-value:< 0.001), interleukin-6 (SMD = 0.93, 95%CI: 0.25;1.61;P-value: 0.007),C-reactive protein (CRP) (SMD = 1.34, 95%CI:0.83;1.86; P-value:< 0.001), ALAT (SMD = 0.53, 95%CI: 0.34;0,71; P-value:< 0.001), ASAT (SMD = 0.96, 95%CI: 0.58;1.34; P-value: < 0.001), LDH (SMD = 1.36, 95%CI: 0.75;1.98; P-value:< 0.001), CK (SMD = 0.48, 95%CI: 0.10;0.87; P-value:0.01), total bilirubin (SMD = 0.32, 95%CI: 0.18;0.47;P-value: < 0.001), γ-GT (SMD = 1.03, 95%CI: 0.83;1.22; P-value: < 0.001), myoglobin (SMD = 1.14, 95%CI: 0.81;1.47; P-value:< 0.001), blood urea nitrogen (SMD = 0.32, 95%CI: 0.18;0.47;P-value:< 0.001) and Creatininemia (SMD = 0.18, 95%CI: 0.01;0.35; P-value:0.04) were significantly more elevated in severe cases, in opposition to lymphocyte count (SMD = -0.57, 95%CI:-0.71; − 0.42; P-value: < 0.001) and proportion of lymphocytes (SMD = -0.81, 95%CI: − 1.12; − 0.49; P-value:< 0.001) which were found to be significantly lower in severe patients with other biomarker such as thrombocytes (SMD = -0.26, 95%CI: − 0.48; − 0.04; P-value:0.02), eosinophils (SMD = − 0.28, 95%CI:-0.50; − 0.06; P-value:0.01), haemoglobin (SMD = -0.20, 95%CI: − 0.37,-0.03; P-value:0.02), albuminemia (SMD-1.67,95%CI -2.40; − 0.94; P-value:< 0.001), which were also lower. Furthermore, severe COVID-19 cases had a higher risk to have lymphopenia (RR =1.66, 95%CI: 1.26;2.20; P-value:0.002), thrombocytopenia (RR = 1.86, 95%CI: 1.59;2.17; P-value: < 0.001), elevated procalcitonin level (RR = 2.94, 95%CI: 2.09–4.15; P-value:< 0.001), CRP (RR =1.41,95%CI: 1.17–1.70; P-value:0.003), ASAT(RR =2.27, 95%CI: 1.76;2.94; P-value:< 0.001), CK(RR = 2.61, 95%CI: 1.35;5.05; P-value: 0.01), Creatininemia (RR = 3.66, 95%CI: 1.53;8.81; P-value: 0.02) and LDH blood level (RR = 2.03, 95%CI: 1.42;290; P-value: 0.003). Conclusion Some inflammatory (procalcitonin, CRP), haematologic (lymphocyte, Thrombocytes), and biochemical (CK-MB, Troponin I, D-dimer, ASAT, ALAT, LDH, γ-GT) biomarkers are significantly associated with severe COVID-19. These biomarkers might help in prognostic risk stratification of patients with COVID-19.