Thrombo-inflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 patients

Chaudhary, Rahul; Garg, Jalaj; Houghton, Damon E.; Murad, M. Hassan; Kondur, Ashok; Chaudhary, Rohit; Wysokinski, Waldemar E.; McBane, Robert D.

Objective To evaluate differences in thrombo-inflammatory biomarkers between patients with severe COVID-19 infection/death and mild infection. Patients and Methods Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for studies comparing thrombo-inflammatory biomarkers in COVID-19 among severe/non-survivors and non-severe/survivors from January 1, 2020 through July 11, 2020. Inclusion criteria: (1) hospitalized patients ≥18 years comparing severe/non-survivors vs. non-severe/survivors; (2) biomarkers of inflammation and/or thrombosis. A random-effects model was used to estimate the weighted mean difference (WMD) between the two groups of COVID-19 severity. Results Seventy-five studies were included (17,052 patients). Patients with severe COVID-19/non-survivors were older, a greater proportion were men, had a higher prevalence of hypertension, diabetes, cardiac or cerebrovascular disease, chronic kidney disease, malignancy, and COPD. The thrombo-inflammatory biomarkers were significantly higher in patients with severe disease including D-dimer (WMD 0.60, 0.49-0.71, I2=83.85%), fibrinogen (WMD 0.42, 0.18-0.67, I2=61.88%, p<0.001), CRP (WMD 35.74, 30.16-41.31, I2=85.27%), high sensitivity-CRP (WMD 62.68, 45.27-80.09, I2=0%), Interleukin-6 (WMD 22.81, 17.90-27.72, I2=90.42%) and, ferritin (WMD 506.15, 356.24-656.06, I2=52.02%). Moderate to significant heterogeneity was observed for all parameters. Sub-analysis based on disease severity, mortality, and geographic region of studies demonstrated similar inferences. Conclusions Thrombo-inflammatory biomarkers (D-dimer, Fibrinogen, CRP, hs-CRP, ferritin, and IL-6) and marker of end-organ damage (hs-Troponin I) are associated with increased severity and mortality in COVID-19 infection.