Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients

Objective: To evaluate differences in thromboinflammatory biomarkers between patients with severe coronavirus disease 2019 (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 thromboinflammatory biomarkers in COVID-19 among patients with severe COVID-19 disease or death (severe/nonsurvivors) and those with nonsevere disease or survivors (nonsevere/survivors) from January 1, 2020, through July 11, 2020. Inclusion criteria were (1) hospitalized patients 18 years or older comparing severe/nonsurvivors vs nonsevere/survivors and (2) biomarkers of inflammation and/or thrombosis. A random-effects model was used to estimate the weighted mean difference (WMD) between the 2 groups of COVID-19 severity. Results: We included 75 studies with 17,052 patients. The severe/nonsurvivor group was older, had a greater proportion of men, and had a higher prevalence of hypertension, diabetes, cardiac or cerebrovascular disease, chronic kidney disease, malignancy, and chronic obstructive pulmonary disease. Thromboinflammatory biomarkers were significantly higher in patients with severe disease, including D-dimer (WMD, 0.60; 95% CI, 0.49 to 0.71; I2=83.85%), fibrinogen (WMD, 0.42; 95% CI, 0.18 to 0.67; I2=61.88%; P 25%). Subanalysis based on disease severity, mortality, and geographic region of the studies revealed similar inferences. Conclusion: Thromboinflammatory biomarkers (D-dimer, fibrinogen, CRP, high-sensitivity CRP, ferritin, and interleukin 6) and marker of end-organ damage (high-sensitivity troponin I) are associated with increased severity and mortality in COVID-19 infection.