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

Rahul Chaudhary; Jalaj Garg; Damon E Houghton; M Hassan Murad; Ashok Kondur; Rohit Chaudhary; Waldemar E Wysokinski; Robert D McBane 2nd

doi:10.1016/j.mayocpiqo.2021.01.009

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

Mayo Clin Proc Innov Qual Outcomes. 2021 Apr;5(2):388-402. doi: 10.1016/j.mayocpiqo.2021.01.009. Epub 2021 Feb 8.

Authors

Rahul Chaudhary^{1

2}, Jalaj Garg³, Damon E Houghton⁴, M Hassan Murad⁵, Ashok Kondur⁶, Rohit Chaudhary⁷, Waldemar E Wysokinski⁴, Robert D McBane 2nd⁴

Affiliations

¹ Division of Hospital Internal Medicine, Mayo Clinic, Rochester, MN.
² Division of Cardiology, University of Pittsburgh Medical Center Heart and Vascular Institute, Pittsburgh, PA.
³ Division of Cardiology, Medical College of Wisconsin, Milwaukee.
⁴ Division of Vascular Medicine, Mayo Clinic, Rochester, MN.
⁵ Evidence-based Practice Center, Mayo Clinic, Rochester, MN.
⁶ Division of Cardiology, Garden City Hospital, Garden City, MI.
⁷ Deakin University, Melbourne, Australia.

Abstract

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; I ² =83.85%), fibrinogen (WMD, 0.42; 95% CI, 0.18 to 0.67; I ² =61.88%; P<.001), C-reactive protein (CRP) (WMD, 35.74; 95% CI, 30.16 to 41.31; I ² =85.27%), high-sensitivity CRP (WMD, 62.68; 95% CI, 45.27 to 80.09; I ² =0%), interleukin 6 (WMD, 22.81; 95% CI, 17.90 to 27.72; I ² =90.42%), and ferritin (WMD, 506.15; 95% CI, 356.24 to 656.06; I ² =52.02%). Moderate to significant heterogeneity was observed for all parameters (I ² > 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.

Keywords: COVID-19, coronavirus disease 2019; CRP, C-reactive protein; ECMO, extracorporeal membrane oxygenation; IL-6, interleukin 6; LDH, lactate dehydrogenase; OR, odds ratio; WMD, weighted mean difference; hs, high-sensitivity.