Gamma' Fibrinogen Levels As a Biomarker of COVID-19 Severity

Introduction: COVID-19 is associated with maladaptive inflammation that can lead to acute respiratory distress syndrome. We therefore investigated a novel inflammatory marker, γ' fibrinogen, which is associated with cardiovascular diseases.

Hypothesis: We had previously discovered that COVID-19 patients have among the highest levels of γ' fibrinogen that have ever been reported. We therefore hypothesized that γ' fibrinogen levels would be associated with disease severity.

Methods: 103 patients with COVID-19 and 19 healthy control volunteers were identified by RT-PCR. We measured γ' fibrinogen in blood draws from the patients and the controls. SpO₂ levels were measured in patients at the time of the blood draw.

Results: We found significant associations between γ' fibrinogen levels and the severity of COVID-19. The mean level of γ' fibrinogen in the patients with COVID-19 was 69.8 mg/dL compared to 36.9 mg/dL in the controls, whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Using ROC curves, γ' fibrinogen differentiated between COVID-19 patients and controls very well (AUC 0.91, 95% CI: 0.85-0.98; Youden's index cutpoint 46.9 mg/dL, sensitivity 0.81, specificity 0.84), and all other biomarkers had lower AUC.In addition, γ' fibrinogen was significantly higher in patients with severe COVID-19 (SpO₂<=93%), compared to mild/moderate COVID-19 (SpO₂ >93%) (p = 0.012, AUC of 0.68, 95% CI 0.57-0.79; Youden's index cutpoint 65.2 mg/dL, sensitivity 0.63, specificity 0.70). In contrast, CRP, interleukin-6 (IL-6), ferritin, LDH, D-dimer, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Furthermore, γ' fibrinogen levels did not correlate significantly with IL-6, ferritin, D-dimer, or total fibrinogen. These findings suggest that the associations between COVID-19 and COVID-19 severity with γ' fibrinogen levels cannot be due simply to total fibrinogen levels.

Conclusions: Our results suggest that γ' fibrinogen is a robust inflammatory marker for COVID-19 that may be useful in predicting COVID-19 disease severity.

Kornblith:Gamma Diagnostics, Inc.: Consultancy. Noll:Gamma Diagnostics, Inc.: Ended employment in the past 24 months. Farrell:Gamma Diagnostics, Inc.: Consultancy, Current equity holder in private company, Other: Founder, Research Funding.