Extreme γ' fibrinogen levels in COVID-19 patients

BackgroundCOVID-19 progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as thrombosis and acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 progression, but have far too much daily intra-individual variability to be useful in tracking the course of the disease. In contrast, we have shown that the inflammatory biomarker {gamma} fibrinogen ({gamma} Fbg) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. Objectives: The aims of the study were to measure {gamma} Fbg in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. MethodsCOVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. {gamma} Fbg was measured using a commercial ELISA. Results: Our results showed that nine out of the seventeen patients with COVID-19 had extremely high levels of {gamma} Fbg. {gamma} Fbg levels were significantly associated with the need for ECMO and with mortality. ConclusionsWe found that COVID-19 patients can develop extraordinarily high levels of {gamma} Fbg. The previous highest {gamma} Fbg level that we are aware of was 80.3 mg/dL found in a study of 10,601 participants in the ARIC study. These results have several important clinical implications. {gamma} Fbg contains a high affinity binding site for thrombin that binds to anion-binding exosite II on thrombin and protects it from inactivation by heparin. High levels of {gamma} Fbg therefore provide a reservoir of heparin-resistant clot-bound thrombin when the {gamma} Fbg is clotted. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients and suggest that heparin prophylaxis may be less effective than using other anticoagulants, particularly direct thrombin inhibitors.