Extreme γ’ fibrinogen levels in COVID-19 patients
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Abstract
Background
COVID-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 γ’ fibrinogen (γ’ 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 γ’ 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.
Methods
COVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. γ’ 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 γ’ Fbg. γ’ Fbg levels were significantly associated with the need for ECMO and with mortality.
Conclusions
We found that COVID-19 patients can develop extraordinarily high levels of γ’ Fbg. The previous highest γ’ 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. γ’ 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 γ’ Fbg therefore provide a reservoir of heparin-resistant clot-bound thrombin when the γ’ 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.
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SciScore for 10.1101/2022.01.20.22269321: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Patients who had at least two EDTA plasma draws were randomly selected from this time frame. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did …
SciScore for 10.1101/2022.01.20.22269321: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Patients who had at least two EDTA plasma draws were randomly selected from this time frame. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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