ABSTRACT
The coronavirus disease of 2019 (COVID-19) has altered medical practice around the globe and revealed critical deficiencies in hospital supply chains ranging from adequate personal protective equipment to life-sustaining ventilators for critically ill hospitalized patients. We developed the CRISIS ventilator, a gas-powered resuscitator that functions without electricity, and which can be manufactured using hobby-level three-dimensional (3D) printers and standard off-the-shelf equipment available at the local hardware store. CRISIS ventilators were printed and used to ventilate sedated female Yorkshire pigs over 24-h. Pulmonary and hemodynamic values were recorded throughout the 24-h run, and serial arterial blood samples were obtained to assess ventilation and oxygenation. Lung tissue was obtained from each pig to evaluate for signs of inflammatory stress. All five female Yorkshire pigs survived the 24-h study period without suffering from hypoxemia, hypercarbia, or severe hypotension requiring intervention. One animal required rescue at the beginning of the experiment with a traditional ventilator due to leakage around a defective tracheostomy balloon. The wet/dry ratio was 6.74 +/- 0.19 compared to historical controls of 7.1 +/- 4.2 (not significantly different). This proof-of-concept study demonstrates that our 3D-printed CRISIS ventilator can ventilate and oxygenate a porcine model over the course of 24-h with stable pulmonary and hemodynamic function with similar levels of ventilation-related inflammation when compared with a previous control porcine model. Our work suggests that virtual stockpiling with just-in-time 3D-printed equipment, like the CRISIS ventilator, can temporize shortages of critical infrastructure needed to sustain life for hospitalized patients.
ABSTRACT
Introduction: COVID-19 disease 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 disease 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. 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. Hypothesis: Our hypothesis was that γ' Fbg levels would be elevated in COVID-19 patients compared to historical controls, and that the degree of elevation would be associated with disease severity. 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 the GammaCoeur ELISA (Gamma Diagnostics, Patent Pending). Results: Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of γ' Fbg ever recorded. The previous highest γ' Fbg level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. γ' Fbg levels were significantly associated with the need for ECMO and mortality. Conclusions: We found that COVID-19 patients can develop extraordinarily high levels of γ' Fbg. This has 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 clinical 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.