ABSTRACT
Introduction: COVID-19 p atients o ften d evelop s ystemic i nflammation and hypercoagulability, leading to an increased thromboembolism risk and a poor evolution. The D-dimer level at the time of hospitalization predicts the risk of acute respiratory distress syndrome development, intensive care admission and death. Identifying additional biomarkers to assist physicians in risk stratification and decision-making processes is of upmost importance. Growth arrest-specific gene 6 (GAS6) is a vitamin K-dependent protein that plays a role in thrombosis, hemostasis, and inflammation and is a ligand for tyrosine kinase receptors AXL, MERTK & TYRO3 (TAM). AXL h as b een suggested to be a novel host receptor that promotes SARS-CoV-2 entry into human cells (Cell Research 2021, 31:126-140). Our goal was to determine if GAS6 and TAM receptors plasma level may be used as biomarker of disease severity in patients with COVID-19 and to assess if there is a correlation between GAS6 and D-dimer levels. Method(s): We enrolled a prospective observational single-center s tudy i ncluding 1 10 a dult p atients w ith P CR-confirmed SARS-CoV-2 infection from whom blood was collected at prespecified time points. Plasma concentrations of GAS6 and TAM receptors were determined by ELISA. Furthermore, coagulation parameters were measured in plasma. Result(s): The patient cohort was scored using the WHO Ordinal Scale for Clinical Improvement 2020 and divided into "mild COVID-19" (<=4) and "severe COVID-19" (>=5). Our data showed that plasma Gas6 level significantly increases with the severity of the COVID-19 disease (mild COVID-19: 10.72 +/- 1.33 ng/ml vs severe COVID-19: 18.70 +/- 1.05 ng/ml). Furthermore, we detected a significant increase in sAXL (mild COVID-19: 17.80 +/- 1.85 n g/ml v s s evere C OVID-19: 26.14 +/- 3.81 ng/ml) and sMERTK (mild COVID-19: 6.42 +/- 0.8 ng/ml vs severe COVID-19: 8.55 +/- 0.53 ng/ml) as well as an increase of sTyro3 by trend (mild COVID-19: 1.55 +/- 0.25 ng/ml vs severe COVID-19: 2.13 +/- 0.35 ng/ml) (Figure 1B). There was a positive correlation between increasing Gas6 levels and higher sAXL and sTYRO3 levels (Figure 1B). The WHO Ordinal Scale for Clinical Improvement 2020 positive correlated with sMERTK and D-Dimer levels. Conclusion(s): Gas6, sAXL, sMERTK, sTYRO3 might constitute valid biomarkers to help the clinician to tailor therapy in the assessment of COVID-19 severity in individual patients. (Figure Presented).
ABSTRACT
Background and aims: Cerebral venous sinus thrombosis with thrombocytopenia syndrome (CVST-TTS) is a rare adverse effect of adenovirus- based SARS-CoV-2 vaccines. After the autoimmune pathogenesis of TTS was discovered, treatment recommendations were issued. The aim of this study was to evaluate if adherence to treatment recommendations was associated with lower mortality. Methods: TTS was defined according to the Brighton criteria. Cases from a prospective international CVT registry with symptom onset within 28 days of adenovirus-based SARS-CoV-2 vaccination were analysed. Treatment recommendations, following the International Society of Thrombosis and Haemostasis, included use of immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusions, unless needed for surgery. Results: Out of 178 CVT cases from 117 centres in 19 countries reported between March 29 and September 3, 2021, 95 patients fulfilled inclusion criteria. Five of 37 (14%), 13/25 (52%), and 29/33 (88%) of patients diagnosed in March, April, and from May onwards, respectively, were treated according to recommendations. Proportion of patients diagnosed in March, April, and from May onwards who received immunomodulation increased from 19/37 (51%) over 15/25 (60%) to 30/33 (90%), and the percentage of patients who were treated with heparins [26/37 (70%), 4/25 (16%), 1/33 (3%)] and platelet transfusion [15/37 (41%), 4/25 (16%), 7/33 (21%), respectively] decreased accordingly. Mortality of patients treated according to recommendations was 14/47 (30%, 95%CI 19-44%) compared to 28/48 (58%, 95%CI 44-71%) in patients not treated according to recommendations (OR 3.30, 95%CI 1.41-7.71). Conclusions: Over time, adherence to treatment recommendations improved, and mortality rate of patients with CVST-TTS decreased.