Abstract
Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02–0.25], p < 0.001) and thrombosis (OR 0.36 95%CI [0.14–0.82], p = 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19.
【초록키워드】 COVID-19, Inflammation, Mortality, thrombosis, severe COVID-19, Anti-inflammatory, Hospitalization, IL-6, cross-sectional, severity, variant, COVID-19 severity, Sex, Critically ill, pathophysiology, therapeutic, Patient, Logistic regression, plasma, age, BMI, Admission, patients, predict, mechanism, in-hospital mortality, Protective, marker, Anticoagulant, Predictive, intensity, D-dimer levels, 95%CI, tissue, multivariable analysis, protective factor, hallmark, offer, survivor, non-survivor, Occurrence, performed, examined, involved, proportion, adjusted, hospitalized patient, suffered, subset, phenotyped, Restoring, with COVID-19, 【제목키워드】 COVID-19, thrombosis, in-hospital mortality, alpha-1-antitrypsin, Imbalance,