Association of heme/hemopexin/heme-oxygenase 1 pathway with clinical and laboratory markers of severity in Covid-19

ABSTRACT

Background: Heme-oxygenase 1 (HO-1) is an intracellular enzyme that is part of a broad anti-inflammatory and antioxidative pathway, in which it metabolizes heme delivered to cells by hemopexin. Although initial suggestions of a direct action of SARS-CoV- 2 on hemoglobin or heme have already been refuted, HO-1 activation is recognized as part of the host response and as a potential therapeutic target in several diseases involving thrombosis and inflammation. Aim(s) To evaluate circulating levels of hemopexin, heme and HO-1 in COVID-19, and their association with clinical and laboratory markers of disease severity. Method(s) Thirty consecutive patients with confirmed COVID-19 admitted due to hypoxemia were enrolled, along with 30 age and sex-matched healthy volunteers. HO-1 and hemopexin were measured by ELISA, and heme was measured by a colorimetric method. Samples were obtained on admission. Coagulation and inflammatory biomarkers were measured using commercional kits. Result(s) HO-1 levels were higher in patients compared to healthy volunteers, and a trend towards higher hemopexin levels was also observed. In contrast heme levels were similar in patients and controls. A significant decrease in HO-1 levels was observed at the 4th day of hospital stay, and the magnitude of this decrease (DELTAHO-1) was correlated with the number of days in intensive care. Moreover, admission HO-1 levels were correlated with several biomarkers of hemostasis and fibrinolysis activation. Conclusion(s) Upregulation of HO-1 is observed in COVID-19. HO-1 levels on admission were associated with markers of coagulation and fibrinolysis activation. Persistance of high HO-1 levels during admssion was associated with longer ICU stay. (Figure Presented).