Association of heme-oxygenase 1, hemopexin, and heme levels with markers of disease severity in COVID-19

Author(s):Show less -

de Lima, Franciele ; Moraes, Carla Roberta Peachazepi ; Barbosa, Mayck Silva ; Bombassaro, Bruna ; Palma, Andre C. ; Dertkigil, Sergio San Juan ; Moretti, Maria Luiza ; Orsi, Fernanda Andrade ; Annichino-Bizzacchi, Joyce M. ; Mansour, Eli ; Velloso, Licio A. ; De Paula, Erich Vinicius

• Document type: Journal article
• Source: Experimental Biology and Medicine; v. N/A, p. 8-pg., 2023-02-05.

Abstract

Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 +/- 2696 vs 1953 +/- 612 pg/mL, respectively, P < 0.0001), as well as a trend toward increased levels of HPX (3.724 +/- 0.880 vs 3.254 +/- 1.022 mg/mL, respectively; P = 0.06). In addition, HO-1 and HPX levels reduced from admission to day + 4. HO-1 levels were associated with duration of intensive care unit stay and with several markers of coagulation activation. In conclusion, modulation of HO-1 could be associated with the prothrombotic state observed in COVID-19, and HO-1 could also represent a relevant biomarker for COVID-19. New independent studies are warranted to explore and expand these findings. (AU)

• FAPESP's process: 16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders
• Grantee: Joyce Maria Annichino-Bizzacchi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/05985-9 - Evaluation of the mechanisms of hemostatic activation in COVID-19 and their modulation by bradykinin inhibitors
• Grantee: Erich Vinicius de Paula
• Support Opportunities: Regular Research Grants