Heme/Hemeoxygenase-1 System Is a Potential Therapeutic Intervention for COVID-19 Patients with Severe Complications

Maiti, Biplab K.

doi:10.1021/acsptsci.0c00136

Cited by 10 publications

(7 citation statements)

References 12 publications

(44 reference statements)

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“…This results in low-level oxygenation, elevation of free iron and the down regulation of heme oxygenase-1 (HO-1) [ 31 ]. Based on this observation it is speculated that Hb, HO-1 and iron overload are possible targets for the treatment of COVID-19 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity

et al. 2022

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Background Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. Methods The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. Results Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019–30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081–5108.103)). Conclusions For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity

et al. 2022

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“…HO-1 and heme metabolites have strong antiviral properties (Singh et al, 2020).They also protect against damaging inflammation and coagulopathy (Nath et al, 2020; Dysregulated inflammation and coagulopathy are particularly insidious features of COVID-19 that cause widespread damage to multiple organ systems (Tay et al, 2020). Many have suggested that induction of the HO-1 system by various agents could be of great benefit to patients suffering from COVID-19, (Dattilo, 2020;Fakhouri et al, 2020;Hooper, 2020;Maiti, 2020;Rossi et al, 2020;Singh et al, 2020;Wagener et al, 2020) however this idea is yet to be validated by experimental evidence. Relevant models in which Hemin has been demonstrated as protective include; acute lung injury (X.…”

Section: Discussionmentioning

confidence: 99%

“…The potential of HO-1 centric therapeutics to combat severe COVID-19 has been noted by several groups, yet the role of HO-1 in SARS-CoV-2 infection remains unclear (Dattilo, 2020; Fakhouri et al, 2020; Hooper, 2020; Maiti, 2020; Rossi et al, 2020; Singh et al, 2020; Wagener et al, 2020). Here we present experimental evidence for the antiviral capabilities of the HO-1-inducing drug Hemin in a cell line model of SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Hemin shows antiviral activity in vitro, possibly through suppression of viral entry mediators

Ünal

Bitirim²,

Somers³

et al. 2022

Preprint

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Heme oxygenase-1 (HO-1) is a stress-induced enzyme that catalyzes the breakdown of heme into biliverdin, carbon monoxide, and iron. Targeting HO-1 to treat severe COVID-19 has been suggested by several groups, yet the role of HO-1 in SARS-CoV-2 infection remains unclear. Based on this, we aimed to investigate the antiviral activity of Hemin, an activator of HO-1. Infectivity of SARS-CoV-2 was decreased in Vero E6 cells treated with Hemin. Hemin also decreased TMPRSS2 and ACE2 mRNA levels in non-infected cells, possibly explaining the observed decrease in infectivity. TMPRSS2 protein expression and proteolytic activity were decreased in Vero E6 cells treated with Hemin. Besides that, experimental studies supported with in silico calculations. Overall, our study supports further exploration of Hemin as a potential antiviral and inflammatory drug for the treatment of COVID-19.

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“…This inflammatory response involves several host defense systems such as hemostasis, angiogenesis, and complement. 1 , 2 Comorbidities such as diabetes, hypertension, and obesity, as well as advanced age are associated with higher mortality. 3 …”

Section: Introductionmentioning

confidence: 99%

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

Lima

Moraes

Barbosa

et al. 2023

Exp Biol Med (Maywood)

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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.

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Heme/Hemeoxygenase-1 System Is a Potential Therapeutic Intervention for COVID-19 Patients with Severe Complications

Cited by 10 publications

References 12 publications

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity

Hemin shows antiviral activity in vitro, possibly through suppression of viral entry mediators

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

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