COVID-19 and heme oxygenase: novel insight into the disease and potential therapies

Philip L Hooper, Philip L Hooper

Abstract

The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19's heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection's damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.

Keywords: Anesthesia; COVID-19; Cytokine storm; Elderly; Estrogen; Heat shock proteins; Heme oxygenase; Inflammation; Smoking; Therapy; Ventilator.

Figures

Fig. 1
Fig. 1
Cytokine, endotoxin, and microbial agents released from the acute lung injury/acute respiratory distress syndrome (ALI/ ARDS) lung during injurious mechanical ventilation. Mechanical ventilation–associated and mechanical ventilation–induced lung injury causes impairment of the integrity of the alveolar-capillary membrane and results in augmented cytokine release leading to translocation of cytokines/endotoxin/microbial agents from the lung to the circulation, contributing to systemic inflammation and a multi-organ dysfunction syndrome. With permission (Belperio et al. 2006)

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