COVID-19 and heme oxygenase: novel insight into the disease and potential therapies
Philip L Hooper
Cell Stress and Chaperones, doi:10.1007/s12192-020-01126-9
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 cigarettesmokers 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.
References
Abouhashem, Singh, Azzazy, Sen, Is low alveolar type II cell SOD3 in the lungs of elderly linked to the observed severity of COVID-19?, Antioxid Redox Signal,
doi:10.1089/ars.2020.8111
Aggarwal, Gupta, Sung, Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers,
doi:10.1111/bph.12131
Anderson, Reiter, Melatonin: roles in influenza, Covid-19, and other viral infections, Rev Med Virol,
doi:10.1002/rmv.2109
Baglole, Sime, Phipps, Cigarette smoke-induced expression of heme oxygenase-1 in human lung fibroblasts is regulated by intracellular glutathione, Am J Physiol Lung Cell Mol Physiol,
doi:10.1152/ajplung.90215.2008
Belperio, Keane, Lynch, Strieter, Ali et al., The role of cytokines during the pathogenesis of ventilatorassociated and ventilator-induced, Lung Injury,
doi:10.1055/s-2006-948289
Bloomer, Zhang, Brown, Kregel, Differential regulation of hepatic heme oxygenase-1 protein with aging and heat stress, J Gerontol A Biol Sci Med Sci,
doi:10.1093/gerona/gln056
Brioni, Varughese, Ahmed, Bein, A clinical review of inhalation anesthesia with sevoflurane: from early research to emerging topics, J Anesth,
doi:10.1007/s00540-017-2375-6
Chen, Wang, Xie, Chen, Zhu et al., Heme oxygenase-1 reduces sepsis-induced endoplasmic reticulum stress and acute, Lung Injury,
doi:10.1155/2018/9413876
De Maio, Hightower, COVID-19, acute respiratory distress syndrome (ARDS), and hyperbaric oxygen therapy (HBOT): what is the link?, Cell Stress Chaperones,
doi:10.1007/s12192-020-01121-0
El Kalamouni, Frumence, Bos, Turpin, Nativel et al., Subversion of the heme oxygenase-1 antiviral activity by zika virus, Viruses,
doi:10.3390/v11010002
El-Hawary, Ss, Ali, Younis, Hepatoprotective potential of standardized Ficus species in intrahepatic cholestasis rat model: involvement of nuclear factor-κB, and Farnesoid X receptor signaling pathways, J Ethnopharmacol,
doi:10.1016/j.jep.2018.11.026
Espinoza, León, Céspedes, Gómez, Canedo-Marroquín et al., Heme oxygenase-1 modulates human respiratory syncytial virus replication and lung pathogenesis during infection, J Immunol,
doi:10.4049/jimmunol.1601414
Fedson, Jacobson, Rordam, Opal, Treating the host response to ebola virus disease with generic statins and angiotensin receptor blockers, mBIO,
doi:10.1128/mBio.00716-15
Fujioka, Kalish, Zhao, Lu, Wong et al., Induction of heme oxygenase-1 attenuates the severity of sepsis in a non-surgical preterm mouse model, Shock,
doi:10.1097/SHK.0000000000000689
Geier, Da ; Godman, Chheda, Hightower, Perdrizet et al., Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells, Cell Stress Chaperones,
doi:10.1007/s12192-009-0159-0
Hooper, Balogh, Rivas, Kavanagh, Vigh, The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes, Cell Stress and Chaperones,
doi:10.1007/s12192-014-0493-8
Hooper, Hightower, Hooper, Loss of stress response as a consequence of viral infection: implications for disease and therapy, Cell Stress Chaperones,
doi:10.1007/s12192-012-0352-4
Hooper, Hooper, Loss of defense against stress: diabetes and heat shock proteins, Diabetes Technol Ther,
doi:10.1089/dia.2005.7.204
Hornuss, Firsching, Dolch, Martignoni, Peraud et al., Long-term isoflurane therapy for refractory bronchospasm associated with herpes simplex pneumonia in a heart transplant patient, Case Rep Med,
doi:10.1155/2010/746263
Hsu, Yeh, Chen, Kuo, Lin et al., Role of Akt/HO-1 pathway in estrogen-mediated attenuation of trauma-hemorrhage-induced lung injury, J Surg Res,
doi:10.1016/j.jss.2012.10.926
Huang, Falgout, Takeda, Yamada, Dhawan, Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication, Virology,
doi:10.1016/j.virol.2016.12.019
Kapetanovic, Muzzio, Huang, Thompson, Mccormick, Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats, Cancer Chemother Pharmacol,
doi:10.1007/s00280-010-1525-4
Lindenfeld, Ghali, Krause-Steinrauf, Khan, Adams et al., Hormone replacement therapy is associated with improved survival in women with advanced heart failure, J Am Coll Cardiol,
doi:10.1016/S0735-1097(03)00938-0
Moghadamtousi, Kadir, Hassandarvish, Tajik, Abubakar et al., A review on antibacterial, antiviral, and antifungal activity of curcumin, Biomed Res Int,
doi:10.1155/2014/186864
Nacoti, Colombo, Fochi, Bonacina, Fazzi et al., series of infants with severe bronchiolitis-induced acute respiratory distress syndrome,
doi:10.1002/ccr3.1490
Patriarca, Furfaro, Cosso, Maineri, Balbis et al., Heme oxygenase 1 expression in rat liver during ageing and ethanol intoxication, Biogerontology,
doi:10.1007/s10522-006-9079-x
Richardson, Hirsch, Narasimhan, Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the,
doi:10.1001/jama.2020.6775
Shi, Lei, Tang, Wang, Xia, Melatonin attenuates acute kidney ischemia / reperfusion injury in diabetic rats by activation of the SIRT1 / Nrf2 / HO-1 signaling pathway
Suba, Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients; an opinion paper
Takeda, Sasai, Adachi, Ohnishi, Fujisawa et al., Potential role of heme metabolism in the inducible expression of heme oxygenase-1, Biochim Biophys Acta Gen Subj,
doi:10.1016/j.bbagen.2017.03.018
Yang, Li, Wu, Liu, Ni et al., Anti-oxidant effect of heme oxygenase-1 on cigarette smokeinduced vascular injury, Mol Med Rep,
doi:10.3892/mmr.2015.3722