COVID-19 Treatments: Chinese Researchers Propose Hydrogen Therapy As An Adjuvant To Treat Severe COVID-19 Patients
: Researchers from the Department of Critical Care Medicine, Sichuan Provincial People's Hospital, Chengdu in China, have in a new study proposed the usage of hydrogen therapy as an adjuvant treatment to treat to severely ill COVID-19 patients.
According to the research team, hydrogen has been shown to have antioxidant, anti-inflammatory, hormone-regulating, and apoptosis-resistance properties, among others. Based on a review of the research, the use of hydrogen might reduce the destructive cytokine storm and lung injury caused by SARS-CoV-2 during COVID-19 in the early stage, stimulating ropy sputum drainage, and ultimately reducing the incidence of severe disease.
The study team says that molecular hydrogen treatment has the potential to become a new adjuvant therapy for COVID-19, but its efficacy and safety require large clinical trials and further confirmation.
The study findings were published in the peer reviewed journal: Frontiers in Pharmacology. https://www.frontiersin.org/articles/10.3389/fphar.2020.543718/full#B9
The COVID-19 pandemic , caused by the SARS-CoV-2 pathogen, has infected over 55.5 million people around the world, and severe forms of the disease have caused more than 1.34 million deaths.
However to date, there are no specific and effective antiviral drugs to treat the severe form of the disease. Similarly, no effective and safe vaccines that could immunize against SARS-CoV-2 are available for use by the general population – and those vaccine candidates currently entering their final stages of approval may not be widely distributed for some time.
The study team explained that hydrogen possesses properties such as antioxidant, anti-inflammatory and hormone-regulating actions. It can also help resist immune-led apoptosis (or programmed cell death) among cells of the body.
The SARS-CoV-2 coronavirus is known to cause cytokine storms or severe inflammatory action in some individuals. This form of cytokine storms is often seen in severe COVID-19 cases and can often result in fatalities. Cytokine storms are known to cause damage to the lungs. Hydrogen therapy, the study team writes, is known to cause "ropy sputum drainage," which reduces the intensity of the disease and can also help as an adjuvant therapy in severe disease.
The team explains that in severe COVID-19, there is a marked rise in plasma levels and of inflammatory markers such as IL-2 (Inter Leukin), IL-7, IL-10, and TNF-α (Tumor necrosis factor). https://pubmed.ncbi.nlm.nih.gov/31986264/
At present, cytokine storms where these features are seen have no specific treatments.
The researchers say that that hydrogen is a "colorless, odorless, and tasteless gas." In 2007, a study published in Nature, showed that inhalation of two percent hydrogen could specifically eliminate the hydroxyl radical (OH) and peroxynitrite anion (ONOO−). https://pubmed.ncbi.nlm.nih.gov/17486089/
It was found that among rats with ischemic injury to the brains, this inhalation could help in reperfusion and correction of ischemic injury, found the researchers. The researchers of the present study note that since then, hydrogen therapy has gathered a lot of interest among researchers and critical care specialists.
The study team says that hydrogen has properties such as "anti-oxidation, anti-inflammation, anti-apoptosis, and hormone regulatory" and thus could potentially find utility in several diseases. Moreover, being small, the hydrogen molecule is capable of reaching the alveoli and thus could help in lung diseases.
Typically in cytokine storms, there is a rise in pro-inflammatory cells and mediators called cytokines such as tumor necrosis factor-α (TNF-α), interleukins (such as IL-1β and IL-6), and interferon-γ (IFN-γ). https://www.nature.com/articles/nri.2017.142/
Upon activation, these cytokines activate the NADPH oxidase in leukocytes or white blood cells. This, in turn, gives rise to reactive oxygen species (ROS), including "superoxide, hydroxyl radicals, and singlet oxygen." These are known to cause damage to several organs. https://pubmed.ncbi.nlm.nih.gov/26189369/
It was found that SARS-CoV-2 induces an interferon-γ-related cytokine storm that leads to severe disease. This form of cytokine storm has also been seen in avian influenza A H5N1 (caused by high viral loads) and Middle East respiratory syndrome (MERS), a betacoronavirus in the same family as SARS-CoV-2. It is usually caused due to high IL-1 β, INF-γ, IP-10, MCP-1, G-CSF, MIP-IA and TNF-α. https://pubmed.ncbi.nlm.nih.gov/16964257/
Several drugs are being tried as treatment options for severe COVID-19, including dexamethasone. https://www.researchgate.net/profile/Vijairam_Selvaraj/publication/342313944_Short-Term_Dexamethasone_in_Sars-CoV-2_Patients/links/5eede6f092851ce9e7f49d47/Short-Term-Dexamethasone-in-Sars-CoV-2-Patients.pdf
Studies have also tried anti-IL6-receptor therapy among these patients. Some researchers have also found that hydrogen can suppress the inward infiltration of the WBCs such as neutrophils and macrophages in lung tissue and also block the action of NF-κB and MPO in lung tissue. It reduces the inflammatory factors and also reduces the cytokine secretion in lung tissue, including TNF-α, IL-1, IL-6, and HMGB1. Hydrogen also removes the ROS, including hydroxyl and peroxynitrate anions and restores normal metabolism of the redox reactions and other ROS. https://pubmed.ncbi.nlm.nih.gov/22508291/
Past research has shown, wrote the researchers, "hydrogen treatment can reduce the levels of TNF-α, IL-1, IL-1 β, IL-6, IL-8, HMGB1, CCL2, and Egr-1 in lung tissue in an animal model". https://pubmed.ncbi.nlm.nih.gov/21184683/
In 45 minutes, hydrogen inhalation can reduce the airway inflammation seen among asthma and COPD patients. https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcaa164/5837119
The study team adds, "Hydrogen can inhibit the Rho/ROCK pathway, increase the expression of ZO-1, and protect lung tissue cells by improving cell-to-cell permeability, and reducing lung injury." https://pubmed.ncbi.nlm.nih.gov/29920028/
The study team thus speculates that hydrogen could play a role in therapy for severe COVID-19 patients with lung injury.
The enzyme superoxide dismutase (SOD) works by protecting the body against antioxidant damage, explain the researchers. Hydrogen therapy has been found to reduce the amounts of malondialdehyde in lung tissues and thus increase the action of SOD. https://pubmed.ncbi.nlm.nih.gov/23739568/
The study team states that critically ill COVID-19 patients often develop multiple organ failure and that hydrogen, due to its properties of antioxidation and anti-apoptosis, could help protect several organs in the body, including the heart, the kidneys and the nervous system. https://pubmed.ncbi.nlm.nih.gov/23316300/
It has been observed that in lung injuries caused by inflammation, viscous secretions fill up the alveoli and clog up the terminal bronchi. Oxygen use given using nasal high-flow oxygen inhalation and non-invasive ventilator-assisted ventilation can help the patients. The researchers added that this positive pressure ventilation mode could also lead to the accumulation of viscous bronchial secretions and ultimately worsen the hypoxia or lack of oxygen at the terminal bronchi. https://pubmed.ncbi.nlm.nih.gov/32198987/
It was reported that hydrogen-enriched water, when used in mucus secretion in smog-induced COPD models of rats, has shown that there is reduced secretion and relief of hypoxia. The team writes, "early hydrogen inhalation may promote sputum dilution, improve small airway resistance, and relieve dyspnea." https://pubmed.ncbi.nlm.nih.gov/24376700/
Among some of the safety concerns include the fact that it is flammable and explosive, but less than 4 percent together with oxygen at room temperature is not combustible. No serious side effects are seen with hydrogen use. Some complain of heartburn, constipation and headache. https://pubmed.ncbi.nlm.nih.gov/29058596/
The researchers believe that hydrogen therapy could be used among severe COVID-19 patients with success. They write, "In the future, more large-scale randomized controlled trials are needed to verify the efficacy and safety of this treatment clinically."
The study team hypothesizes that the early use of hydrogen might mitigate the destruction caused by the cytokine storm associated with COVID-19, reducing lung injury, promoting viscous sputum drainage, and thus reducing the incidence of critically ill patients.
To date, there is only one published study mentioning the use of hydrogen to treat COVID-19 patients. https://pubmed.ncbi.nlm.nih.gov/32642277/
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