The Influence of Molecular Hydrogen Therapies in Managing the Symptoms of Acute and Chronic COVID-19

Main Article Content

Grace Russell AD Thomas Alexander Nenov John T Hancock

Abstract

Coronavirus Infectious Disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) that emerged as a novel pathogen of global concern in the latter stages of 2019. COVID-19 is a highly contagious disease which can be transmitted through aerosol droplets and surface-to-host contact. Both symptomology and the severity of disease can vary wildly between individuals, from asymptomatic but infectious, to those that require critical care. Due to the neoteric emergence of SARS-CoV-2, current treatment strategies are not yet well developed and rely on the repurposing of such medications as antiviral, corticosteroid, immunosuppressant and oxygen (O2) therapies. However, the minimal efficacy of these interventions is concerning. In addition to the acute infection that prevails, it is estimated that up to 30% of adults who contract COVID-19 develop chronic symptoms lasting longer than 12 weeks. It is also estimated that 15% of children aged 2-16 years have developed long-lasting sequelae associated with SARS-CoV-2 infection.


According to recent clinical data, molecular hydrogen (H2) and oxy-hydrogen (H2/O2) therapies successfully remediated the debilitating effects of SARS-CoV-2 infection in adults. By acting as an effective anti-inflammatory and antioxidative agent, it is reported that H2 administration can improve recovery through abatement of the hyperinflammatory cytokine cascade and reduction of inhalation resistance in patients with mild-moderate disease symptoms.


In this review, the authors investigate the clinical and empirical evidence relating to treating the symptoms of both acute and chronic COVID-19 with H2-containing therapeutics.

Article Details

How to Cite
RUSSELL, Grace et al. The Influence of Molecular Hydrogen Therapies in Managing the Symptoms of Acute and Chronic COVID-19. Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3036>. Date accessed: 22 dec. 2024. doi: https://doi.org/10.18103/mra.v10i9.3036.
Section
Research Articles

References

1. Russell G, Rehman M, LeBaron TW, Veal D, Adukwu E and Hancock JT. An overview of SARS-CoV-2 (COVID-19) infection and the importance of molecular hydrogen as an adjunctive therapy. Reactive Oxygen Species. 2020;10(28):150-165. Doi: 10.20455/ros.2020.829
2. Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L, Holmes EC, Zhang YZ. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265-269. doi: 10.1038/s41586-020-2008-3.
3. Cucinotta D and Vanelli M. WHO declares COVID-19 a pandemic. Acta Bio Medica: Atenei Parmensis. 2020;91(1):157. Doi: 10.23750/abm.v91i1.9397.
4. Lucas K, Rosch M and Langguth P. Molecular hydrogen (H2) as a potential treatment for acute and chronic fatigue. Archiv der Pharmazie. 2021;354(4): 2000378. Doi:10.1002/ardp.202000378
5. Li Y, Wang Z, Wang Y, Zheng W and Xie K. Molecular Hydrogen: A Promising Adjunctive Strategy for COVID-19 treatment. Frontiers in Medicine. 2021; 8:671215. Doi: 10.3389/fmed.2021.671215
6. Larsen JR, Martin MR, Martin JD, Kuhn P and Hicks JB. Modeling the onset of symptoms of COVID-19. Frontiers in public health. 2020;8:473. Doi: 10.3389/fpubh.2020.00473
7. World Health Organization. Coronavirus disease 2019 (‎COVID-19)‎: situation report, 46 [03/06/2020]. World Health Organization. Retrieved from: https://apps.who.int/iris/handle/10665/331443 [Accessed 03/07/2022]
8. Karim SA. COVID-19 vaccine affordability and accessibility. The Lancet. 2020;396(10246):238. Doi: 10.1016/s0140-6736(20)31540-3
9. Follmann D, Fintzi J, Fay MP, Janes HE, Baden L, El Sahly H, et al. Assessing durability of vaccine effect following blinded crossover in COVID-19 vaccine efficacy trials. medRxiv [Preprint 12/14/2020]. Doi: 10.1101/2020.12.14.20248137
10. Raveendran AV and Misra A. Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management. Diabetes & Metabolic Syndrome: Clin. Res. & Revs. 2021;15(5):102235. Doi: 10.1016/j.dsx.2021.102235
11. Hardelid P, Favarato G, Wijlaars L, Fenton L, McMenamin J, Clemens T, et al. S. Risk of SARS-CoV-2 testing, PCR-confirmed infections and COVID-19-related hospital admissions in children and young people: Birth cohort study. medRxiv [Preprint 01/05/2022]. Doi: 10.1101/2021.12.17.21267350
12. Garg M, Maralakunte M, Garg S, Dhooria, S, Sehgal I, Bhalla AS. et al. The conundrum of ‘long-COVID-19: a narrative review. Int. jrnl of gen. med. 2021;14:2491. Doi: 10.2147/IJGM.S316708
13. National Institute for Health and Care Excellence (NICE), Royal College of General Practitioners, Healthcare Improvement Scotland SIGN [11/11/2021]. COVID-19 Rapid Guideline: Managing the Long-Term Effects of COVID-19. National Institute for Health and Care Excellence; London, UK. Available online: www.nice.org.uk/guidance/ng188 [Accessed 05/07/2022]
14. Salamanna F, Veronesi F, Martini L, Landini MP and Fini M. Post-COVID-19 syndrome: the persistent symptoms at the post-viral stage of the disease. A systematic review of the current data. Frontiers in medicine. 2021;8:653516. Doi: 10.3389/fmed.2021.653516
15. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature medicine. 2007;13(6): 688-694. Doi: 10.1038/nm1577
16. Kamimura N, Nishimaki K, Ohsawa I and Ohta S. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity. 2011;19(7):1396-1403. Doi: 10.1038/oby.2011.6
17. Higashimura Y, Baba Y, Inoue R, Takagi T, Uchiyama K, Mizushima K, et al. Effects of molecular hydrogen-dissolved alkaline electrolyzed water on intestinal environment in mice. Med. gas res. 2018;8(1):6. Doi: 10.4103/2045-9912.229597
18. Nascimento G and Del Bel E. Molecular hydrogen inhalation prevents L-DOPA-induced dyskinesia in a Parkinson's disease rat model. Authorea Preprints. 15/02/2022. Retrieved from: https://d197for5662m48.cloudfront.net/documents/publicationstatus/76378/preprint_pdf/fcfd82d67b0a2493d6965d9d885fecda.pdf. [Accessed 12/07/2022]
19. UMIN Clinical Trials Registry. Retrieved from: http://virtual3.umin.ac.jp/ctr/index.htm [Accessed 06/07/2022]
20. ICTRP Search Portal (who.int.) Retrieved from: https://trialsearch.who.int/ [Accessed 06/07/2022]
21. Chinese Clinical Trial Register (ChiCTR). Retrieved from: https://www.chictr.org.cn/searchprojen.aspx?title=hydrogen&officialname=&subjectid=&secondaryid=&applier=&studyleader=ðicalcommitteesanction=&sponsor=&studyailment=&studyailmentcode=&studytype=0&studystage=0&studydesign=0&minstudyexecutetime=&ma&maxstudyexecutetime=&recruitmentstatus=0&gender=0&agreetosign=&secsponsor=®no=®status=0&country=&province=&city=&institution=&institutionlevel=&measure=&intercode=&sourceofspends=&createyear=0&isuploadrf=&whetherpublic=&btngo=btn&verifycode=&page=1 [Accessed 06/07/2022]
22. ClinicalTrials.gov Retrieved from: https://clinicaltrials.gov/ct2/results?cond=&term=molecular+hydrogen&cntry=&state=&city=&dist= [Accessed 06/07/2022]
23. Russell G, Nenov A and Hancock JT. Oxy-hydrogen gas: The rationale behind its use as a novel and sustainable treatment for COVID-19 and other respiratory diseases. Eur. Med. J. 2021;21-27. Doi: 10.33590/emj/21-00027
24. LeBaron TW, McCullough ML and Ruppman Sr KH. A novel functional beverage for COVID-19 and other conditions: hypothesis and preliminary data, increased blood flow, and wound healing. Journal of Translational Science. 2020;6(6):4-6. Doi: 10.15761/JTS.1000380
25. Slezák J, Kura, B, Frimmel K, Zálešák M, Ravingerová T, Viczenczová C et al. Preventive and therapeutic application of molecular hydrogen in situations with excessive production of free radicals. Physiological Res. 2016;65. Doi: 10.33549/physiolres.933414
26. Kura, B, Bagchi A.K, Singal P.K, Barancik M, LeBaron TW, Valachova K. Molecular hydrogen: Potential in mitigating oxidative-stress-induced radiation injury. Can. Jrn. of Phys. and Pharm. 2019;97(4):287-292. Doi: 10.1139/cjpp-2018-0604
27. SARS-CoV-2 Variant Classifications and Definitions. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html [Accessed 08/06/2022]
28. Zoe Health Study - COVID Data (joinzoe.com) Retrieved from: https://covid.joinzoe.com/post/omicron-and-cold-like-symptoms-rapidly-taking-over-in-london. [Accessed 10/06/2022]
29. Alexandar S, Ravisankar M, Kumar RS and Jakkan K. A comprehensive review on Covid-19 Delta variant. International Journal of Pharmacology and Clin. Res. (IJPCR). 2021;5(7):83-85. Doi:
30. Iacobucci G. Covid-19: Runny nose, headache, and fatigue are commonest symptoms of omicron, early data show. BMJ (Clinical research ed.). 2021;375:3103. Doi: 10.1136/bmj.n3103
31. Epidemiological update: SARS-CoV-2 Omicron sub-lineages BA.4 and BA.5 (europa.eu). Retrieved from: https://www.ecdc.europa.eu/en/news-events/epidemiological-update-sars-cov-2-omicron-sub-lineages-ba4-and-ba5. [Accessed 06//2022]
32. COVID-19 vaccines (who.int). Retrieved from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines [Accessed 04/07/2022]
33. Vitiello A, Ferrara F, Troiano V and La Porta R. COVID-19 vaccines and decreased transmission of SARS-CoV-2. Inflammopharmacology. 2021;29(5):1357-1360. Doi: 10.1007/s10787-021-00847-2
34. Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC et al. Remdesivir for the treatment of Covid-19. New England Journal of Medicine. 2020;383(19):1813-1826. Doi: 10.1056/NEJMoa2007764
35. Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M and Martinez-de-Hoyo R. The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Sci. repts. 2021;11(1):1-11. Doi: 10.1038/s41598-021-90551-6
36. Piscoya A, Ng-Sueng LF, Parra del Riego A, Cerna-Viacava R, Pasupuleti V, Roman YM et al. Efficacy and harms of remdesivir for the treatment of COVID-19: A systematic review and meta-analysis. PloS one. 2020;15(12):0243705. Doi: 10.1371/journal.pone.0243705
37. Vegivinti CTR, Evanson KW, Lyons H, Akosman I, Barrett A, Hardy N et al. Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials. BMC Infectious Diseases. 2022;22(1):1-45. Doi: 10.1186/s12879-022-07068-0
38. Ahmadikia K, Hashemi SJ, Khodavaisy S, Getso MI, Alijani N, Badali H. The double‐edged sword of systemic corticosteroid therapy in viral pneumonia: A case report and comparative review of influenza‐associated mucormycosis versus COVID‐19 associated mucormycosis. Mycoses. 2021;64(8):798-808. Doi: 10.1111/myc.13256
39. Perantie DC and Brown ES. Corticosteroids, immune suppression, and psychosis. Curr. psych. repts. 2002;4(3):171-176. Doi: 10.1007/s11920-002-0023-8
40. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infectious diseases. 2022;53(10):737-754. Doi: 10.1080/23744235.2021.1924397
41. Lyons C and Callaghan M. The use of high‐flow nasal oxygen in COVID‐19. Anaesthesia. 2020;75(7):843-847. Doi: 10.1111/anae.15073
42. Ng Z, Tay WC and Ho CHB. Awake prone positioning for non-intubated oxygen dependent COVID-19 pneumonia patients. Euro. Resp. Jrn. 2020;56(1). Doi: 10.1183/13993003.01198-2020
43. Suzuki A, Ito M, Hamaguchi T, Mori H, Takeda Y, Baba R et al. Quantification of hydrogen production by intestinal bacteria that are specifically dysregulated in Parkinson's disease. PLoS One. 2018;13(12):0208313. Doi: 10.1371/journal.pone.0208313
44. ZetterstrÖm, A. Deep-sea diving with synthetic gas mixtures. The Military Surgeon (United States). 1948;103(2):104-106. Doi: 10.1093/milmed/103.2.104
45. Chen JB, Kong XF, Qian W, Mu F, Lu TY, Lu YY et al. Two weeks of hydrogen inhalation can significantly reverse adaptive and innate immune system senescence patients with advanced non-small cell lung cancer: a self-controlled study. Med. Gas Res. 2020;10(4):149. Doi: 10.4103/2045-9912.304221
46. Zheng ZG, Sun WZ, Hu JY, Jie ZJ, Xu JF, Cao J et al. Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Resp. res. 2021;22(1):1-12. Doi: 10.1186/s12931-021-01740-w
47. Guan WJ, Wei CH, Chen AL, Sun XC, Guo GY, Zou X et al. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. Jrnl of Thoracic Disease. 2020;12(6):3448. Doi: 10.21037/jtd-2020-057
48. Huang CS, Kawamura T, Toyoda Y and Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free rad. res. 2010;44(9):971-982. Doi: 10.3109/10715762.2010.500328
49. GRASNotices(fda.gov). Retrieved from: https://www.cfsanappsexternal.fda.gov/scripts/fdcc/?set=GRASNotices&id=520&sort=GRN_No&order=DESC&startrow=1&type=basic&search=hydrogen. [Accessed 14/07/2022]
50. Alwazeer D, Liu FF, Wu XY and LeBaron TW. Combating Oxidative Stress and Inflammation in COVID-19 by Molecular Hydrogen Therapy: Mechanisms and Perspectives. Oxidative Med. and Cell. Longevity. 5513868-5513868.
51. Commission Regulation (EU) No 1129/2011 of 11 November 2011 amending Annex II to Regulation (EC) No 1333/2008 of the European Parliament and of the Council by establishing a Union list of food additives Text with EEA relevance. Document number: 32011R1129. (europa.eu). Retrieved from: https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A32011R1129 [Accessed 14/07/2022]
52. Approved additives and E numbers | Food Standards Agency. Retrieved from: https://www.food.gov.uk/business-guidance/approved-additives-and-e-numbers [Accessed 14/07/2022]
53. Green SJ. Covid-19 accelerates endothelial dysfunction and nitric oxide deficiency. Microbes and infection. 2020;22(4):149. Doi: 10.1016/j.micinf.2020.05.006
54. Zubieta-Calleja G and Zubieta-DeUrioste N. Pneumolysis and “silent hypoxemia” in COVID-19. Indian Journal of Clin. Biochem. 2021;36(1):112-116. Doi: 10.1007/s12291-020-00935-0
55. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ and Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. Jama. 2020;324(8):782-793. Doi: 10.1001/jama.2020.12839
56. Ostojic SM. Molecular hydrogen: an inert gas turns clinically effective. Annals of medicine. 2015;47(4):301-304. Doi: 10.3109/07853890.2015.1034765
57. Wu D, Liang M, Dang H, Fang F, Xu F and Liu C. Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway. Biochem. and biophys. res. comms. 2018;495(2):1620-1627. Doi: 10.1016/j.bbrc.2017.11.193
58. Zhang N, Deng C, Zhang X, Zhang J and Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asth. res. and practice. 2018;4(1):1-9. Doi: 10.1186/s40733-018-0040-y
59. Luo P, Ding Y, He Y, Chen D, He Q, Huang Z et al. Hydrogen-oxygen therapy alleviates clinical symptoms in twelve patients hospitalized with COVID-19: A retrospective study of medical records. Medicine. 2022;101,(9):27759. Doi: 10.1097/MD.0000000000027759
60. Botek M, Krejčí J, McKune AJ, Sládečková B and Naumovski N. Hydrogen rich water improved ventilatory, perceptual and lactate responses to exercise. Int. jrnl of sports med. 2019;40(14),879-885. Doi: 10.1055/a-0991-0268
61. Li Q, Hu L, Li J, Yu P, Hu F, Wan B et al. Hydrogen attenuates endotoxin-induced lung injury by activating thioredoxin 1 and decreasing tissue factor expression. Frontiers in Immunology. 2021;12:625957. Doi: 10.3389/fimmu.2021.6259
62. Botek M, Krejčí J, Valenta M, McKune A, Sládečková B, Konečný P et al. Molecular hydrogen positively affects physical and respiratory function in acute post-COVID-19 patients: A new perspective in rehabilitation. Int. jrnl of enviro. res. and pub. health. 2022;19(4):1992. Doi: 10.3390/ijerph19041992
63. Ohta S. Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications. Methods in enzymology. 2015;555:289-317. Doi: 10.1016/bs.mie.2014.11.038
64. Slezak J, Kura B, LeBaron TW, Singal PK, Buday J and Barancik M. Oxidative stress and pathways of molecular hydrogen effects in medicine. Curr. Pharm. Des. 2021;27(5):610-625. Doi: 10.2174/1381612826666200821114016
65. Naqvi I, Giroux N, Olson L, Morrison SA, Llanga T, Akinade TO et al. DAMPs/PAMPs induce monocytic TLR activation and tolerance in COVID-19 patients; nucleic acid binding scavengers can counteract such TLR agonists. Biomaterials. 2022;283:121393. Doi: 10.1016/j.biomaterials.2022.121393
66. Chernyak BV, Lyamzaev KG and Mulkidjanian AY. Innate Immunity as an Executor of the Programmed Death of Individual Organisms for the Benefit of the Entire Population. Int. jrnl of mol. sci. 2021;22(24):13480. Doi: 10.3390/ijms222413480
67. Fodil S and Annane D. Complement inhibition and COVID-19: the story so far. ImmunoTargets and Therapy. 2021;10:273. Doi: 10.2147/ITT.S284830
68. Itoh T, Fujita Y, Ito M, Masuda A, Ohno K, Ichihara M et al. Molecular hydrogen suppresses FcεRI-mediated signal transduction and prevents degranulation of mast cells. Biochem. and biophys. res. comms. 2009;389(4):651-656. Doi: 10.1016/j.bbrc.2009.09.047
69. Huang P, Wei S, Huang W, Wu P, Chen S, Tao A et al. Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model. Int. Immunopharmacology. 2019;74:05646. Doi: 10.1016/j.intimp.2019.05.031
70. Nogueira JE, Passaglia P, Mota CM, Santos BM, Batalhão ME, Carnio EC et al. Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status. Free rad. bio. and med. 2018;129:186-193. Doi: 10.1016/j.freeradbiomed.2018.09.028
71. Yao L, Chen H, Wu Q and Xie K. Hydrogen-rich saline alleviates inflammation and apoptosis in myocardial I/R injury via PINK-mediated autophagy. Int. jrnl. of mol. Med. 2019;44(3):1048-1062. Doi: 10.3892/ijmm.2019.4264
72. Hirano SI, Ichikawa Y, Sato B, Yamamoto H, Takefuji Y and Satoh F. Potential therapeutic applications of hydrogen in chronic inflammatory diseases: possible inhibiting role on mitochondrial stress. Int. jrnl. of mol. sci. 2021;22(5):2549. Doi: 10.3390/ijms22052549
73. Xie K, Yu Y, Huang Y, Zheng L, Li J, Chen H et al. Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis. Shock. 2012;37(5):548-555. Doi: 10.1097/SHK.0b013e31824ddc81
74. Zhang N, Deng C, Zhang X, Zhang J and Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asth. res. and practice. 2018;4(1):1-9. Doi: 10.1186/s40733-018-0040-y
75. Gharib B, Hanna S, Abdallahi OM, Lepidi H, Gardette B and De Reggi M. Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation. Comptes Rendus de l'Académie des Sciences-Series III-Sciences de la Vie. 2001;324(8):719-724. Doi: 10.1016/S0764-4469(01)01350-6
76. Hirano SI, Ichikawa Y, Sato B, Yamamoto H, Takefuji Y and Satoh F. Molecular hydrogen as a potential clinically applicable radioprotective agent. Int. jrnl of mol. Sci. 2021;22(9):4566. Doi: 10.3390/ijms22094566
77. Fang W, Tang L, Wang G, Lin J, Liao W, Pan W et al. Molecular hydrogen protects human melanocytes from oxidative stress by activating Nrf2 signaling. jrnl of inves. derm. 2020;140(11):2230-2241. Doi: 10.1016/j.jid.2019.03.1165
78. Ahmed SMU, Luo L, Namani A, Wang XJ and Tang X. Nrf2 signaling pathway: Pivotal roles in inflammation. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2017;1863(2):585-597. Doi: 10.1016/j.bbadis.2016.11.005
79. Loboda A, Damulewicz M, Pyza E, Jozkowicz A and Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell. and mol. life sci. 2016;73(17):3221-3247. Doi: 10.1007/s00018-016-2223-0
80. What is Post-COVID Syndrome (postcovidsyndromebsol.nhs.uk) Retrieved from: https://www.postcovidsyndromebsol.nhs.uk/index.php/what-is-post-covid-syndrome [Accessed 16/07/2022]
81. Fernández-de-Las-Peñas C, Palacios-Ceña D, Gómez-Mayordomo V, Cuadrado ML and Florencio LL. Defining post-COVID symptoms (post-acute COVID, long COVID, persistent post-COVID): an integrative classification. Int. jrnl. of enviro. res. and pub. health. 2021;18(5):2621. Doi: 10.3390/ijerph18052621
82. Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK - Office for National Statistics (ons.gov.uk). Retrieved from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/1april2021 [Accessed 16/07/2022]
83. Mandal S, Barnett J, Brill SE, Brown JS, Denneny EK, Hare SS et al. ‘Long-COVID’: a cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax. 2021;76(4):396-398. Doi: 10.1136/thoraxjnl-2020-215818
84. Yan Z, Yang M and Lai CL. Long COVID-19 syndrome: a comprehensive review of its effect on various organ systems and recommendation on rehabilitation plans. Biomedicines. 2021;9(8):966. Doi: 10.3390/biomedicines9080966
85. Davenport TE, Lehnen M, Stevens SR, VanNess JM, Stevens J and Snell CR. Chronotropic intolerance: an overlooked determinant of symptoms and activity limitation in myalgic encephalomyelitis/chronic fatigue syndrome? Frontiers in Pediatrics. 2019;7:82. Doi: 10.3389/fped.2019.00082
86. Jason, LA, Islam MF, Conroy K, Cotler J, Torres, C, Johnson M et al. COVID-19 symptoms over time: comparing long-haulers to ME/CFS. Fatigue: biomedicine, health & behavior. 2021;9(2):59-68. Doi: 10.1080/21641846.2021.1922140
87. Wong TL and Weitzer DJ. Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—a systemic review and comparison of clinical presentation and symptomatology. Medicina. 2021;57(5):418. Doi: 10.3390/medicina57050418
88. Shibayama Y, Dobashi S, Arisawa T, Fukuoka T and Koyama K. Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men. Med. gas res. 2020;10(4):155. Doi: 10.4103/2045-9912.304222
89. Hirano SI, Ichikawa Y, Sato B, Takefuji Y and Satoh F. Molecular Hydrogen as a Medical Gas for the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Efficacy Based on a Literature Review. Frontiers in Neurology. 2022;673. Doi: 10.3389/fneur.2022.84131
90. Milovancev A, Avakumovic J, Drid P, Todorovic N, Stajer V and Ostojic SM. Hydrogen-rich water alleviates inflammation and fatigue in COVID-19: A pilot study. Euro. jrnl of inflamm. 2022;20:1-3. Doi: 10.1177/1721727X221094197
91. Singh RB, Halabi G, Fatima G, Rai RH, Tarnava AT and LeBaron TW. Molecular hydrogen as an adjuvant therapy may be associated with increased oxygen saturation and improved exercise tolerance in a COVID‐19 patient. Clin. Case Repts. 2021;9(11):5039. Doi: 10.1002/ccr3.5039
92. Friedberg F. and Choi D. Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial. Fatigue: Biomedicine, Health & Behavior. 2022;10(1):26-39. Doi: 10.1080/21641846.2022.2038519
93. Buggey J. and ElAmm CA. Myocarditis and cardiomyopathy. Current opinion in cardiology. 2018;33(3):341-346. Doi: 10.1097/HCO.0000000000000514
94. Izzo C, Vitillo P, Di Pietro P, Visco V, Strianese A, Virtuoso, N et al. The role of oxidative stress in cardiovascular aging and cardiovascular diseases. Life. 2021;11(1):60. Doi: 10.3390/life11010060
95. LeBaron TW., Kura B, Kalocayova B, Tribulova N. and Slezak, J. A new approach for the prevention and treatment of cardiovascular disorders. Molecular hydrogen significantly reduces the effects of oxidative stress. Molecules. 2019;24(11):2076. Doi: 10.3390/molecules24112076
96. Barancik M, Kura B, LeBaron TW, Bolli R, Buday J and Slezak J. Molecular and cellular mechanisms associated with effects of molecular hydrogen in cardiovascular and central nervous systems. Antioxidants. 2020;9(12):1281.
Doi: 10.3390/antiox9121281
97. Katsumata Y, Sano F, Abe T, Tamura T, Fujisawa T, Shiraishi Y et al. The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling After Percutaneous Coronary Intervention for ST-Elevated Myocardial Infarction-First Pilot Study in Humans. Circulation jrnl. 2017;81(7):940-947. Doi: 10.1253/circj.CJ-17-0105
98. Tamura T, Hayashida K, Sano M, Suzuki M, Shibusawa T, Yoshizawa J et al. Feasibility and safety of hydrogen gas inhalation for post-cardiac arrest syndrome–first-in-human pilot study. Circulation jrnl. 2016:80(8):1870-1873. Doi: 10.1253/circj.CJ-16-0127
99. Tamura T, Suzuki M, Hayashida K, Kobayashi Y, Yoshizawa J, Shibusawa T et al. Hydrogen gas inhalation alleviates oxidative stress in patients with post-cardiac arrest syndrome. Jrnl. of clin. biochem. and nutrition. 2020;67(2):214-221. Doi: 10.3164/jcbn.19-101
100. Chen KD, Lin WC and Kuo HC. Chemical and biochemical aspects of molecular hydrogen in treating Kawasaki Disease and COVID-19. Chem. Res. in Tox. 2021;34(4):952-958. Doi: 10.1021/acs.chemrestox.0c00456
101. Zhang Y, Tan S, Xu J and Wang T. Hydrogen therapy in cardiovascular and metabolic diseases: from bench to bedside. Cell. physio .and biochem. 2018;47(1):1-10. Doi: 10.1159/000489737
102. Dong G, Fu J, Bao D and Zhou J. Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery in Dragon Boat Athletes: Evidence from a Pilot Study. Int. jrnl. of enviro. res. and pub. health. 2022;19(9):5413. Doi: 10.3390/ijerph19095413
103. Jesus AA, Passaglia P, Santos BM, Rodrigues-Santos, I, Flores RA, Batalhao ME. Chronic molecular hydrogen inhalation mitigates short and long-term memory loss in polymicrobial sepsis. Brain res. 2020;1739:146857.
Doi: 10.1016/j.brainres.2020.146857
104. Nishimaki, K, Asada T, Ohsawa I, Nakajima E, Ikejima C, Yokota T et al. Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment. Curr. Alzheimer res. 2018;15(5):482-492. Doi: 10.2174/1567205014666171106145017
105. Mizuno K, Sasaki AT, Ebisu K, Tajima K, Kajimoto O, Nojima J et al. Hydrogen-rich water for improvements of mood, anxiety, and autonomic nerve function in daily life. Med. gas res. 2017;7(4):247. Doi: 10.4103/2045-9912.222448
106. Russell G, Nenov A, Kisher H and Hancock JT. Molecular Hydrogen as Medicine: An Assessment of Administration Methods. Hydrogen. 2021;2(4):444-460. Doi: 10.3390/hydrogen2040025