FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, March 22, 2023

Further Insights into Covid-19 Etiology and Susceptibility

by Michael Passwater

OMNS (March 22, 2023) As we pass the three-year anniversary of the World Health Organization's declaration of Covid-19 as a global pandemic, more than 6.8 million deaths have been attributed to the SARS-CoV-2 virus with 1.1 million (16%) of those deaths occurring in the United States. Over 6 million Covid-19 patients have been hospitalized in the United States. Over five billion people have been vaccinated including 230 million people in the United States. [1] Yet there is still no consensus on the most effective treatment. From 2020 onward, informed by past experiences with infectious diseases, genomic analysis of coronaviruses, and early treatment efforts, some natural medicine advocates have suggested that adequate doses of glutathione, vitamin C, selenium, zinc, and vitamin D may be helpful. [2-10]

Two recent studies deepen our understanding of how SARS-CoV-2 attacks our cells and tissues, and which individuals are at risk of becoming seriously ill from the infection. A study of 106 people in North Carolina with Covid-19 in late 2020 (all unvaccinated) showed selenium intake to be inversely related to Covid severity index among those with below average selenium and zinc intake (higher selenium intake = lower disease severity). [11] This is consistent with population studies in 2020 and 2021 in China associating more severe disease and mortality with lower regional selenium levels, and retrospective studies of hospitalized patients with Covid-19 in Germany identifying low total serum selenium and selenoprotein P status, along with advanced age and low zinc levels, as predictors of mortality. [12-15]

A recent mechanistic study also confirmed the previously predicted destruction of host selenoproteins thioredoxin reductase 1 (TXNRD1), selenoprotein P (SelenoP), and selenoprotein F (SelenoF) by the SARS-CoV-2 Mpro protein. Additionally, this viral protease was shown to destroy glutamate-cysteine ligase catalytic subunit (GCLC) which is a rate limiting enzyme in the production of glutathione. Destruction of TXNRD1, SelenoP, SelenoF, and GCLC weakens host immune and antioxidant defenses, genetic replication "proof-reading", and hemostasis while also supporting a shift from DNA to RNA production within the cell - effectively hijacking the cell to become an RNA virus factory instead of a host DNA factory. [16]

Together, these new publications add support to the central roles of selenoproteins (proteins containing one or more selenocysteine amino acids) and the sulfur containing antioxidant glutathione in preventing Covid-19 and similar infections. This is also consistent with successful studies that have suggested the use of IV glutathione and IV vitamin C to reduce the risk of viral infection and aid recovery. [17-20] A drop in glutathione levels impairs vitamin C recycling which dramatically increases the demand for vitamin C intake. Thus, a selenium deficiency may increase the risk of a severe viral infection, because it can cause deficiencies of glutathione and vitamin C, which can impair the body's ability to combat increased cellular oxidation and acidosis, and to support a robust response by immune cells. (See also "Vitamin C Levels in Critically Ill Covid-19 Patients" http://orthomolecular.org/resources/omns/v17n17.shtml )

Does this mean we should take massive amounts of selenium supplements upon testing positive? No, It means we should consume a well-balanced diet, supplementing as necessary to maintain a full supply of nutrients, including selenium (as selenium yeast or methyl-selenocysteine) to optimize our health and resistance to infectious disease. Steady moderation is a good approach with selenium (100 mcg/d) and other essential trace elements. It also means medical doctors should continue to explore the usefulness of selenite injections and similar interventions as part of the treatment of acute viral infectious disease outbreaks, and further study the usefulness of selenium and other micronutrient testing to evaluate disease susceptibility and prognosis as well as to target personalized interventions.

Does this mean vitamin D isn't important for Covid-19 prevention or treatment? No. Vitamin D, selenocysteine, and cysteine have epigenetic and functional interdependencies. [21-25] Nutrients work best as a team. With approximately a billion chemical reactions occurring each second within each of the 37 trillion cells in the human body, a broad balanced array of nutrients is continually needed to build and sustain the sophisticated functions of human life. Most of us need to take vitamin D supplements (2,000 - 10,000 IU/d) throughout the winter months to maintain a healthy vitamin D status.

To learn more:

NIACIN for COVID: How niacin, niacinamide, and NAD can help with Long COVID-19
http://orthomolecular.org/resources/omns/v18n25.shtml

Nutrition to Treat and Prevent COVID-19
http://orthomolecular.org/resources/omns/v17n03.shtml

Fueling the Immune System for the 21st Century
http://orthomolecular.org/resources/omns/v18n23.shtml

Selenium not only benefits the host constitution and defenses, but it also has positive impacts on the mutagenesis and pathogenicity of viruses. [26-27] Virus replication is unstable and allows frequent mutations. However, the viral environment influences the rate and character of these mutations. Several varieties of viruses, including influenza, enteroviruses, and coxsackie viruses, have been shown to rapidly take on more harmful characteristics when allowed to replicate in a selenium deficient environment. [28-31] Oxidative environments also increase the rate of viral mutations. [32-34] See also Viral Mutations and the Risk of Second-hand Malnutrition'" http://orthomolecular.org/resources/omns/v17n19.shtml

Whether the invader is tuberculosis, poliovirus, influenza, SARS, Zika, SARS-CoV-2, mpox, invasive streptococcus, avian influenza, Ebola, venom, or the Andromeda Strain, the wisdom of Dr. Fred Klenner applies: "The answer to these emergencies is simple. Large amounts of ascorbic acid 350 mg to 700 mg per kilogram (2.2 lb) g body weight given intravenously. . . Ascorbic acid is also given, by mouth, as followup treatment. Every emergency room should be stocked with vitamin C ampoules of sufficient strength so that time will never be counted-as a factor in saving a life. The 4 gram, 20 cc ampoule and 10 gram 50 cc ampoule must be made available to the physician." [35]

"In my department and other hospitals we highly recommend the
patients use 12,000 mg to 24,000 mg a day of vitamin C. That works
for significant reduction of COVID becoming a severe case."

(ZhiYong Peng, MD, Chief of Critical Care
Zhongnan Hospital, Wuhan University)

Vitamin C goes to work fast - it doesn't need to be incorporated into proteins before it begins to help fight the invasion and support the host. It also offers benefit to every cell in the body, helping to support the intense metabolic bursts of activated immune cells, as well as helping maintain the integrity of blood vessels. In critical illness, large doses help counteract cellular acidosis and restore enzymes to constructive rather than destructive activity. It is not blocked by the blood-brain barrier. Aside from rare instances of G6PD deficiency, vitamin C has a tremendous safety profile over a very wide therapeutic range. Glutathione, selenocysteine, vitamin D, niacin, magnesium also are key nutrients to optimizing immune responses and recovery. [36-43]

Conclusion

The threat of infectious diseases is ubiquitous. SARS-CoV-2 and many other RNA viruses have a destructive impact on selenoproteins and glutathione. Viral replication within selenium deficient, oxidative environments promotes more rapid and more pathogenic mutations. Selenium and glutathione are critical, but they are not silver bullets. Nutrients do their best work as a team. A strong base of selenium containing selenocysteine, sulfur containing cysteine, and zinc helps to optimize vitamin D, vitamin C, B vitamins, and essential lipids for overall wellness and infectious disease prevention. Four pillars of overall wellness and infectious disease protection are to: Sleep well; Exercise the body and mind well; eat well, supplementing as necessary and flexing up nutrient intake - particularly vitamin C - in proportion to the scope of infection; and cultivate a positive, grateful mindset and social support network.

(Michael Passwater, Assistant Editor of the Orthomolecular Medicine News Service, is also the author of "Protecting Against Viruses and other Threats to Wellness" http://orthomolecular.org/resources/omns/v18n30.shtml and coauthor of "Save Lives and Improve Public Health" http://orthomolecular.org/resources/omns/v19n12.shtml and "Nutrient Benefit Statements and the 2010 Legal Victory Prohibiting FDA Censorship" http://orthomolecular.org/resources/omns/v19n03.shtml . )

References and Further Reading

1. Hollowell A, Carbajal E (2023) COVID-19's toll 3 years in: 6 notes. Becker's Healthcare 3/10/2023. https://www.beckershospitalreview.com/public-health/covid-19s-toll-3-years-in-6-notes.html

2. Polonikov A. (2020) Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients. ACS Infect. Dis. 6:1558-1562. https://pubmed.ncbi.nlm.nih.gov/32463221

3. Passwater RA (2020) Can Selenium Significantly Increase the Cure Rate in COVID-19? An Interview with Professor Ethan Will Taylor. Whole Foods Magazine, June 18, 2020. https://wholefoodsmagazine.com/columns/vitamin-connection/can-selenium-signifcantly-increase-the-cure-rate-in-covid-19

4. Hiffler L, Rakotoambinina B (2020) Selenium and RNA Virus Interactions: Potential Implications for SARS-CoV-2. Infection (COVID-19). Front. Nutr. 7:164. https://pubmed.ncbi.nlm.nih.gov/33015130

5. Vavougios GD, Ntoskas KT, Doskas TK. (2020) Impairment in selenocysteine synthesis as a candidate mechanism of inducible coagulopathy in COVID-19 patients. Med Hypotheses 147:110475. https://pubmed.ncbi.nlm.nih.gov/33421689

6. Taylor EW. (2020) RNA viruses vs. DNA synthesis: a general viral strategy that may contribute to the protective antiviral effects of selenium. Preprints 2020, 10.20944/preprints202006.0069.v1, http://doi.org/10.20944/preprints202006.0069.v1

7. Taylor EW, Radding W. (2020) Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis? Front Nutr. 7:143. https://pubmed.ncbi.nlm.nih.gov/32984400

8. Holford P (2020) Vitamin C for the Prevention and Treatment of Coronavirus. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n36.shtml

9. Gonzalez MJ (2020) Personalize Your COVID-19 Prevention: An Orthomolecular Protocol. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n31.shtml

10. Rasmussen MPF (2020) Vitamin C Evidence for Treating Complications of COVID-19 and other Viral Infections. Orthomolecular Medicine News Service. http://orthomolecular.org/resources/omns/v16n25.shtml

11. Larvie DY, Perrin MT, Donati GL, Armah SM (2023) COVID-19 Severity Is Associated with Selenium Intake among Young Adults with Low Selenium and Zinc Intake in North Carolina. Curr Dev Nutr. 7:100044. https://pubmed.ncbi.nlm.nih.gov/36785737

12. Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. (2020) Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr. 111:1297-1299. https://pubmed.ncbi.nlm.nih.gov/32342979

13. Zhang et al. (2021) Association between fatality rate of COVID-19 and selenium deficiency in China BMC Infect Dis. 21:452. https://pubmed.ncbi.nlm.nih.gov/34011281

14. Moghaddam A, Heller RA, Sun Q, et al. (2020) Selenium deficiency is associated with mortality risk from COVID-19. Nutrients 12:2098. https://pubmed.ncbi.nlm.nih.gov/32708526

15. Heller RA, Sun Q, Hackler J, et al. (2021) Prediction of survival odds in COVID-19 by zinc, age, and selenoprotein P as composite biomarker. Redox Biol. 38:101764. https://pubmed.ncbi.nlm.nih.gov/33126054

16. Gallardo IA, Todd DA, Lima ST, Taylor EW, et al. (2023) SARS-CoV-2 Main Protease Targets Host Selenoproteins and Glutathione Biosynthesis for Knockdown via Proteolysis, Potentially Disrupting the Thioredoxin and Glutaredoxin Redox Cycles. Antioxidants 12:559. https://doi.org/10.3390/antiox12030559

17. Horowitz RI, Freeman PR, Bruzzese J. (2020) Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Respir Med Case Rep. 30:101063. https://pubmed.ncbi.nlm.nih.gov/32322478

18. Colunga Biancatelli RM, Berrill M, Catravas JD, Marik PE. (2020) Quercetin and Vitamin C: An experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19). Front Immunol, 11:1451. https://pubmed.ncbi.nlm.nih.gov/32636851

19. Khan HMW, Parikh N, Megah SM, Predeteanu GS. (2020) Unusual Early Recovery of a Critical COVID-19 After Administration of Intravenous Vitamin C. Am J Case Rep, 21:e925521 https://pubmed.ncbi.nlm.nih.gov/32709838

20. Wang Y, Zhao N, Xiong Y, et al. (2020) Downregulated Recycling Process but Not De Novo Synthesis of Glutathione Limits Antioxidant Capacity of Erythrocytes in Hypoxia. Oxidative Medicine and Cellular Longevity. 2020:7834252. https://pubmed.ncbi.nlm.nih.gov/32963701

21. Jain SK, Micinski D. (2013) Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun 437:7-11, https://pubmed.ncbi.nlm.nih.gov/23770363

22. Alvarez JA, Chowdhury R, Jones DP, et al. (2014) Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults. Clin Endocrinol (Oxf) 81:458-466. https://pubmed.ncbi.nlm.nih.gov/24628365

23. Parsanathan R, Jain SK. (2019) Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Sci Rep. 9:14784. https://pubmed.ncbi.nlm.nih.gov/31616013

24. Fan YG, Pang ZQ, Wu TY, et al. (2020) Vitamin D deficiency exacerbates Alzheimer-like pathologies by reducing antioxidant capacity. Free Radic Biol Med. 161:139-149. https://pubmed.ncbi.nlm.nih.gov/33068737

25. Jain SK, Parsanathan R, Achari AE, et al. (2017) Glutathione Stimulates Vitamin D Regulatory and Glucose Metabolism Genes, Lowers Oxidative Stress and Inflammation, and Increases 25-Hydroxy-Vitamin D Levels in Blood: A Novel Approach to Treat 25-Hydroxyvitamin D Deficiency. Antioxid Redox Signal. 29:1792-1807. https://pubmed.ncbi.nlm.nih.gov/30160165

26. Beck MA, Handy J, Levander OA (2004) Host nutritional status: the neglected virulence factor. Trends Microbiol 12:417-423. https://pubmed.ncbi.nlm.nih.gov/15337163

27. Beck MA (1999) Trace Minerals, Immune Function, and Viral Evolution. Chapter 16 in: Military Strategies for Sustainment of Nutrition and Immune Function in the Field. Institute of Medicine (US), Committee on Military Nutrition Research. US National Academies Press. ISBN-13: 978-0309063456 https://www.ncbi.nlm.nih.gov/books/NBK230971

28. Harthill M. (2011) Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res. 143:1325-1336. https://pubmed.ncbi.nlm.nih.gov/21318622

29. Beck MA. Kolbeck PC, Rohr LH, et al. (1994a) Benign human enterovirus becomes virulent in selenium-deficient mice. J. Med. Virol. 43:166-170. https://pubmed.ncbi.nlm.nih.gov/8083665

30. Nelson HK, Shi Q, Van Dael P. et al. (2001) Host nutritional selenium status as a driving force for influenza virus mutations. FASEB J. 15:1721-1738. https://pubmed.ncbi.nlm.nih.gov/11481250

31. Beck MA, Nelson HK, Shi Q, et al. (2001) Selenium deficiency increases the pathology of an influenza virus infection. FASEB J. 15:1481-1483. https://pubmed.ncbi.nlm.nih.gov/11387264

32. Beck MA, Levander OA. (1998) Dietary oxidative stress and the potentiation of viral infection. Annu. Rev. Nutr. 18:93-116. https://pubmed.ncbi.nlm.nih.gov/9706220

33. Akaike T, Fujii S, Kato A, et al. (2000) Viral mutation accelerated by nitric oxide production during infection in vivo. FASEB J. 14:1447-1454. https://pubmed.ncbi.nlm.nih.gov/10877838

34. Akaike TY, Noguchi, S Ijiri, et al. (1996) Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc. Natl. Acad. Sci. USA. 93:2448-2453. https://pubmed.ncbi.nlm.nih.gov/8637894

35. Klenner FR. (1971) Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of a Vitamin In Human Pathology. J Applied Nutrit. 23:61-87. https://www.injectablevitaminc.com/images/Ch22.pdf

36. Sakr Y, Reinhart K, Bloos F, et al. (2007) Time course and relationship between plasma selenium concentrations, systemic inflammatory response, sepsis, and multiorgan failure. Br J Anaesth. 98:775-784. https://pubmed.ncbi.nlm.nih.gov/17478454

37. de Melo AF, Homem-de-Mello M. (2020) High-dose intravenous vitamin C may help in cytokine storm in severe SARS-CoV-2 infection. Crit Care 24:500. https://pubmed.ncbi.nlm.nih.gov/32792018

38. Wang Y, Huang J, Sun Y, et al. (2021) SARS-CoV-2 suppresses mRNA expression of selenoproteins associated with ferroptosis, endoplasmic reticulum stress and DNA synthesis. Food Chem Toxicol. 153:112286. https://pubmed.ncbi.nlm.nih.gov/34023458

39. Guillin OM, Vindry C, Ohlmann T, Chavatte L (2019) Selenium, Selenoproteins and Viral Infection.Nutrients 11:2101. https://pubmed.ncbi.nlm.nih.gov/31487871

40. Broome CS, McArdle F, Kyle JAM, et al. (2004) An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am. J. Clin Nutr. 80:154-162. https://pubmed.ncbi.nlm.nih.gov/15213043

41. Guillin OM, Vindry C, Ohlmann T, Chavatte L. (2019) Selenium, Selenoproteins, and Viral Infection. Nutrients 11:2101. https://pubmed.ncbi.nlm.nih.gov/31487871

42. Taylor EW, Ruzicka JA, Premadasa L, Zhao L (2016) Cellular Selenoprotein mRNA Tethering via Antisense Interactions with Ebola and HIV-1 mRNAs May Impact Host Selenium Biochemistry. Cur Top Med Chem. 16:1530-1535. https://pubmed.ncbi.nlm.nih.gov/26369818

43. Beck MA, Esworthy RS, Ho YS, Chu FF (1998) Glutathione peroxidase protects mice from viral-induced myocarditis. FASEB J. 12:1143-1149. https://pubmed.ncbi.nlm.nih.gov/9737717 https://www.researchgate.net/publication/13547567_Glutathione_peroxidase_protects_mice_from_viral-induced_myocarditis

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