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Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation

Castle et al., Journal of Inflammation Research, doi:10.2147/JIR.S323356

Sep 2021

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Vitamin D for COVID-19

8th treatment shown to reduce risk in October 2020

^*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19early.org

Review of the effects of COVID-19 on inflammatory markers, and the effects on those markers of standard treatments vs. vitamin D, melatonin, and meditation, showing comparable or superior effects with the non-standard treatments. The standard treatments in this study were remdesivir and tocilizumab. We note that standard treatments vary widely around the world, for example vitamin D is a standard treatment in many locations.

Reviews covering vitamin D for COVID-19 include Andrade, Arora, Basha, Brenner, Cannell, DiGuilio, EFSA, EFSA (B), Foshati, Gotelli, Grant, Grant (B), Grant (C), Kohlmeier, McCullough, Mercola, Nicoll, Palacios, Quesada-Gomez, Schloss, Shah Alam, Xu.

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Study covers melatonin and vitamin D.

1. Andrade et al., Vitamin A and D deficiencies in the prognosis of respiratory tract infections: A systematic review with perspectives for COVID-19 and a critical analysis on supplementation, SciELO preprints, doi:10.1590/SciELOPreprints.839.scielo.org, doi.org.

2. Arora et al., Global Dietary and Herbal Supplement Use during COVID-19—A Scoping Review, Nutrients, doi:10.3390/nu15030771.mdpi.com, doi.org.

3. Basha et al., Is the shielding effect of cholecalciferol in SARS CoV-2 infection dependable? An evidence based unraveling, Clinical Epidemiology and Global Health, doi:10.1016/j.cegh.2020.10.005.sciencedirect.com, doi.org.

4. Brenner, H., Vitamin D Supplementation to Prevent COVID-19 Infections and Deaths—Accumulating Evidence from Epidemiological and Intervention Studies Calls for Immediate Action, Nutrients, doi:10.3390/nu13020411.mdpi.com, doi.org.

5. Cannell et al., Epidemic influenza and vitamin D, Epidemiol Infect., 2006, 134:6. 1129-40, doi:10.1017/S0950268806007175.nih.gov, doi.org.

6. DiGuilio et al., Micronutrient Improvement of Epithelial Barrier Function in Various Disease States: A Case for Adjuvant Therapy, International Journal of Molecular Sciences, doi:10.3390/ijms23062995.mdpi.com, doi.org.

7. EFSA, Scientific Opinion on the substantiation of health claims related to vitamin D and normal function of the immune system and inflammatory response (ID 154, 159), maintenance of normal muscle function (ID 155) and maintenance of normal cardiovascular function (ID 159) pursuant to Article 13(1) of Regulation (E, EFSA Journal, doi:10.2903/j.efsa.2010.1468.wiley.com, doi.org.

8. EFSA (B), Scientific Opinion on the substantiation of a health claim related to vitamin D and contribution to the normal function of the immune system pursuant to Article 14 of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2015.4096.europa.eu, doi.org.

9. Foshati et al., Antioxidants and clinical outcomes of patients with coronavirus disease 2019: A systematic review of observational and interventional studies, Food Science & Nutrition, doi:10.1002/fsn3.3034.wiley.com, doi.org.

10. Gotelli et al., Understanding the immune-endocrine effects of vitamin D in SARS-CoV-2 infection: a role in protecting against neurodamage?, Neuroimmunomodulation, doi:10.1159/000533286.karger.com, doi.org.

11. Grant, W., Vitamin D and viral infections: Infectious diseases, autoimmune diseases, and cancers, Advances in Food and Nutrition Research, doi:10.1016/bs.afnr.2023.12.007.sciencedirect.com, doi.org.

12. Grant (B) et al., A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health, Nutrients, doi:10.3390/nu14030639.mdpi.com, doi.org.

13. Grant (C) et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients, 12:4, 988, doi:10.3390/nu12040988.mdpi.com, doi.org.

14. Kohlmeier et al., When Mendelian randomisation fails, BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000265.bmj.com, doi.org.

15. McCullough et al., Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience, The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2018.12.010.sciencedirect.com, doi.org.

16. Mercola et al., Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity, Nutrients 2020, 12:11, 3361, doi:10.3390/nu12113361.mdpi.com, doi.org.

17. Nicoll et al., COVID-19 Prevention: Vitamin D Is Still a Valid Remedy, Journal of Clinical Medicine, doi:10.3390/jcm11226818.mdpi.com, doi.org.

18. Palacios et al., Is vitamin D deficiency a major global public health problem?, J Steroid Biochem Mol Biol., 2014, 144PA, 138–145, doi:10.1016/j.jsbmb.2013.11.003.nih.gov, doi.org.

19. Quesada-Gomez et al., Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol, Nutrients, doi:10.3390/nu14132716.mdpi.com, doi.org.

20. Schloss et al., Nutritional deficiencies that may predispose to long COVID, Inflammopharmacology, doi:10.1007/s10787-023-01183-3.springer.com, doi.org.

21. Shah Alam et al., The role of vitamin D in reducing SARS-CoV-2 infection: An update, International Immunopharmacology, doi:10.1016/j.intimp.2021.107686.sciencedirect.com, doi.org.

22. Xu et al., The importance of vitamin d metabolism as a potential prophylactic, immunoregulatory and neuroprotective treatment for COVID-19, Journal of Translational Medicine, doi:10.1186/s12967-020-02488-5.biomedcentral.com, doi.org.

Castle et al., 22 Sep 2021, peer-reviewed, 8 authors.

This Paper Vitamin D All

Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation

Ryan D Castle, Michelle A Williams, William C Bushell, J Adam Rindfleisch, Christine Tara Peterson, James Marzolf, Kimberly Brouwer, Paul J Mills

Journal of Inflammation Research, doi:10.2147/jir.s323356

Introduction: COVID-19 poses a chronic threat to inflammatory systems, reinforcing the need for efficient anti-inflammatory strategies. The purpose of this review and analysis was to determine the efficacy of various interventions upon the inflammatory markers most affected by COVID-19. The focus was on the markers associated with COVID-19, not the etiology of the virus itself. Methods: Based on 27 reviewed papers, information was extracted on the effects of COVID-19 upon inflammatory markers, then the effects of standard treatments (Remdesivir, Tocilizumab) and adjunctive interventions (vitamin D 3 , melatonin, and meditation) were extracted for those markers. These data were used to approximate effect sizes for the disease or interventions via standardized mean differences (SMD). Results: The data that were available indicated that adjunctive interventions affected 68.4% of the inflammatory markers impacted by COVID-19, while standard pharmaceutical medication affected 26.3%. Discussion: Nonstandard adjunctive care appeared to have comparable or superior effects in comparison to Remdesivir and Tocilizumab on the inflammatory markers most impacted by COVID-19. Alongside standards of care, melatonin, vitamin D 3 , and meditation should be considered for treatment of SARS-COV-2 infection and COVID-19 disease.

Disclosure The authors report no conflicts of interest for this work. Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/2i2QG5lT0JI Journal of Inflammation Research Dovepress

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