Should we be recommending Vitamin D and/or zinc supplementation for treatment of COVID-19 to prevent severe outcomes? 

Posted on June 1, 2020 by Raymond Cho

Summary

  • For both vitamin D and zinc, there is circumstantial evidence suggesting that supplementation improves outcomes in non-COVID-19 coronaviruses but no specific clinical evidence for COVID-19 itself.
  • Populations deficient in vitamin D (i.e. elderly, populations above latitude 35 degrees North, etc.) may be at higher risk of developing severe COVID-19. 
  • There is currently no strong evidence to support supplementation with vitamin D or zinc. There are some proponents for vitamin D supplementation especially for those who are nutrient deficient or at high risk, but there is significant debate.

I.   Evidence for Vitamin D in COVID-19

  • There is some speculation that patients with low serum vitamin D have a higher risk of infection and worse outcomes when infected with COVID-19. Much of the proposed effects of vitamin D on COVID-19 outcomes is based on previously-known data on the effects of vitamin D on other coronaviruses as well as observational data on populations at high risk of vitamin D deficiency (i.e. chronic disease, African, elderly, etc.) that does not control for confounders (1).
    • Daneshkhah et. al. (pre-print) showed that 17.3% of patients with severe vitamin D deficiency developed severe COVID-19 while 14.6% patients with normal vitamin D developed severe infection (severity based on CRP values) (2). They speculate that vitamin D may suppress cytokine storm activity.
    • Although there is no clinical evidence that vitamin D supplementation is beneficial in treating or preventing COVID-19, there is some evidence that vitamin D could prevent other acute respiratory infections. A meta-analysis showed that Vitamin D supplementation resulted in reduction of patients experiencing at least one respiratory tract infection especially in those with severe deficiencies i.e. < 25 nmol/L (NNT = 33 [20-101]) (3).
    • Ilie et. al. showed evidence that there is a potential association between serum vitamin D and mortality caused by COVID-19 (4). 
    • Rhodes et. al. in an editorial suggests that there is greater mortality in countries north of latitude 35 degrees North, which is also where patients do not receive sufficient sunlight for sufficient vitamin D levels (5).  
  • Conclusion: although there is evidence that vitamin D improves outcomes in other acute respiratory tract infections and circumstantial evidence that correlate vitamin D with COVID-19 outcomes, there is a lack of trial evidence of these findings. There are randomized clinical trials currently underway to study whether vitamin D significantly improves COVID-19 endpoints (6,7).

II.   Evidence for Zinc in COVID-19/other coronaviruses

  • The evidence for zinc is also similar to that of vitamin D; there is currently only circumstantial evidence in that zinc has been shown to improve outcomes in other coronaviruses but not in COVID-19 specifically (8).
    • A Cochrane review of 18 RCTs in 2013 shows that zinc may shorten duration of the common cold by an average of 1.03 days  when taken within 24 hours of symptom onset with a dose higher than 75 mg/day (9).
    • Velthius showed that zinc can inhibit coronavirus’ RNA synthesis pathway, which COVID-19 is thought to have a similar mechanism (10).
  • Conclusion: there is evidence that zinc can shorten the duration and inhibit viral replication of coronaviruses but no direct evidence to support this mechanism in COVID-19 specifically.

Questions? Comments? Does this need to be updated? Do you have valuable points to add ? Please email ask.reakt@ubc.ca.

References

  1. Lee J, van Hecke O, Roberts N. Vitamin D: A rapid review of the evidence for treatment or prevention in COVID-19 [Internet]. Centre for Evidence-Based Medicine. 2020 [cited 2020May10]. Available from: https://www.cebm.net/covid-19/vitamin-d-a-rapid-review-of-the-evidence-for-treatment-or-prevention-in-covid-19/
  2. Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv. 2020Apr30;
  3. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017Feb15;:i6583.
  4. Ilie PC, Stefanescu S, Smith L. The role of Vitamin D in the prevention of Coronavirus Disease 2019 infection and mortality. Aging Clinical and Experimental Research. 2020May6;
  5. Rhodes JM, Subramanian S, Laird E, Kenny RA. Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity. Alimentary Pharmacology & Therapeutics. 2020Apr20;
  6. Castillo MJ, Gahete A. Vitamin D on Prevention and Treatment of COVID-19 – Full Text View [Internet]. Vitamin D on Prevention and Treatment of COVID-19 – Full Text View – ClinicalTrials.gov. [cited 2020May10]. Available from: https://clinicaltrials.gov/ct2/show/NCT04334005
  7. Annweiler C. Covid-19 and Vitamin D Supplementation: a Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients (CoVitTrial) – Full Text View [Internet]. Full Text View – ClinicalTrials.gov. [cited 2020May10]. Available from: https://clinicaltrials.gov/ct2/show/NCT04344041
  8. Neff T. Zinc could help diminish the extent of COVID-19 [Internet]. UCHealth Today. 2020 [cited 2020May10]. Available from: https://www.uchealth.org/today/zinc-could-help-diminish-extent-of-covid-19/
  9. Singh M, Das RR. Zinc for the common cold. Cochrane Database of Systematic Reviews. 2013Jun18;
  10. Velthuis AJWT, Sjoerd H. E. Van Den Worm, Sims AC, Baric RS, Snijder EJ, Hemert MJV. Zn2 Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLoS Pathogens. 2010Nov4;6(11).

Disclaimer

The above is intended to serve as a rapidly-created, accessible source of information curated by medical students and healthcare professionals. It is for educational purposes only and is not a complete reference resource. It is not professional medical advice, and is not a substitute for the discretion, judgment, and duties of healthcare professionals. You are solely responsible for evaluating the information above.