Intended for healthcare professionals

Rapid response to:

Editorials

Vitamin D and covid-19

BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n544 (Published 04 March 2021) Cite this as: BMJ 2021;372:n544

Read our latest coverage of the coronavirus outbreak

Rapid Response:

Susceptibilities to COVID-19 severity and complications are driven largely by vitamin D deficiency

Dear Editor:

There are numerous studies that strongly suggest that susceptibilities to COVID-19 severity and complications are driven largely by vitamin D deficiency.

Jain et al found Vitamin D deficiency in 97% of severely ill patients who required ICU admission but in only 33% of asymptomatic cases, suggesting that low levels are a necessary component of severe COVID-19.[1]

De Smet et al found that Vitamin D deficiency on admission was associated with a nearly FOUR-FOLD risk of COVID-19 mortality, and specify that this is independent of age, chronic lung disease, coronary artery disease, hypertension, or diabetes. [2]

Those findings are all the more remarkable considering that vitamin D deficiency is also strongly associated with increased age, chronic lung disease, asthma, coronary artery disease, blood clotting disorders, hypertension, types 1 AND 2 diabetes, obesity, even exposure to tobacco smoke,-- all known as signficant susceptibilities to COVID-19 severity and complications. [3] - [18]

It’s also worth noting that the first two COVID-19 outbreak epicenters were in Wuhan, China and Milan, Italy, both with well-known high levels of air pollution and resulting lung issues in inhabitants. Multiple studies have documented strong correlation between air pollution exposure and vitamin D deficiency. [19] [20] [21]

Don’t all of these astonishing parallels indicate that far earlier addressing of vitamin D deficiency is called for than that used in the study protocol for the Sao Paulo, Brazil trial cited by Vimaleswaren, Forouhi, and Khunti?
[22] The study protocol used there seems awfully illogical: rather than being given the treatment at diagnosis, it was at a mean of 10.4 days after onset of symptoms that patients were given a single enormous dose of vitamin D — 200,000 IU dissolved in 10 mL of peanut oil (I’m not sure I would keep that down, and I’m not even sick) — rather than lower daily doses, as other studies with successful outcomes did. 

Could such a high single dose have caused hypercalcemia and increased the mortality rate of the test group? And if so, for which individuals/susceptibilties?



It also seems curious that absolute risk reduction rather than relative risk reduction was noted, when vaccine efficacy testing always uses relative risk reduction.



Further study is always a good call, but given the staggering correlations between vitamin D deficiency and every known susceptibility to COVID-19 severity and complications, doesn’t it do more harm than good to withhold addressing the widespread vitamin D deficiency that is putting citizens of every country at grave risk?



References
1. Jain, A., Chaurasia, R., Sengar, N.S. et al. Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep 10, 20191 (2020). https://doi.org/10.1038/s41598-020-77093-z

2. Dieter De Smet, MD, Kristof De Smet, MD, Pauline Herroelen, MSc, Stefaan Gryspeerdt, MD, Geert A Martens, MD, PhD, Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality, American Journal of Clinical Pathology, Volume 155, Issue 3, March 2021, Pages 381–388, https://doi.org/10.1093/ajcp/aqaa252

3. Kweder H, Eidi H. Vitamin D deficiency in elderly: Risk factors and drugs impact on vitamin D status. Avicenna J Med. 2018;8(4): 139-146. Dos:10.4103/ajm.AJM_20_18

4. Boucher B; The Problems of Vitamin D Insufficiency in Older People. Aging Dis. 2012 3(4): 313– 329

5. Martineau A et al; Vitamin D reduces lung disease flare-ups by over 40 percent The Lancet Respiratory Medicine, 2014; DOI: 10.1016/S2213-2600(14)70255-3

6. Gilbert CR, Arum SM, Smith CM. Vitamin D deficiency and chronic lung disease. Can Respir J. 2009; 16(3):75-80. Doi:10.1155/2009/829130

7. Kelly A, Sen C. Is Vitamin D Deficiency the Root of All Pulmonary Evils? Ann Am Thorac Soc. 2014 Feb;11(2):220-2. doi: 10.1513/AnnalsATS.201401-009ED. PMID: 24575988issue 2

8. Martineau  AR, Cates  CJ, Urashima  M, Jensen  M, Griffiths  AP, Nurmatov  U, Sheikh  A, Griffiths  CJ. Vitamin D for the management of asthma. Cochrane Database of Systematic Reviews 2016, Issue 9. Art. No.: CD011511. DOI: 10.1002/14651858.CD011511.pub2. Accessed 06 March 2021.

9. Dhibar DP, Sharma YP, Bhadada SK, Sachdeva N, Sahu KK. Association of Vitamin D Deficiency with Coronary Artery Disease. J. Clin Diagn Res. 2016;10(9):OC24-OC28. Dos:10.7860/JCDR/2016/227188526

10. Khademvatani K, Seyyed-Mohammadzad MH, Akbari M, Rezaei Y, Eskandari R, Rostamzadeeh A; The relationship between vitamin D status and idiopathic lower-extremity deep vein thrombosis Int J Gen Med. 2014;7:303-309. Published 2014 Jun 19. doi:10.2147/IJGM.S64812

11. Mehta V, Agarwal S. Does Vitamin D Deficiency Lead to Hypertension?. Cureus. 2017;9(2):e1038. Published 2017 Feb 17. doi:10.7759/cureus.1038

12. C Michos, ED Do lower vitamin D levels mean higher risk for cardiovascular disease?
https://www.hopkinsmedicine.org/health/wellness-and-prevention/vitamin-d...

13. Vimaleswaran KS, Cavadino A, Berry DJ; LifeLines Cohort Study investigators, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014 Sep;2(9):719-29. doi: 10.1016/S2213-8587(14)70113-5. Epub 2014 Jun 25. PMID: 24974252; PMCID: PMC4582411.

14. Schwalfenberg, G; Vitamin D and diabetes: improvement of glycemic control with vitamin D3 repletion. Can Fam Physician. 2008;54(6):864-866.

15. Jacobo Wortsman, Lois Y Matsuoka, Tai C Chen, Zhiren Lu, Michael F Holick, Decreased bioavailability of vitamin D in obesity, The American Journal of Clinical Nutrition, Volume 72, Issue 3, September 2000, Pages 690–693, https://doi.org/10.1093/ajcn/72.3.690

16. Vimaleswaran KS, Berry DJ, Lu C, et al. Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10(2):e1001383. doi:10.1371/journal.pmed.1001383

17. Zakharova I, Klimov L, Kuryaninova V, et al. Vitamin D Insufficiency in Overweight and Obese Children and Adolescents. Front Endocrinol (Lausanne). 2019;10:103. Published 2019 Mar 1. doi:10.3389/fendo.2019.00103

18. Nwosu BU, Kum-Nji P. Tobacco smoke exposure is an independent predictor of vitamin D deficiency in US children. PLoS One. 2018 Oct 8;13(10):e0205342. doi: 10.1371/journal.pone.0205342. PMID: 30296288; PMCID: PMC6175516.

19. Agarwal KS, Mughal MZ, Upadhyay P, et al The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India Archives of Disease in Childhood 2002;87:111-113.

20. Hosseinpanah F, Pour SH, Heibatollahi M, Moghbel N, Asefzade S, Azizi F. The effects of air pollution on vitamin D status in healthy women: a cross sectional study. BMC Public Health. 2010;10:519. Published 2010 Aug 29. doi:10.1186/1471-2458-10-519

21. Hoseinzadeh E, Taha P, Wei C, Godini H, Ashraf GM, Taghavi M, Miri M. The impact of air pollutants, UV exposure and geographic location on vitamin D deficiency. Food Chem Toxicol. 2018 Mar;113:241-254. doi: 10.1016/j.fct.2018.01.052. Epub 2018 Feb 1. PMID: 29409825.

22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe covid-19: a randomized clinical trial. JAMA2021. doi:10.1001/jama.2020.26848. PMID:33595634

Competing interests: No competing interests

06 March 2021
Alison B Fujito
Violinist
Pittsburgh Symphony Orchestra
Pittsburgh, PA