SARS-CoV-2 morbidity depending on vitamin D status

BACKGROUND: The association between vitamin D deficiency and the severity of COVID-19 is currently being actively discussed around the world.
AIM: The aim of this study was to assess the prevalence of vitamin D insufficiency and deficiency and compare it with the incidence rates of SARS-CoV-2 in eight Federal Districts of the Russian Federation.
MATERIALS AND METHODS: We included 304,564 patients (234,716 women; 77,1%) with serum 25(OH)D levels results performed September 2019 through October 2020.
RESULTS: Only 112,877 people (37.1%) had a normal serum 25(OH)D level, others had a deficiency. Vitamin D insufficiency and deficiency was presented with the same frequency in women and men, and no differences were found depending on the geographical location and age in subjects from 18 to 74 years old. However, subjects over 75 years more often had vitamin D deficiency, while subjects under 18 years had normal levels in over 50% cases. In addition, 21,506 patients were tested for SARS-CoV-2 by PCR with further comparison of results with serum 25(OH)D level. The SARS-CoV-2 positivity rate was detected in 3,193 subjects, negative in 18,313. There were no differences in the morbidity in a vitamin D deficiency and a normal level. Thus, 14.8% subjects had positive PCR rates among vitamin D deficiency patients (4,978 tests), 14.9% when 25(OD)D level was from 20 to 30 ng/ml (7,542 tests), 15.0% among those who had 25(OH)D 30- 50 ng/ml (6,622 tests), and 13.9% when vitamin D was more than 50 ng/ml (4,612 tests).
CONCLUSION: There was no association between the COVID-19 incidence and vitamin D status in different regions of Russia. Although the nutrient deficiency persists in all regions and is most often diagnosed in people over 75 years old.

1. Cashman KD, Van den Heuvel EG, Schoemaker RJ, et al. 25-Hydroxyvitamin D as a Biomarker of Vitamin D Status and Its Modeling to Inform Strategies for Prevention of Vitamin D Deficiency within the Population. Adv Nutr. 2017;8(6):947-957. doi:10.3945/an.117.015578.

2. Cashman KD, Dowling KG, Škrabáková Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016;103(4):1033-1044. doi: https://doi.org/10.3945/ajcn.115.120873.

3. Hilger J, Friedel A, Herr R, et al. A systematic review of vitamin D status in populations worldwide. Br J Nutr. 2014;111(1):23-45. doi: https://doi.org/10.1017/S0007114513001840.

4. Karonova TL, Grineva EN, Nikitina IL, et al. The prevalence of vitamin D deficiency in the Northwestern region of the Russian Federation among the residents of St. Petersburg and Petrozavodsk Osteoporoz i osteopatii. 2013;3:3-7 (In Russ.). doi: https://doi.org/10.14341/osteo201333

5. Suplotova LA, Avdeeva VA, Rozhinskaja LJa, et al. Analiz faktorov riska deficita vitamina D po rezul’tatam pervogo jetapa rossijskogo neintervencionnogo registrovogo issledovanija. Medicinskij sovet. 2021;(7):21-31 (In Russ.). https://doi.org/10.21518/2079-701X-2021-7-109-118

6. Karonova TL, Golovatyuk KA, Andreeva AT, Vashukova MA, et al. Jendokrinnaja Sistema, vitamin-gormon D i COVID-19. Terapija. 2020;8:152-159. (In Russ.). doi: https://dx.doi.org/10.18565/therapy.2020.8.XX-XX

7. Karonova TL, Andreeva AT, Vashukova MA. Uroven’ 25(ON)D v syvorotke krovi u bol’nyh COVID-19. Zhurnal infektologii. 2020;12(3). (In Russ.). https://doi.org/10.22625/2072-6732-2020-12-3-21-27

8. Karonova TL, Vashukova MA, Gusev DA, et al. Vitamin D kak faktor povyshenija immuniteta i snizhenija riska razvitija ostryh respiratornyh virusnyh infekcij i COVID-19. Arterial’naja gipertenzija. 2020;26(3):295-303. (In Russ.). https://doi.org/10.18705/1607-419X-2020-26-3-295-303

9. Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID- 19 infections and deaths. Nutrients. 2020;12(4):988. doi: https://doi.org/10.3390/nu12040988.

10. Pubmed.ncbi.nlm.nih.gov. [Internet]. National library of medicine. [updated 2021 May 1; cited 2021 May 1]. Available from: https://pubmed.ncbi.nlm.nih.gov/

11. Hewison M, Freeman L, Hughes S, et al. Differential regulation of vitamin D receptor and its ligand in human monocyte- derived dendritic cells. J Immunol. 2003;170(11):5382-5390. doi: https://doi.org/10.4049/jimmunol.170.11.5382.

12. Ginde A, Mansbach J, Camargo C. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384-90. doi: https://doi.org/10.1001/archinternmed.2008.560

13. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770-1773. doi: https://doi.org/10.1126/science.1123933.

14. Adams JS, Ren S, Liu PT, et al. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009;82(7):4289-4295. doi: https://doi.org/10.4049/jimmunol.0803736.

15. Agier J, Efenberger M, Brzezinska-Blaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol. 2015;40(2):225-235. doi: https://doi.org/10.5114/ceji.2015.51359.

16. Kaufman HW, Niles JK, Kroll MH, et al. SARS- CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS ONE. 2020:15(9):e0239252. doi: https://doi.org/10.1371/journal.pone.0239252.

17. Pizzini A, Aichner M, Sahanic S, et al. Impact of Vitamin D Deficiency on COVID-19-A Prospective Analysis from the CovILD Registry. Nutrients. 2020;12(9):2775. doi: https://doi.org/10.3390/nu12092775.

18. Ling SF, Broad E, Murphy R, et al. High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study. Nutrients. 2020;12(12):3799. doi: https://doi.org/10.3390/nu12123799.

19. rosstat.gov.ru [интернет]. Федеральная служба государственной статистики [доступ от 25.02.2021]. Доступно по ссылке https://rosstat.gov.ru.

20. стопкорановирус.рф [интернет]. Коронавирус COVID-19: официальная информация. [доступ от 25.02.2021]. Доступно по ссылке https://stopkoranovirus.rf

21. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-733. doi: https://doi.org/10.1056/NEJMoa2001017.

22. Vremennye metodicheskie rekomendacii: diagnostika, profilaktika koronavirusnoj novoj lechenie i infekcii COVID-19. Ministerstvo zdravoohraneniya Rossijskoj Federacii. 11 versiya (07.05.2021). (In Russ.).

23. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. doi: https://doi.org/10.1016/S0140-6736(20)30183-5.

24. Grasselli G, Greco M, Zanella A, et al. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in Lombardy, Italy. JAMA Intern Med. 2020;180(10):1345-1355. doi: https://doi.org/10.1001/jamainternmed.2020.3539.

25. Pham H, Rahman A, Majidi A, et al. Acute respiratory tract infection and 25-hydroxyvitamin D concentration: a systematic review and meta-analysis. Int J Environ Res Public Health. 2019;16(17):3020. doi: https://doi.org/10.3390/ijerph16173020.

26. Zhou J, Du J, Huang L, et al. Preventive effects of vitamin D on seasonal influenza a in infants: a multicenter, randomized, open, controlled clinical trial. Pediatr Infect Dis J. 2018;37(8):749-754. doi: https://doi.org/10.1097/INF.0000000000001890.

27. Kroll MH, Bi C. Garber CC, et al. Temporal relationship between vitamin D status and parathyroid hormone in the United States. PLoS ONE. 2015;10(3):e0118108. doi: https://doi.org/10.1371/journal.pone.0118108.

28. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. doi: https://doi.org/10.1001/jama.2020.1585.

29. Zhou F. Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi: https://doi.org/10.1016/S0140-6736(20)30566-3.

30. Carpagnano GE, Di Lecce V, Quaranta VN, et al. Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest. 2021;44(4):765-771. doi: https://doi.org/10.1007/s40618-020-01370-x.

31. Macaya F, Paeres CE, Valls A, et al. Interaction between age and vitamin D deficiency in severe COVID-19 infection. Nutricion Hospitalaria. 2020;37(5):1039-1042. doi: https://doi.org/10.20960/nh.03193.

32. Ye K, Tang F, Liao X, et al. Does serum vitamin D level affect COVID-19 infection and its severity? A case-control study. J Am Coll Nutr. 2020;13:1-8. doi: https://doi.org/10.1080/07315724.2020.1826005.

33. Petrushkina AA, Pigarova EA, Rozhinskaya LY. The prevalence of vitamin D deficiency in Russian Federation. Osteoporoz i osteopatii. 2018;3:15-20. (In Russ.). doi: https://doi.org/10.14341/osteo10038.