Response to Letter to the Editor from Viola Viola: “Calcifediol treatment and COVID-
19-related outcomes”

Xavier Nogues, José Manuel Quesada-Gómez, and Natalia Garcia-Giralt




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© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All
rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Disclosure Statement: XN has received fees from lectures and consultancy from Amgen, UCB, and

Lilly. JMQG has received small lecture or consultancy fees from Amgen and Faes Farma (Spain).

NGG has nothing to declare.




We thank Dr. Viola and colleagues for their letter to our article (1). We agree with the authors' point
that 25(OH)D levels should be assayed during the hospital stay and even after discharge.
Unfortunately, because of the harsh working conditions during the first wave of the pandemic, data




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were obtained in only a few patients. However, a rapid rise in 25(OH)D levels was expected after




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acute oral calcifediol intake, according to previous studies (2), and was confirmed in in-house controls
(data not shown). Vitamin D’s role in immune response mechanisms appears to be regulated primarily




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by availability of 25(OH)D, induction of CYP27B1 in the antigen-presenting cells by the invading
pathogens and, ultimately, by stimulation of 1,25(OH) 2D in the immune system (3). Potential effects of




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1,25(OH)2D by inducing antimicrobial peptides, recruitment of neutrophils, monocytes/macrophages,
and dendritic cells, as well as by modulating the adaptive immune response would help to overcome
the COVID-19. Importantly, vitamin D may suppress the cytokine storm by simultaneously enhancing
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the innate immune system and reducing the overactivation of the adaptive immune system (3).
Hence, treatment with calcifediol at higher doses is recommended to prevent worse COVID-19
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outcomes as an adjuvant therapy in the hospital. Anyhow, further studies in an RCT setting are being
carried out to corroborate this calcifediol effect.
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Overall, there is well-establish agreement that an adequate vitamin D status is necessary to maintain
both musculoskeletal and general health (4, 5), thus regular monitoring of 25(OH)D levels should be
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considered at the population level and, in particular, in osteoporotic patients and the elderly.
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Accordingly, calcifediol or vitamin D supplementation should be strongly recommended to maintain
adequate serum 25(OH)D levels in the general population.
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References

   1. Viola V, Leanza G and Tramontana F. Letter to the Editor from Viola Viola: “Calcifediol
       treatment and COVID-19-related outcomes”. J Clin Endocrinol Metab 2021.
   2. Quesada-Gomez JM, Bouillon R. Is calcifediol better than cholecalciferol for vitamin D
       supplementation? Osteoporos Int. 2018 Aug;29(8):1697-1711. doi: 10.1007/s00198-018-
       4520-y. Epub 2018 Apr 30. PMID: 29713796.
   3. Bilezikian JP, Bikle D, Hewison M, et al. MECHANISMS IN ENDOCRINOLOGY: Vitamin D
       and COVID-19. Eur J Endocrinol. 2020 Nov;183(5):R133-R147. doi: 10.1530/EJE-20-0665.
       PMID: 32755992.
   4. Fan X, Wang J, Song M, Giovannucci EL, et al. Vitamin D Status and Risk of All-Cause and




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       Cause-Specific Mortality in a Large Cohort: Results From the UK Biobank. J Clin Endocrinol
       Metab. 2020 Oct 1;105(10):dgaa432. doi: 10.1210/clinem/dgaa432. PMID: 32620963.




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   5. Giustina A, Adler RA, Binkley N, et al. Controversies in Vitamin D: Summary Statement From
       an International Conference. J Clin Endocrinol Metab. 2019 Feb 1;104(2):234-240. doi:




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       10.1210/jc.2018-01414. PMID: 30383226.
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