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Translation of a-t 2020; 51: 84-5
 

THERAPY FROM A CRITICAL VIEWPOINT

Vitamin D against COVID-19?

The indications claimed for vitamin D have been increasing for several years (see a t 2014; 45: 22-3, 2018; 49: 94-5, 103 and others). The vitamin is now being touted as an option for the prevention and treatment of SARS-CoV-2 infections and serious cases of COVID-19 (e.g. 1). The background to this is on the one hand predominantly small observational studies investigating the possible links between the vitamin D level and COVID-19. They mostly describe associations between low levels and more frequent SARS-CoV-2 infections, severe course or increased mortality (e.g. 2, 3), but cannot be considered as evidence of a benefit due to their study design. On the other hand, randomised studies are cited, according to which vitamin D is purported to reduce the risk of acute respiratory tract infections. In 2017, we rated evidence on this issue at best as hypothesis-generating on the basis of a large meta-analysis (4) of individual patient data (a t 2017; 48: 30). A current review (5) by the British Scientific Advisory Committee on Nutrition (SACN) which is also taking into account five more recent placebo comparisons (e.g. 6) is also not finding sufficient evidence of a benefit in the general population. In any case, these data cannot necessarily be transferred to SARS-CoV-2 infections (5).

We identified a total of three published randomised studies specifically on vitamin D in patients with COVID-19: One Spanish pilot study confusingly designated both "open" and "double-masked" (7) includes 76 hospitalised patients with SARS-CoV-2 infections who were initially not treated in intensive care. According to the authors, at the time of the study they were receiving the "best available therapy", including azithromycin (ZITHROMAX, generics) and hydroxychloroquine (QUENSYL, generics), which has now been proven to be useless (e.g. e a t 6/2020c). Two thirds of the patients are also being treated with the vitamin D derivative calcifediol (DEDROGYL).* The effect is unusually strong: 1 in 50 patients (2%) receiving vitamin D had to be admitted to the intensive care unit compared to 13 out of 26 (50%) in the control group (primary endpoint) (7). There is a high risk of bias, however, among other things since the control group included more patients (48% compared to 62%) with at least one risk factor for severe progression such as diabetes and hypertension, and since no placebo was used the decision to admit the patient for intensive care was made in the knowledge of their allocation to the study arms. The study is also not suitable as evidence of a benefit in any case due to its small size. A placebo-controlled Indian study (8) of 40 people infected with SARS-CoV-2 with mild or no symptoms and a simultaneously low vitamin D level (< 20 ng/ml 25-hydroxycholecalciferol [25(OH)D]) primarily investigated the percentage of patients in whom no virus RNA was able to be identified using PCR in a throat swab after three weeks. Here, high doses of vitamin D3 (60,000 IU administered per os once daily for 7 to 14 days**) as an addition to standard treatment did better (63% vs. 21%) (8). The clinical relevance of the surrogate parameter investigated, however, is not clear (see e a t 4/2020b). There is no information on blinding.

* 0.532 mg on the day of admission followed by 0.266 mg on days 3 and 7 and subsequently once a week until the patient was discharged or transferred to the intensive care ward.
** Patients with a 25 (OH) D level > 50 ng/ml after 7 days subsequently received 60,000 IE per week, patients with lower levels 60,000 IE per day for another 7 days.

In a placebo-controlled, double-blind study (9) from Brazil just published as a preprint including 240 patients with severe COVID-19 initially not treated in intensive care, the one-off administration of 200,000 IU of vitamin D3 per os did neither have a significant impact on the length of stay in hospital (primary endpoint) nor on the mortality, need for intensive care treatment nor artificial respiration.

We currently do not see sufficient evidence of a benefit of vitamin D or vitamin D derivatives to prevent or treat a SARS-CoV-2 infection.

 (R = randomized study, M = meta-analysis)
1BENSKIN, L.L.: Front. Public Health 2020; 8: 513 (25 pages)
2ABRISHAMI, A. et al.: Eur. J. Nutr.; online publication on 30 October 2020; doi: 10.1007/s00394-020-02411-0 (9 pages)
3KAUFMAN, H.W. et al.: PLOS One 2020; 15: e0239252 (10 pages)
M  4MARTINEAU, A.R. et al.: BMJ 2017; 356: i6583 (17 pages)
5Scientific Advisory Committee on Nutrition (SACN): Rapid Review: Vitamin D and acute respiratory tract infections, June 2020; http://www.a-turl.de/?k=elve
6CAMARGO, C.A. et al.: Clin. Infect. Dis. 2020; 71: 311-7
R  7ENTRENAS CASTILLO, M. et al.: J. Steroid Biochem. Mol. Biol. 2020; 203: 105751 (6 pages)
R  8RASTOGI, A. et al.: Postgrad. Med. J.; online publication on 12 November 2020; doi: 10.1136/postgradmedj-2020-139065 (4 pages)
9MURAI, I.H. et al.: medRXIV, online publication on 17 November 2020; https://doi.org/10.1101/2020.11.16.20232397 (34 pages)

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