Maurizio Rossini

Department of Medicine, Section of Rheumatology, University of Verona

Because of this accursed and seemingly never-ending SARS-CoV-2 pandemic, we felt it our duty to devote this entire issue of the journal to an update on the possible role of vitamin D deficiency and its supplementation on the risk of COVID-19. Moreover, the scientific work product on this topic continues to abound, to such an extent that a dedicated bibliography selection became necessary for this issue as well.

It is interesting to note how the prestigious authors entrusted with the task of issuing an update on the relationship between vitamin D, immunity, inflammation, and especially on the risk of falling ill with COVID-19, have reached the same honestly cautious conclusions, albeit with broadly differing motivations and supporting arguments:

• “Considering the volume and significance of the findings accumulated so far, several double-blind, randomised controlled trials have been initiated and are under way… Therefore, it is frankly possible that in a reasonably short time the role of vitamin D, and of cholecalciferol specifically, as a possible medicine to help fight the SARS-CoV-2 pandemic could be confirmed”;

• “There are copious indications that vitamin D may exert effective protective action through modulation of the immunological response, attenuation of the cytokine storm and the inflammatory response, preservation of the integrity of the pulmonary epithelial barrier and through its antithrombotic action… Nevertheless, conclusive findings on the effects of supplementation in COVID-19 patients are not yet available. This is because, although they tend to show a favourable effect overall, results from the several observational studies and the few clinical trials available today have not been unambiguous. The discrepancies among the different studies can be explained on the basis of… Clearly there is a need to wait for the results of the additional trials currently in progress…”.

In light of this, in my opinion, the following statement reiterated in the recent Ministry of Health Circular on home management of patients infected with SARS‑CoV-2, updated on 26 April 2021, appears to be understandable and acceptable [1]: “It should be noted that, to date, there are no solid and incontrovertible findings (i.e., drawn from controlled clinical trials) demonstrating the effectiveness of vitamins and food supplements (e.g., vitamins, including vitamin D, lactoferrin, quercetin)…”.

On the other hand, I do believe that the following conclusion may be revised… or better supported in the near future: “… the use of which for this indication is therefore not recommended”. I understand our Ministry’s concern that it not promote supposed protective interventions, which in reality cannot guarantee protection from SARS-CoV-2 with any degree of certainty, and which may perhaps falsely induce imprudent behaviour which ignores established precautionary measures that do indeed reduce the risk of infection.

I do believe, nonetheless, that the conclusion could be misinterpreted as a recommendation to not use. I think that one can only recommend not to use that which may involve health risks or which has solid and incontrovertible evidence of inefficacy. I do not think that this currently applies to vitamin D supplementation in deficient subjects, given:

• the physiological-immunomodulatory role of vitamin D, also acknowledged by AIFA, the Italian Medicines Agency, in its background to Note 96;

• the presumed pathophysiological involvement of vitamin D; 

• the results of many observational studies indicating a possible association between hypovitaminosis D and the risk of becoming infected by SARS‑CoV-2 or seriously ill with COVID-19;

• the strong rationale and the widely acknowledged need for specific clinical trials on vitamin D supplementation, as recently concluded in a dedicated Cochrane review [2].

It seems to me that all this generates at least a reasonable doubt that today, vitamin D’s contribution to preventing the risk of contracting the COVID-19 infection and/or its more severe clinical manifestations should not be ruled out.

I would also like to point out that among the Ministry of Health’s Fake News reports, along with, for example, the item according to which “applying Vaseline or other creams around the nostrils traps the virus so that it cannot enter the nose”, there is still the item published on 9 April 2020 [3], which asserts that “vitamin D protects against infection by the novel coronavirus”. At the time, that item’s classification as a hoax might have been justified because that statement could have given rise to hazardous illusions, given that, at the time, there was not enough scientific evidence that vitamin D could play a role in protection against the virus. However, can we still be certain of that today? Would it not be wise to now exclude such an assertion from the hoaxes while awaiting the imminent results of controlled clinical trials? This since there is now current scientific evidence that vitamin D does indeed play a role in protecting against infection by the novel coronavirus or at least against some of its more serious manifestations.

After reading the two articles and the specific selected bibliography in this issue, it will be interesting to see what you think about these points.

Happy reading and take care.

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