Increased risk for Covid-19 in patients with Vitamin D deficiency.

To the Editor:

We greatly appreciate the comments raised by Speeckaert and Delanghe that recommend including data on polymorphism of vitamin D binding protein (DBP) as a potential risk factor in patients with lower levels of vitamin D, in addition to other comorbidities such as obesity, diabetes, and cardiovascular and respiratory diseases. All are known risk factors associated with severity and mortality related to coronavirus disease 2019 (COVID-19) infection [1].

Speeckaert and Delanghe's work has demonstrated worse outcomes in people with COVID-19 and vitamin D deficiency who are carriers of the DBP2 haplotype [2]. They should be commended for their research, as it may fit into the notion of “personal medicine” and potentially account for the racial differences associated with vitamin D deficiency and morbidity related to COVID-19.

In a previous study in which black Americans were compared with white Americans, black participants had lower levels of total 25-hydroxyvitamin D and DBP but had a similar concentration of estimated bioavailable 25-hydroxyvitamin D [3]. The authors concluded that “racial differences in the prevalence of common genetic polymorphisms may provide a likely explanation for this observation.”

Although the “free hormone hypothesis” stipulates that only free and unbound vitamin D can make a cellular entry, there is some evidence that DBP-bound vitamin D can signal through some cells as well [4]. Vitamin D binding protein is genetically very polymorphic, with three frequent alleles (DBP/GC 1f, 1s, and 2) but more than 120 different variants, whose health effects are far from completely understood. In addition, there is no standardization of the polymorphism assays [4]. When DBP assays were validated by mass spectrometric methods that are considered more sensitive and specific than immunoassays for quantifying proteins in human samples, DBG levels did not vary by race, counter to prior observations by immunoassay [5].

Although the use of pharmacogenomics in research is completely justified, especially in the face of a pandemic, the lack of detailed information on DBP biological activity and the lack of prospective longitudinal studies may hinder the use of these data for the clinical care of people with COVID-19.

It seems that DBP polymorphism assays at this time may fit into an elective care framework when vitamin D deficiency is investigated and treated properly. It is premature to introduce this concept into an acute care and intensive care unit hospital setup where vitamin D is not the focus of the treatment.

In conclusion, assay standardization and better understanding of the DBG polymorphism are crucial before this information can be assessed in a hospital and used clinically at the patient's bedside in an acute COVID-19 setup.