Calcemia and phosphoremia

Calcemia and phosphoremia were measured in all participants. They all had normal values, except one person who was hypercalcemic.

SARS-CoV-2 infection

From September 1st, 2020 to January 31st, 2021, thirteen participants (20%) were infected with SARS-CoV-2. Although, no cases required hospitalization or respiratory support. The outcome of all cases was favorable. The finding showed that clinical symptoms were mild without pneumonia manifestation. Headache, fatigue, loss of smell and/or taste and myalgia were the most common symptoms (Figure 1 and Table 4).

Discussion

The high prevalence of hypo-vitaminosis D was reported in several studies [8,16]. This vitamin deficiency affects all age groups and it is therefore a public health problem [17].

There is no consensus on what VITD insufficiency and deficiency are; neither there are available determined references values, which have given rise to many discussions in recent years. Unlike most biological parameters, reference values for VITD are not established by taking the extreme values of a reference population including apparently healthy individuals. Indeed, depending on the factors influencing VITD synthesis, the concentrations of 25 (OH) D can change greatly. It is therefore recommended to determine 25 (OH) D concentrations below of which, bones health is affected (which is related with Para Thyroid Hormone (PTH) elevation), as well as the concentrations for which beneficial effects have been demonstrated in intervention studies. This method, "health-based reference values", is based on an analysis of data from the literature. Organizations such as the IOF (International Osteoporosis Foundation), the GRIO (Osteoporosis Research and Information Group) and the US Endocine Society distinguish three levels of VITD measurement: deficiency, insufficiency and optimal level [18- 21]. These organizations agree on a minimum recommended concentration of 30 ng/ml. Regarding the deficiency, the US endocrine society considers the threshold to be 20 ng/ml, unlike the others for whom the deficiency threshold is 10 ng/ml. The insufficiency/deficiency barrier is set at 10 ng/ ml mainly based on the Para Thyroid Hormone (PTH) measurement [21, 22]. Indeed, above 10 ng/ml, Chapuy et al. have demonstrated that PTH remains at a stable level, (approximately 36 pg/ml) [23]. However, below 10 ng/ml, PTH concentrations increase, with a risk of bone mineralization [24].

In our study, despite sun exposure and consumption of vitamin D-rich foods, hypovitaminosis D was still too high among the participants. In fact, only 8% of them had optimal VITD levels. These results are consistent with the study conducted by Allali et al. in Rabat city in a group of women in whom hypovitaminosis D was 91% and the mean value of 25 (OH) D was 18.1 ± 7.9 ng/ml [25]. Comparing to our study, this value was 16.2 ± 6.7 ng/ml in the group of women. According to a Tunisian study conducted in 2016 and 2017, the average VITD level in healthy women was 7.88 ± 6.08 ng/ml [26].

In France, Deplanque et al. revealed that 92.3% of healthy subjects present a VITD level strictly below 30 ng/ml [27]. The systematic review, published by Hilger et al. in 2014, reported a large variability in the mean and median value of 25(OH) D worldwide, even between different studies within the same country or regions [16].

The main active form of VITD is calcitriol (1.25 (OH) 2D3), the last metabolite whose synthesis begins at the cutaneous level under the effect of UVB, then hydroxylated in the liver and finally dihydroxylated in the kidneys [28]. VITD is stored in the human body in the form of 25 (OH) D, which is also the circulating form that enables the assessment of vitamin status and which will be transported to the various tissues in need via the blood [3,29].

Since VITD is known for its multiple health benefits, its deficiency can lead to serious health problems affecting many tissues and organs [17,30]; including the accumulation of osteoid, which results in rickets in children and bone fissures caused by osteomalacia in adults. It also has pleiotropic effects on muscles and immune system [31,32]. In addition, VITD has many protective roles against various conditions. However, the extra-bone effects of VITD are explained by the presence of vitamin D-specific receptors in most human tissues [17].

The broad and complex role of VITD in the regulation of the immune system has been supported by several studies; it appears that it modulates innate and adaptive immunity; the VDR (VITD receptor) and 1 α-hydroxylase are expressed on lymphocytes (T and B), on macrophages and on antigen presenting cells, after fixation of 25 (OH) D, these cells will convert it into its active metabolite which will act on the surrounding immune system [33-35].

Mounting evidence indicates that VITD is strongly linked to pathogens elimination. In fact, the toll-like receptor 2/1 and 25OHD3 combination stimulate cathelicidin expression; an antimicrobial protein implicated in cytokine recruitment and macrophage differentiation [36].

Moreover, VITD can increase the production of regulatory T cells through the adaptive immune response. Randomized controlled trials in healthy adults have consistently shown that a significant reduction in respiratory tract infections has been confirmed in people taking daily VITD supplementation compared with controls [37]. A meta-analysis of nine studies by Laplana et al. settled that VITD can inhibit enveloped viruses [38]. Furthermore, inadequate VITD levels in the elderly are associated with weakened innate immune activity [39]. A recent study conducted by Wei et al. found that 70.3% of elderly people in China have been defined as VITD deficient [40].

In response to the global outbreak of COVID-19 pandemic, several studies were conducted to reveal approaches that can reduce the severity of respiratory symptoms while waiting for the vaccine to become widely available. According to Ilie et al. it was demonstrated that the highest rates of infection and mortality from COVID-19 were found in populations with low VITD levels [41]. Despite the increased exposure to sunlight of some countries, such as Spain and Italy, VITD deficiency is still observed. Consequently, mortality due to COVID-19 was very pronounced. Whereas in Norway and Sweden, where VITD supplementation and food fortification are more common, mortality and infection rates were lower [41,42]. Hence, several studies as the previous have been supporting the protective role of VITD against COVID-19 [12,43-45].

In the current study, after VITD supplementation, we monitored all participants to determine who would contract COVID-19. Among the thirteen (20%) COVID-19 positive cases, 11 (85%) were females, of whom 3 cases had VITD deficiency and 8 had VITD insufficiency. The other two infected males were insufficient for VITD. None of them had developed acute complications, neither had needed hospitalization. This might be explained by the protective role of VITD against COVID-19 that has been reported by several worldwide studies.

Knowing that hypo-vitaminosis D increases the risk of contracting COVID-19 to 54%, Kaufman et al. reported the important impact of VITD on reducing the possibility of contracting SARS-CoV-2 infection as well as its severe respiratory symptoms [46]. A similar finding was reported in several studies regarding the protective role of VITD against SARS-CoV-2 infection. Castillo et al. reported that calcifediol can significantly reduce the admission of COVID-19 patients to Intensive Care Units (ICU) [47]. In the same sense Vassiliou et al. showed that COVID-19 non-survivor’s cases had lower 25 (OH) D levels at ICU admission comparing to survivors. This finding shows that there is a potential link of low levels of 25 (OH) D with poor prognosis among patients with COVID-19 pneumonia [48]. In the Indian population, two studies were realized in order to analyze the impact of VITD level on COVID-19 severity. They revealed a significant association of the lower levels of 25 (OH) D with SARS-CoV-2 related deaths and the susceptibility to infection [49,50]. In a further turkish study, Karahan and Katkat, concluded that the mean serum 25 (OH)D level was significantly lower in patients with severe-critical COVID-19 comparing to moderate COVID-19 (10.1 ± 6.2 vs. 26.3 ± 8.4 ng/mL, p<0.001) [51]. Whereas, according to Ling et al., highdose of cholecalciferol supplementation, apart from baseline serum 25 (OH) D levels, appears to be associated with a reduced risk of mortality due to COVID-19. The study also suggests that serum 25 (OH) D levels were not associated with COVID-19 mortality [52].

Conclusion

Hypo-vitaminosis D remains one of the most prevalent public health concerns worldwide. Based on the results obtained in the current study and given the protective role of VITD against COVID-19, the high prevalence of hypo-vitaminosis D should be managed in order to improve public health status and consequently decrease the mortality rate. Thus, it is essential to support the immune system of people at risk, especially COVID-19 front line health workers, by prescribing VITD supplementation. It is as important to develop a public health policy to reduce the hypo-vitaminosis D consequences in the Moroccan population.

Conflict of Interest

The author has no conflict of interest to declare.

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