Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol.

The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin-angiotensin-bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.

The relationship between 25(OH) vitamin D levels and COVID-19 onset and disease course in Spanish patients.

OBJECTIVE: Currently, there are no definitive data on the relationship between low levels of vitamin D in the blood and a more severe disease course, in terms of the need for hospital admission, intensive care unit (ICU) stay, and mortality, in patients with coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study the association between levels of circulating 25-hydroxyvitamin D (25(OH)D) and adverse clinical outcomes linked to SARS-CoV-2 infection. We further aimed to observe the incidence of low, below-average, and normal levels of 25(OH)D in patients hospitalized for COVID-19 between March 12, 2020, and May 20, 2020, and assess whether these values differed between these patients and a normal population. Finally, we determined whether the need for transfer to the intensive care unit (ICU) and the mortality rate were related to low levels of 25(OH)D. STUDY DESIGN: Retrospective observational study. SETTING: Quironsalud Hospitals in Madrid, Spain. PARTICIPANTS: We analyzed 1549 patients (mean age, 70 years; range, 21-104 years); 835 were male (53.9 %; mean age, 73.02 years), and 714 were female (46.1 %; mean age, 68.05 years). Subsequently, infected patients admitted to the ICU (n = 112) and those with a fatal outcome (n = 324) were analyzed. PROCEDURES: Serum concentrations of 25(OH)D were measured by electrochemiluminescence. RESULTS: More hospitalized patients (66 %, n = 1017) had low baseline levels of 25(OH)D (<20 ng/mL) than normal individuals (45 %) (p < 0.001). An analysis by age group revealed that COVID-19 patients between the ages of 20 and 80 years old had significantly lower vitamin D levels than those of the normal population (p < 0.001). Patients admitted to the ICU tended to have lower levels of 25(OH)D than other inpatients (p < 0.001); if we stratified patients by 25(OH)D levels, we observed that the rate of ICU admission was higher among patients with vitamin D deficiency (p < 0.001), indicating that higher vitamin D levels are associated with a lower risk of ICU admission due to COVID-19. ICU admission was related to sex (higher rates in men, p < 0.001) and age (p < 0.001). When using a logistic regression model, we found that vitamin D levels continued to show a statistically significant relationship with ICU admission rates, even when adjusting for sex and age. Therefore, the relationship found between vitamin D levels and the risk of ICU admission was independent of patient age and sex in both groups. Deceased patients (n = 324 tended to have lower levels of 25 (OH)D that normal population of the same age (p < 0.001). CONCLUSION: Vitamin D deficiency in patients with COVID-19 is correlated with an increased risk of hospital admission and the need for critical care. We found no clear relationship between vitamin D levels and mortality.

Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COVID-19 infection. / El suplemento con altas dosis de vitaminaD podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19.

Although we lack enough evidence to justify supplementing with vitaminD in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitaminD reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INF-γ). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitaminD at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitaminD levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensinII available to cause damage. VitaminD inhibits mediators of RAAS - present in all cells of the body - and by inhibiting ACE activity and increasing ACE2, it lowers angiotensinII levels. We present studies with proposals for recommended doses of vitaminD, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitaminD for the benefit of public health and especially in times of crisis for COVID-19.