Journal Article

Evidences for a protective role of vitamin D in COVID-19

Smith, Vanessa, Cutolo, Maurizio, Paolino, Sabrina

2020

Overview

Correspondence to Professor Maurizio Cutolo; [e-mail] Introduction Vitamin D and COVID-19 A growing number of concordant reports support a protective role for vitamin D in reducing at least the risk/severity of respiratory tract infections (RTIs), especially in the influenza and COVID-19 context.1–5 Major clinical reports show that vitamin D deficiency contribute to acute respiratory distress syndrome (ARDS) SARS-CoV-2 and that case-fatality rates increase with age and the highest SARS-CoV-2 serum concentrations.6 7 In addition, the outbreak of COVID-19 seems to occur mainly in the cold winter time, when serum 25-hydroxyvitamin D (25(OH)D—calcidiol or calcifediol) concentrations are the lowest, as well as the ultraviolet B (UVB) doses, whereas the number of cases in the Southern Hemisphere near the end of summer are lower.8- Targeted 25(OH)D serum concentration measurements and vitamin D supplementation is strongly suggested have important patient and public health benefits.9 The positive role of vitamin D replacement therapy (vDRT) in reducing risk and severity in COVID-19 patients is supported by several clinical evidences and RCTs are undergoing, however, previous experiences of RCT related to vDRT are available from other lung viral infection studies and even in mechanically ventilated adult intensive care unit (ICU) patients.10–14 These important observations are corroborated by several biological/molecular mechanisms through vitamin D can generally reduce risk of infections and downregulate the immune/inflammatory reaction. The discovered presence of the VDR in activated T cells and monocytes, first suggested in 1983 that vitamin D may have a role in the function of the immune system.19 As matter of fact, vitamin D has received increased worldwide attention for its involvement in reducing risk for several chronic diseases, besides infectious diseases, including type 1 diabetes and notably autoimmune rheumatic diseases for the reason that may interfere with the immune system.20 The biological/molecular evidence for the interactions of vitamin D with the immune response is that its final active metabolite, namely calcitriol (1,25(OH)2D3), due to its structural origin from cholesterol, is molecularly considered a steroid hormone (D-hormone) like others (ie, sex hormones, cortisol) and analogously to glucocorticoids (and sex hormones) can exerts immunomodulatory/antinflammatory activities through functional cell steroid receptors21–23 (figure 1). Furthermore, the intensity and quality of the host immune/inflammatory response seems to influence the clinical severity and mortality risk associated with viral diseases (such as influenza and COVID-19) rather than the viral pathogen itself.24 25 Consequently, it is biologically plausible that 1,25(OH)2D3 may exert immunomodulatory effects also in COVID-19 patients, playing a role in the regulation of both innate and adaptive immunity.26 The intracellular conversion of 25(OH)D (calcidiol or calcifediol) into the active metabolite 1,25(OH)2D3, (calcitriol), through the intracrine actions of the enzyme 1-alpha-hydroxylase (CYP27B1), is distinct from the 1,25(OH)2D3 produced in kidneys and released into the systemic circulation; however, both have autocrine and paracrine functions that enhance host immunity, for example, by upregulating the antimicrobial peptides cathelicidin and alpha-defensin26 (figure 1). Conclusion, vitamin D deficiency seems a prevalent and further risk factor for severe COVID-19 male patients.39 Vitamin D and RTIs: lesson from the recent experience The seasonality of viral RTIs such as those caused by influenza virus and rhinovirus has been recognised from long time and is even considered to be one of the major contributor to seasonal variations in human mortality.40 As matter of fact, a recent large study found that sunlight UV radiation dose is negatively correlated with the percent positive patients for SARS-CoV-2 and for four other common human coronaviruses in the USA, and this association is season-related with lowest vitamin D serum concentrations.41 In a large population survey (6789 participants), the prevalence of RTIs and altered lung function showed a strong seasonal pattern and linear association in the opposite direction to the vitamin D serum concentrations.42 A more detailed study evaluating the link between vitamin D concentrations and ARDS, patients with 25(OH)D3 <20 ng/mL showed a significantly higher odds of ARDS compared with patients with 25(OH)D >20 ng/mL after adjustment for age, gender, diagnostic category, staging and degree of cigarette consumption, (p=0.032).7 Interestingly, when 25(OH)D concentrations were analysed with logistic regression as a continuous exposure in 0.4 ng/mL increments, the odds of ARDS decreased by 17% for every 0.4 ng/mL increase in 25(OH)D (OR 0.83 (95% CI 0.69 to 0.98; p=0.033).7 In another study, it was found that each 4 ng/mL increase in 25(OH)D was associated with a 7% lower risk of lung infection (95 % CI 3% to 11 %) after adjustment for lifestyle, socioeconomic factors and adiposity.42 Therefore, it has been argued that vitamin D status should be taken into account as an important contributor in determining the population susceptibility to seasonal epidemic outbreaks, together with the effects of augmented indoor confinement in wintertime (ie, school) and increased circulating reservoirs of respiratory viruses.43 Furthermore, another large observational study evaluating healthy adults during the fall and winter of 2009–2010, investigated the relationship between serum 25(OH)D concentrations and incidence of acute RTIs (ARTIs).44 The result was that only 17% of patients showing serum 25(OH)D concentrations over 38

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adaptive immunity / Antibodies / Coronaviruses / COVID-19 / COVID-19 - blood / COVID-19 - immunology / COVID-19 - prevention & control / Cytokine storm / Dietary Supplements / Epidemics / Health care / Hormones / Humans / Immune system / Immunomodulators / Infections / Influenza / Lymphocytes / Miscellaneous / Mortality / Pathogens / Pulmonary fibrosis / Severe acute respiratory syndrome coronavirus 2 / Tumor necrosis factor-TNF / Viral infections / Vitamin D / Vitamin D - blood / Vitamin D - therapeutic use / Vitamin D Deficiency - complications / Vitamin deficiency