Key Feature: Experimental studies have shown that vitamin D exerts several biological activities that are thought to be protective against COVID-19
Reference to Original paper: Charoenngam, N., Shirvani, A., & Holick, M. F. (2021). Vitamin D and Its Potential Benefit for the COVID-19 Pandemic. Endocrine Practice, 27(5), 484–493. https://doi.org/10.1016/j.eprac.2021.03.006
CONCEPTIVE FARMACIA’S REVIEW RESEARCH ABSTRACT:
Vitamin D is known not only for its importance for bone health but also for its biologic activities on many other organ systems. This is due to the presence of the vitamin D receptor in various types of cells and tissues, including the skin, skeletal muscle, adipose tissue, endocrine pancreas, immune cells, and blood vessels. Experimental studies have shown that vitamin D exerts several actions that are thought to be protective against coronavirus disease (COVID-19) infectivity and severity. These include the immunomodulatory effects on the innate and adaptive immune systems, the regulatory effects on the reninangiotensin-aldosterone-system in the kidneys and the lungs, and the protective effects against endothelial dysfunction and thrombosis. Prior to the COVID-19 pandemic, studies have shown that vitamin D supplementation is beneficial in protecting against risk of acquiring acute respiratory viral infection and may improve outcomes in sepsis and critically ill patients. There are a growing number of data connecting COVID-19 infectivity and severity with vitamin D status, suggesting a potential benefit of vitamin D supplementation for primary prevention or as an adjunctive treatment of COVID-19. Although the results from most ongoing randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are still pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at a level of least 30 ng/mL (75 nmol/L) and preferably 40 to 60 ng/mL (100-150 nmol/L) to minimize the risk of COVID-19 infection and its severity.
CONCEPTIVE FARMACIA’S REVIEW RESEARCH HIGHLIGHTS:
· Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the new strain of coronavirus that causes coronavirus disease 2019 (COVID-19).[1,2] Due to the high infectivity and transmissibility of this novel virus, COVID-19 quickly became a global pandemic that has already affected at least 219 countries since its emergence from Wuhan, China in December 2019.2,3 The most common clinical manifestations of COVID-19 include fever, fatigue, anorexia, myalgia, cough, sputum production, and dyspnea.[4,5] the Abbreviations: ACE2, angiotensin converting enzyme 2; ARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease; IL, interleukin; IU, international units; OR, odds ratio; peripheral blood mononuclear cells (PBMCs), peripheral blood mononuclear cell; RAAS, reninangiotensin-aldosterone; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TH1, T helper 1; TH17, T helper 17; VDR, vitamin D receptor. majority of patients with COVID-19 are either asymptomatic or develop only mild respiratory symptoms, a significant number of patients develop severe complications that result in morbidity and mortality, including acute respiratory distress syndrome (ARDS), arterial and venous thrombosis, multi-organ failure, and septic shock, among others.[4,5] Factors known to be associated with increased susceptibility to severe outcomes are advanced age, cancer, immunocompromised state, chronic kidney disease, chronic respiratory disease, cardio-metabolic disorders and smoking.[6]
· Majority of patients with COVID-19 are either asymptomatic or develop only mild respiratory symptoms, a significant number of patients develop severe complications that result in morbidity and mortality, including acute respiratory distress syndrome (ARDS), arterial and venous thrombosis, multi-organ failure, and septic shock, among others.[4,5]
· Experimental studies have shown that vitamin D exerts several biological activities that are thought to be protective against COVID-19
· Prior to the COVID-era, it was reported that vitamin D supplementation is beneficial in protecting against risk of respiratory viral infection and may improve outcomes in sepsis and critically ill patients
· In a pilot study in 31 vitamin D-deficient patients who were on mechanical ventilation, administration of a single dose of enteral 500 000 or 250 000 IUs of vitamin D3 was found to decrease hospital length of stay compared with placebo.[81]. In another randomized controlled trial that gave enteral 540 000 IUs of vitamin D3 followed by monthly maintenance doses of 90 000 IU for 5 months or placebo to 475 vitamin D-deficient critically ill patients, a significant decrease in-hospital mortality was observed in the subgroup of 200 patients with serum 25(OH)D <12 ng/mL or 30 nmol/L.[82]
· The results from randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25(OH)D at a level of at least 30 ng/mL (75 nmol/ L) and preferably at 40 to 60 ng/mL (100-150 nmol/L)[12] to achieve optimal health benefits of vitamin D and minimize the risk of COVID-19 infection and its severity
CONCEPTIVE FARMACIA’S REVIEW RESEARCH SUMMARY:
· Introduction:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the new strain of coronavirus that causes coronavirus disease 2019 (COVID-19).[1,2] Due to the high infectivity and transmissibility of this novel virus, COVID-19 quickly became a global pandemic that has already affected at least 219 countries since its emergence from Wuhan, China in December 2019.2,3 The most common clinical manifestations of COVID-19 include fever, fatigue, anorexia, myalgia, cough, sputum production, and dyspnea.[4,5] the majority of patients with COVID-19 are either asymptomatic or develop only mild respiratory symptoms, a significant number of patients develop severe complications that result in morbidity and mortality, including acute respiratory distress syndrome (ARDS), arterial and venous thrombosis, multi-organ failure, and septic shock, among others.[4,5] Factors known to be associated with increased susceptibility to severe outcomes are advanced age, cancer, immunocompromised state, chronic kidney disease, chronic respiratory disease, cardio-metabolic disorders and smoking.[6].
· Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the new strain of coronavirus that causes coronavirus disease 2019 (COVID-19).[1,2] Due to the high infectivity and transmissibility of this novel virus, COVID-19 quickly became a global pandemic that has already affected at least 219 countries since its emergence from Wuhan, China in December 2019.2,3 The most common clinical manifestations of COVID-19 include fever, fatigue, anorexia, myalgia, cough, sputum production, and dyspnea.[4,5] the.
· These populations are known as being at high risk for vitamin D deficiency.9e12 vitamin D deficiency could potentially contribute to higher COVID-19 positivity, morbidity, and mortality rates appreciated in these populations
· Objectives:
The aim of this review is to discuss potential biological mechanisms by which vitamin D could be protective against COVID-19 and to summarize evidence from observational studies and clinical trials that have demonstrated the direct and indirect links between vitamin D and COVID-19.
· Results:
A cohort study in healthy adults demonstrated approximately 50% reduction in the risk of incident acute respiratory tract infection in those with serum 25(OH)D concentrations of 38 ng/mL (95 nmol/L).[72].
· A more recent meta-analysis of 25 randomized controlled trials showed that supplementation of vitamin D2 or D3 can protect against the development of acute respiratory tract infection compared with placebo.[75].
· The observed relationship was found to persist across latitudes, races, ethnicities, both sexes, and age ranges (Fig. 4).[86]
· This result is in line with that of a retrospective cohort study showing that deficient vitamin D status was associated with an increased risk of positive test for COVID-19 with likely sufficient vitamin D status after adjusting for potential confounders.[87].
· A pilot randomized clinical trial gave oral 25(OH) D3 or placebo to 76 patients with COVID-19 and showed that the treatment group had a markedly reduced rate of intensive care unit admission (2% vs 50%, P < .001).[108]
· Conclusion:
Vitamin D is known for its importance for calcium and phosphate metabolism and for its biologic actions on immune modulation.
· Experimental studies have shown that vitamin D exerts several biological activities that are thought to be protective against COVID-19.
· These include the immunomodulatory effects on the innate and adaptive immune systems, the regulatory effects on the RAAS in the kidneys and the lungs, and the protective effects against endothelial dysfunction and thrombosis.
· The results from randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25(OH)D at a level of at least 30 ng/mL (75 nmol/ L) and preferably at 40 to 60 ng/mL (100-150 nmol/L)[12] to achieve optimal health benefits of vitamin D and minimize the risk of COVID-19 infection and its severity.
CONCEPTIVE FARMACIA’S REVIEW RESEARCH FIGURES:
Figure 1: Schematic representation of paracrine and intracrine function of vitamin D and its metabolites and actions of 1,25-dihydroxyvitamin D on the innate and adaptive immune systems. 1,25(OH)2D 1⁄4 1,25-dihydroxyvitamin D; 25(OH)D 1⁄4 25-hydroxyvitamin D; IFN-Ƴ 1⁄4 interferon-Ƴ; IL 1⁄4 interleukin; MHC 1⁄4 membrane histocompatibility complex; TH1 1⁄4 T helper 1; TH2 1⁄4 T helper 2; TH17 1⁄4 T helper 17; Treg 1⁄4 regulatory T cell; TLR2 1⁄4 toll-like receptor 2; TLR4 1⁄4 toll-like receptor 4; TNF-a 1⁄4 tumor necrosis factor- a. Reproduced with permission from Holick, 2020
Figure 2: Heatmaps of vitamin D responsive genes whose expression response variation in 6 vitamin D-deficient subjects taking 10 000 international units per day of vitamin D3 for 6 months showed that 3 subjects had a robust response in gene expression compared to the other 3 subjects, who had minimum-to-modest responses even though these subjects raised their blood levels of 25(OH)D in the same range of ~60 to 90 ng/mL. 0m 1⁄4 0 month; 6m 1⁄4 6 months; 25(OH)D 1⁄4 25-hydroxyvitamin D; PTH 1⁄4 parathyroid hormone. Reproduced with permission from Holick, 2019
Figure 3. Schematic representation of the effects of 1,25(OH)2D on the renin-angiotensin-aldosterone system. SARS-CoV-2 uses the ACE2 as the main receptor entry site and downregulates ACE2 in the lungs. This causes the accumulation of angiotensin II, which causes inflammation and apoptosis in the lungs and systemic vasoconstriction by interacting with the AT1 receptor, leading to COVID-related complications including ARDS, myocarditis, and cardiac injury. 1,25(OH)2D inhibits renin and ACE and induces the expression of ACE2 in the lungs, thereby reducing the accumulation of angiotensin II. Inhibition of renin expression may also result in decreased flux of angiotensin I to angiotensin-(1-9), thereby mitigating bradykinin storm. Additionally, 1,25(OH)2D may inhibit ACE2 expression in the renal tubular cells, which is thought to be protective against COVID-associated kidney injury by reducing the viral direct cytopathic effects on the cell. 1,25(OH)2D = 1,25-dihydroxyvitamin D; ACE = angiotensin converting enzyme; ACE2 = angiotensin converting enzyme 2; ARDS = acute respiratory distress syndrome; AT1 receptor = angiotensin II type 1 receptor; COVID-19 = coronavirus disease 2019; SARS-CoV-2 = severe acute respiratory distress syndrome coronavirus 2 (Copyright Holick, 2021).
Figure 4. SARS-CoV-2 nucleic acid amplification test positivity rates and circulating 25(OH)D levels in all subjects (A) and stratified by latitude region (B), predominately Black non-Hispanic, Hispanic and White non-Hospanic zip codes (C), age group (D), and sex (E). Smooth lines represent the weighted second order polynomial regression fit to the data associating circulating 25(OH)D levels (x-axis) and SARS-CoV-2 positivity rates (y-axis). 25(OH)D = 25-hydroxyvitamin D; SARS-CoV-2 = severe acute respiratory distress syndrome coronavirus 2. (Copyright Kaufman, 202086 with permission.)