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      SARS‐CoV‐2 pandemic and Vitamin D deficiency—A double trouble

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          Abstract

          Dear Editor, The current SARS‐CoV‐2 pandemic has mandated significant isolation measures. Streets in affected countries are mostly empty, and many individuals spend several consecutive days at home to reduce the risk of infection. While determinant for pandemic control, home reclusion may have a significant toll on the health of individuals. One relevant area where we are yet to see proper discussion and strategies pertains to vitamin D deficiency. Vitamin D is a fat‐soluble hormone that plays a significant role in calcium‐phosphate metabolism, in addition to intervening in cell metabolic activity, immune regulation, among other functions. Vitamin D is synthesized in skin epithelium under ultraviolet B (UVB) radiation. It then undergoes two successive hydroxylations in the 25‐ and 1‐ carbons, in the liver and in the kidney, respectively, to yield the active form, calcitriol. A minor portion of vitamin D is obtained from alimentary sources. The time of exposure to solar radiation sufficient to produce the necessary daily amounts of vitamin D is yet matter of discussion, as it depends heavily on the incident radiation (thus varying according to season, latitude and hour of the day), as well as on individual characteristics such as age, clothing, sunscreen use or skin phototype. Modern life has significantly reduced daily exposure to solar radiation, as most activities are carried indoors. It comes as no surprise that vitamin D deficiency is common in Western countries. Nationwide data from the United States of America suggests 40% of adults may have vitamin D deficiency. 1 While this prevalence may be higher at nursing homes, 2 prevalence of about 10% and 60% has been found in paediatric age 3 and free‐living healthy young adults, 4 respectively. Home reclusion in the context of social isolation measures to fight SARS‐CoV‐2 pandemic may lead to a surge in vitamin D across the world, causing significant harms. The consequences of vitamin D deficiency have been extensively reviewed, 5 , 6 , 7 but are important to be highlighted in the current context. Vitamin D deficiency has been associated with developing both type 1 and type 2 diabetes, cognitive decline, malignant neoplasms, autoimmune diseases, cardiovascular diseases, osteoporosis, risk of fall in the elderly and overall mortality. The risk of fracture may further be heightened in elderly patients as daily physical activity may be diminished during lockdown, as may physical therapy and rehabilitation treatments. This leads to reduction the beneficial mechanical stimulus that promotes bone mineralization, as well as loss of physical strength, coordination and balance that may predispose to falling and bone fractures. Furthermore, it may be an independent risk factor for infection, severe sepsis and mortality in critically ill patients, 8 thus raising the possibility of contributing towards worse outcomes in the event of COVID‐19 infection. The fight against SARS‐CoV‐2 is far from over and will significantly impact society over the coming months. As such, it is paramount that we identify rising problems and address them as soon as possible to prevent dire complications. Regarding vitamin D deficiency, simple measures can be adopted to prevent, identify and treat this condition. Solar exposure could be recommended as a general advice for the entire population. While individuals should avoid breaking confinement, solar exposure of the face and bare upper limbs over a window or on a balcony may suffice to produce the necessary amounts of vitamin D. Patients should be informed that glass blocks UVB transmission and as such direct solar exposure is necessary. Caution should also be heeded to avoid excessive solar exposure as this may carry unwanted harms. While precise recommendations on ideal time of exposure cannot be offered due to the abovementioned variability, a sensible total exposure of 20‐40 minutes, divided in two periods across the day may be adequate to prevent significant vitamin D deficiency. Increased intake of vitamin D through diet could also be recommended. Egg yolks, oily fish, dairy products and mushrooms are generally good sources for vitamin D, and their intake may be preferred over other low‐vitamin D food. However, increasing natural intake of vitamin D may not be easy during isolation, as commerce is running slowly and people avoid frequent shopping, thus preferring long shelf‐life foods over fresh produce. Global supplementation has not been advocated under normal circumstances. However, under the current pandemic, further thought should be given to this matter, particularly if home confinement is prolonged over the coming months, considering the low toxicity of these supplements when administered at standard dosage. Evidence shows vitamin D supplementation significantly reduces the risk for respiratory infections, particularly in those with deficiency 9 and has been advocated for COVID‐19. 10 Additional consideration should be given to the elderly, as the risks for bone mass imbalance is higher in this age group. The daily requirements for vitamin D vary according to age and preexisting conditions, but intake up to 4000 UI/day in adults and elderly seems to be safe, posing no risk of adverse effects. 11 Thus, 400‐2000 UI of vitamin D3 supplementation could assist in preventing vitamin D deficiency during lockdown, without significant risk for harms. Serum vitamin D dosing should be offered to all individual at high risk for vitamin D deficiency during or immediately after this crisis, to identify those at need for treatment. If vitamin D deficiency is diagnosed, treatment should be conducted according to international guidelines, based on age and comorbid conditions. Vitamin D deficiency may become a significant public health issue as consequence of lockdown measures implemented to fight SARS‐CoV‐2. Sensible solar exposition over open windows or on balconies may suffice to prevent over vitamin D deficiency. As food availability is also limited during this crisis, supplementation should be administered particularly to those at highest risk for complications. Global supplementation should be considered as a public health policy, as the risks of such an intervention are minimal. Testing may be advised in high‐risk individuals, where prophylactic supplementation may not be sufficient to solve previously established deficiencies. Yours sincerely CONFLICT OF INTEREST None declared.

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          Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

          The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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            Vitamin D: an evidence-based review.

            Vitamin D is a fat-soluble vitamin that plays an important role in bone metabolism and seems to have some anti-inflammatory and immune-modulating properties. In addition, recent epidemiologic studies have observed relationships between low vitamin D levels and multiple disease states. Low vitamin D levels are associated with increased overall and cardiovascular mortality, cancer incidence and mortality, and autoimmune diseases such as multiple sclerosis. Although it is well known that the combination of vitamin D and calcium is necessary to maintain bone density as people age, vitamin D may also be an independent risk factor for falls among the elderly. New recommendations from the American Academy of Pediatrics [corrected] address the need for supplementation in breastfed newborns and many questions are raised regarding the role of maternal supplementation during lactation. Unfortunately, little evidence guides clinicians on when to screen for vitamin D deficiency or effective treatment options.
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              Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012)

              Introduction 1,25-dihydroxyvitamin D3 (cholecalciferol), the hormonally active form of vitamin D3, is a lipid-soluble compound that plays a significant role in clinical medicine due to its potent effects on calcium homeostasis and bone metabolism. Since foods containing natural vitamin D are rare, the primary source of the compound remains its nonenzymatic dermal synthesis through exposure to ultraviolet rays in sunlight. Although uncommon in most developed countries, recent literature has demonstrated that subclinical vitamin D deficiency can exist in certain populations and plays a role in downstream clinical consequences, including cardiovascular disease, cancer, diabetes, osteoporosis, and fractures. This study aims to identify the prevalence and change in the pattern of vitamin D deficiency in subpopulations throughout the United States to provide a foundation for further clinical studies correlating the clinical outcomes to vitamin deficiency. Methods Data analyzed in this study were collected through National Health and Nutrition Examination Survey (NHANES), specifically from a population of 4962 participants, age ≥20 years, who were hospitalized between 2011 and 2012. This cohort was stratified to divide the population into patients that were vitamin D sufficient (>50 nmol/L) versus patients who were vitamin D deficient (50 nmol/L). The risk factors were compared between the subpopulations in 2005-2006 and 2011-2012. Conclusions The prevalence of vitamin D deficiency is greater in certain clinical subpopulations, and the presence of associated characteristics should raise the index of suspicion for the practicing clinician with regard to conditions associated with vitamin D deficiency, such as osteoporosis and osteomalacia. Further research investigating the pathophysiology of hypovitaminosis D and its clinical consequences can help better understand and prevent the development of associated comorbidities.
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                Author and article information

                Contributors
                migueldbalpalhao@campus.ul.pt
                Journal
                Photodermatol Photoimmunol Photomed
                Photodermatol Photoimmunol Photomed
                10.1111/(ISSN)1600-0781
                PHPP
                Photodermatology, Photoimmunology & Photomedicine
                John Wiley and Sons Inc. (Hoboken )
                0905-4383
                1600-0781
                11 June 2020
                : 10.1111/phpp.12579
                Affiliations
                [ 1 ] Dermatology Department Hospital de Santa Maria Centro Hospitalar Universitário Lisboa Norte EPE Lisbon Portugal
                [ 2 ] Dermatology Universitary Clinic, Faculty of Medicine University of Lisbon Lisbon Portugal
                [ 3 ] Dermatology Research Unit, iMM João Lobo Antunes University of Lisbon Lisbon Portugal
                Author notes
                [*] [* ] Correspondence

                Miguel Alpalhão, Dermatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte EPE, Av. Prof. Egas Moniz, 1649‐035 Lisbon, Portugal.

                Email: migueldbalpalhao@ 123456campus.ul.pt

                Author information
                https://orcid.org/0000-0001-7672-0395
                Article
                PHPP12579
                10.1111/phpp.12579
                7301043
                32476189
                03ae325c-b026-4a60-ab78-82a35973e276
                © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 03 May 2020
                : 12 May 2020
                : 23 May 2020
                Page count
                Figures: 0, Tables: 0, Pages: 2, Words: 3283
                Categories
                Letter to the Editor
                Letters to the Editor
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:18.06.2020

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