{"id":85288,"date":"2021-09-21T10:33:22","date_gmt":"2021-09-21T14:33:22","guid":{"rendered":"http:\/\/stateofthenation.co\/?p=85288"},"modified":"2021-09-21T10:46:09","modified_gmt":"2021-09-21T14:46:09","slug":"science-paper-link-between-vitamin-d-deficiency-and-covid-19-incidence","status":"publish","type":"post","link":"http:\/\/stateofthenation.co\/?p=85288","title":{"rendered":"SCIENCE PAPER: Link between Vitamin D Deficiency and COVID-19 Incidence"},"content":{"rendered":"<p><!--more--><\/p>\n<div class=\"citation\">\n<div class=\"citation__top\">\n<nav class=\"article__breadcrumbs separator\"><a class=\"article__tocHeading\" href=\"https:\/\/www.liebertpub.com\/journal\/hs\">Health Security<\/a><a class=\"article__tocHeading\" href=\"https:\/\/www.liebertpub.com\/toc\/hs\/19\/3\">Vol. 19, No. 3<\/a><\/nav>\n<p><span class=\"citation__top__item article__tocHeading\">Original Articles<\/span><span class=\"citation__top__item article__access\"><span class=\"article__access__type\" title=\"This content is available for free\"><i class=\"citation__acess__icon icon-lock_open\" aria-hidden=\"true\"><\/i><span class=\"citation__access__type\">Free Access<\/span><\/span><\/span><\/p>\n<\/div>\n<h1 class=\"citation__title\">Association Between Vitamin D Deficiency and COVID-19 Incidence, Complications, and Mortality in 46 Countries: An Ecological Study<\/h1>\n<div class=\"loa-wrapper hidden-xs\">\n<div id=\"sb-1\" class=\"accordion\">\n<div class=\"accordion-tabbed loa-accordion\">\n<div class=\"accordion-tabbed__tab-mobile accordion__closed \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Javier Mariani\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a1\" data-db-target-for=\"a1\">Javier Mariani<\/a><span class=\"author-name\">,\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Virna Margarita Mar\u00edn Gim\u00e9nez\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a2\" data-db-target-for=\"a2\">Virna Margarita Mar\u00edn Gim\u00e9nez<\/a><span class=\"author-name\">,\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Ivana Bergam\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a3\" data-db-target-for=\"a3\">Ivana Bergam<\/a><span class=\"author-name\">,\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Carlos Tajer\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a4\" data-db-target-for=\"a4\">Carlos Tajer<\/a><span class=\"author-name\">,\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Laura Antonietti\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a5\" data-db-target-for=\"a5\">Laura Antonietti<\/a><span class=\"author-name\">,\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Filipe Inserra\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a6\" data-db-target-for=\"a6\">Filipe Inserra<\/a><span class=\"author-name\">,\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Le\u00f3n Ferder\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a7\" data-db-target-for=\"a7\">Le\u00f3n Ferder<\/a><span class=\"author-name\">, and\u00a0<\/span><\/div>\n<div class=\"accordion-tabbed__tab-mobile \"><a class=\"author-name accordion-tabbed__control visible-x\" title=\"Walter Manucha\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-id=\"a8\" data-db-target-for=\"a8\">Walter Manucha<i class=\"icon-Email\" aria-hidden=\"true\"><\/i><\/a><\/div>\n<div><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"epub-section\"><span class=\"epub-section__item\"><span class=\"epub-section__state\">Published Online:<\/span><span class=\"epub-section__date\">7 Jun 2021<\/span><\/span><span class=\"epub-section__item\"><a class=\"epub-section__doi__text\" href=\"https:\/\/doi.org\/10.1089\/hs.2020.0137\">https:\/\/doi.org\/10.1089\/hs.2020.0137<\/a><\/span><\/div>\n<div class=\"scroll-to-target fixed-element\">\n<nav class=\"trans coolBar stickybar\">\n<div class=\"stickybar__wrapper coolBar__wrapper clearfix\">\n<div class=\"rlist coolBar__zone\"><\/div>\n<ul class=\"rlist coolBar__first\" data-cb-group=\"Article\" data-cb-group-icon=\"icon-toc\">\n<li class=\"coolBar__section coolBar--sections\"><a class=\"coolBar__ctrl w-slide__btn\" title=\"Sections\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#\" data-db-target-for=\"sections\" data-db-switch=\"icon-close_thin\" data-slide-target=\"#sectionMenu\"><i class=\"icon-Icon_Section-menu\" aria-hidden=\"true\"><\/i>Sections<\/a><\/li>\n<li class=\"coolBar__section coolBar--download hidden-xs hidden-sm\">\n<div class=\"w-slide--list coolBar__single cloned hidden-xs hidden-sm\"><a class=\"coolBar__ctrl\" href=\"https:\/\/www.liebertpub.com\/doi\/reader\/10.1089\/hs.2020.0137\"><i aria-hidden=\"true\"><\/i>PDF\/EPUB<\/a><\/div>\n<\/li>\n<\/ul>\n<\/div>\n<\/nav>\n<\/div>\n<div class=\"article__body \">\n<div class=\"hlFld-Abstract\">\n<h2 id=\"d1302684e1\" class=\"article-section__title section__title\">Abstract<\/h2>\n<div class=\"abstractSection abstractInFull\">\n<p>Each patient&#8217;s immune defenses play a major role in mitigating the impact (ie, morbidity and mortality) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Vitamin D is an important modulator of the immune system. Although serum 25-hydroxyvitamin D levels can be raised through diet or supplements, most vitamin D in the body is the result of dermal synthesis from ultraviolet radiation. The production of vitamin D in the skin, however, can be limited by latitude, skin-covering clothes, the use of sunblock, and skin pigmentation. Vitamin D deficiency affects a high percentage of the world population. Serum 25-hydroxyvitamin D levels are suboptimal, not only in specific risk groups but also in adults from many countries. Low vitamin D levels, therefore, represent a risk factor for several different pathologies, including SAR-CoV-2. This study used an ecological design to assess the association between vitamin D deficiency and COVID-19 incidence, complications, and mortality across 46 countries. All data were obtained from published sources. The results of the study suggest an association at the population level between the prevalence of vitamin D deficiency and the risk of being infected with COVID-19, severity of the disease, and risk of dying from it.<\/p>\n<\/div>\n<\/div>\n<div class=\"clt-dropzone\" data-pb-dropzone=\"clt-dropzone\"><\/div>\n<div class=\"hlFld-Fulltext\">\n<h2 id=\"_i1\" class=\"article-section__title section__title\">Introduction<\/h2>\n<p>Each patient&#8217;s immune defenses play a major role in mitigating the impact (ie, morbidity and mortality) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19).<sup><a id=\"B1R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B1\" data-tab=\"pane-pcw-references\">1<\/a><\/sup>\u00a0The patient&#8217;s immune-inflammatory response is notably involved in the physiopathogenesis of this viral disease, in which multiple cellular pathways and components, including vitamin D,<sup><a id=\"B2R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B2\" data-tab=\"pane-pcw-references\">2<\/a><\/sup>\u00a0are implicated. Vitamin D is an important modulator of the immune system.<sup><a id=\"B3R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B3\" data-tab=\"pane-pcw-references\">3<\/a><\/sup>\u00a0Specifically, vitamin D exerts anti-infectious and immunomodulatory action by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Vitamin D reduces the production of inflammatory cytokines, such as interleukin-2 and interferon-gamma. Furthermore, in close connection, multiple pleiotropic effects have been demonstrated on the actions of vitamin D at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections.<sup><a id=\"B4R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B4\" data-tab=\"pane-pcw-references\">4<\/a><\/sup><\/p>\n<p>Vitamin D levels, measured by serum 25-hydroxyvitamin D [25(OH)D] concentration, increase after exposure of skin to sunlight and decrease during the \u201cdark months\u201d of the year (when skin is usually covered), fluctuating from 30% to 50% in some cases.<sup><a id=\"B5 B6 B7R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B5%20B6%20B7\" data-tab=\"pane-pcw-references\">5-7<\/a><\/sup>\u00a0Although 25(OH)D levels can be raised through diet or supplements, most vitamin D in the body (between 50% and 90%) is the result of dermal synthesis from ultraviolet radiation. The production of vitamin D in the skin, however, can be limited by latitude, skin-covering clothes, the use of sunblock, and skin pigmentation.<sup><a id=\"B8R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B8\" data-tab=\"pane-pcw-references\">8<\/a><\/sup><\/p>\n<p>In addition to its nonenzymatic synthesis, vitamin D is enzymatically converted into its active form\u20141,25-dihydroxyvitamin D [1,25(OH)<sub>2<\/sub>D]\u2014in the kidneys and liver mainly, although it is also produced in other organs, tissues, and cells, such as prostate, placenta, lungs, brain, and immune cells.<sup><a id=\"B9R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B9\" data-tab=\"pane-pcw-references\">9<\/a>,<a id=\"B10R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B10\" data-tab=\"pane-pcw-references\">10<\/a><\/sup>\u00a0Vitamin D is a steroid hormone, and 1,25-(OH)<sub>2<\/sub>D is the ligand for the vitamin D receptor. Cells lacking the vitamin D receptor are the exception rather than the rule, and this widespread distribution underlies the potential myriad of physiological actions for vitamin D.<sup><a id=\"B11R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B11\" data-tab=\"pane-pcw-references\">11<\/a><\/sup><\/p>\n<p>International consensus on the definition of vitamin D deficiency is lacking; however, it is accepted that a serum 25(OH)D level of 20 nanograms per milliliter (ng\/mL)<a class=\"ref fn\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#fn1\">*<\/a>\u00a0is the threshold of sufficiency for 97.5% of the population in terms of bone health.<sup><a id=\"B5R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B5\" data-tab=\"pane-pcw-references\">5<\/a><\/sup>\u00a0Vitamin D deficiency is highly prevalent and affects a high percentage of the world population.<sup><a id=\"B12R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B12\" data-tab=\"pane-pcw-references\">12<\/a><\/sup>\u00a0Serum 25(OH)D levels are not only suboptimal in specific risk groups but also in adults from many countries\u2014especially in the Middle East and Asia, where vitamin D deficiency in adults is highly prevalent.<sup><a id=\"B13R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B13\" data-tab=\"pane-pcw-references\">13<\/a><\/sup>\u00a0The lack of sufficient levels of serum vitamin D in communities has shown greater susceptibility to a broad spectrum of diseases, in addition to the classically described bone disorders.<sup><a id=\"B14R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B14\" data-tab=\"pane-pcw-references\">14<\/a>,<a id=\"B15R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B15\" data-tab=\"pane-pcw-references\">15<\/a><\/sup>\u00a0It has been found that low vitamin D levels represent a risk factor for several different pathologies, such as autoimmune, neurodegenerative, and cardiovascular diseases, as well as diabetes, osteoporosis, cancer, and infectious diseases such as viral infections.<sup><a id=\"B12R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B12\" data-tab=\"pane-pcw-references\">12<\/a><\/sup>\u00a0Accordingly, vitamin D has been associated with the current pandemic because of its potential role in reducing the risk of SAR-CoV-2 infection.<sup><a id=\"B16R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B16\" data-tab=\"pane-pcw-references\">16<\/a>,<a id=\"B17R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B17\" data-tab=\"pane-pcw-references\">17<\/a><\/sup><\/p>\n<p>Of special interest, vitamin D has important antiviral properties, including the induction of cathelicidin and \u03b22-defensins synthesis.<sup><a id=\"B18R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B18\" data-tab=\"pane-pcw-references\">18<\/a><\/sup>\u00a0Cathelicidin and \u03b22-defensins exert significant antibiotic and antiviral effects. These pluripotent peptides have a crucial role in innate immunity, and their regulation is abnormal in hypovitaminosis D.<\/p>\n<p>This study aimed to assess the association of vitamin D deficiency on COVID-19 incidence, complications, and mortality in 46 countries.<\/p>\n<h2 id=\"_i2\" class=\"article-section__title section__title\">Methods<\/h2>\n<h3 id=\"_i3\" class=\"article-section__title\">Design<\/h3>\n<p>This study used an ecological design to correlate COVID-19 infection risk and outcome variables and vitamin D deficiency levels at the country level. All data were obtained from online published sources. Since all of the data were anonymized and publicly available, no ethical approval was sought.<\/p>\n<h3 id=\"_i4\" class=\"article-section__title\">Vitamin D Deficiency<\/h3>\n<p>Vitamin D deficiency was defined as a 25(OH)D serum level of less than 20\u2009ng\/mL.<sup><a id=\"B5R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B5\" data-tab=\"pane-pcw-references\">5<\/a>,<a id=\"B19R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B19\" data-tab=\"pane-pcw-references\">19<\/a><\/sup>\u00a0Data for national prevalence estimates of vitamin D deficiency were obtained from population studies reported elsewhere,<sup><a id=\"B5R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B5\" data-tab=\"pane-pcw-references\">5<\/a>,<a id=\"B13R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B13\" data-tab=\"pane-pcw-references\">13<\/a>,<a id=\"B20R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B20\" data-tab=\"pane-pcw-references\">20<\/a><\/sup>\u00a0and are expressed as the estimated percentage of population with vitamin D deficiency. If more than 1 estimate was found, the more conservative (ie, the lower prevalence) and those corresponding to the broadest population representation (ie, the majority of population subgroups) were used.<\/p>\n<h3 id=\"_i5\" class=\"article-section__title\">COVID-19 Cases, Tests, and Mortality<\/h3>\n<p>Data on the number of COVID-19 cases, number of tests performed, number of deaths from COVID-19, and population were obtained from Worldometer.<sup><a id=\"B21R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B21\" data-tab=\"pane-pcw-references\">21<\/a><\/sup>\u00a0This website collects and publish information from country&#8217;s official channels. We used data as published on July 4, 2020. We also obtained population data from this website to estimate the population incidence of COVID-19 infection and the population COVID-19 death rates.<\/p>\n<p>Cases are reported as the cumulative number of individuals who tested positive for COVID-19 with a confirmed laboratory result and as rates per millions of people. Tests are reported as the cumulative number of diagnostic tests performed in a given country and as the number of tests per millions of people. Mortality is reported as the cumulative number of COVID-19 deaths and the rate per millions of people. All deaths for every country are counted in the rate, from the inception of each country&#8217;s first case.<\/p>\n<h3 id=\"_i6\" class=\"article-section__title\">Gross Domestic Product<\/h3>\n<p>Data on national gross domestic product (GDP) were obtained from the World Bank&#8217;s DataBank. GDP for the year 2019 (in billions of US dollars) were used for analysis.<sup><a id=\"B22R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B22\" data-tab=\"pane-pcw-references\">22<\/a><\/sup><\/p>\n<h3 id=\"_i7\" class=\"article-section__title\">Data Extraction<\/h3>\n<p>All data were extracted by 2 researchers to a worksheet designed ad hoc. All data were extracted as published from the aforementioned sources without further modifications. All discrepancies were resolved by consensus. Only countries with available data for vitamin D status were included (data for COVID-19 indicators and GDP were available for all countries). After extraction, the case fatality ratio was computed as the cumulative number of deaths per cumulative number of cases, and the positivity ratio was computed as the cumulative number of cases per cumulative number of tests performed.<\/p>\n<h3 id=\"_i8\" class=\"article-section__title\">Statistical Analysis<\/h3>\n<p>Descriptive statistics were expressed as medians and interquartile ranges (IQR). Comparisons across vitamins D deficiency quintiles were conducted using the Kruskal-Wallis test. The correlation between COVID-19 incidence, positivity ratio, case fatality ratio, and death rate were evaluated using Spearman&#8217;s correlation coefficient. Furthermore, scatterplots with nonlinear regression lines (ie, local regression) were constructed to present correlation analysis.<\/p>\n<p>To assess the association between COVID-19 indicators and vitamin D deficiency, multivariate Poisson regression models were constructed. Quintiles of vitamin D deficiency at the population level were included as independent variables, and COVID-19 indicators as dependent variables. All models were adjusted for GDP using log transformation. Results are reported as incidence rate ratios (IRR) with their corresponding 95% confidence intervals. All tests were 2-tailed and a\u00a0<i>P<\/i>\u00a0value of less than .05 is considered statistically significant. All analyses were conducted with R: A Language and Environment for Statistical Computing, version 4.0 for MacOS (R Foundation for Statistical Computing, Vienna, Austria).<\/p>\n<h2 id=\"_i9\" class=\"article-section__title section__title\">Results<\/h2>\n<p>Overall, 46 countries with complete data were included in the analysis.\u00a0<a class=\"ref showTableEvent\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#tb1\" data-id=\"tb1\">Table 1<\/a> presents a summary of COVID-19 and GDP indicators by quintiles of vitamin D deficiency. The overall median percentage of vitamin D deficiency was 49.0 (IQR 26.8 to 56.6)\u2014from 13.0 (IQR 7.5 to 17.0) in the first quintile to 65.0 (IQR 60.0 to 68.9) in the fifth quintile.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-85291\" src=\"http:\/\/stateofthenation.co\/wp-content\/uploads\/2021\/09\/Screen-Shot-2021-09-21-at-10.40.35-AM.png\" alt=\"\" width=\"392\" height=\"899\" srcset=\"http:\/\/stateofthenation.co\/wp-content\/uploads\/2021\/09\/Screen-Shot-2021-09-21-at-10.40.35-AM.png 392w, http:\/\/stateofthenation.co\/wp-content\/uploads\/2021\/09\/Screen-Shot-2021-09-21-at-10.40.35-AM-131x300.png 131w\" sizes=\"auto, (max-width: 392px) 100vw, 392px\" \/><\/p>\n<p>Note: Critical cases are expressed as a number of cases. Critical case ratio is explained in <a class=\"ref sec\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#s002\">Methods<\/a>\u00a0section. Incidence as expressed is the number of cases\/population of the country. Death rate as expressed is the number of deaths\/population of the country. Case fatality ratio is the number of COVID-19 deaths among COVID cases. Positivity rate is a percentage (positive test\/performed tests). Gross domestic product is expressed in US dollars. Vitamin D deficiency is expressed as a percentage.<\/p>\n<div class=\"tableToggle\">\n<div id=\"tb1\" class=\"article-table-content\">\n<div class=\"tableToggle__table\">\n<div class=\"tableFooter\">\n<div id=\"tf2\" class=\"footnote\">\n<p><sup>a<\/sup>\u2009\u00d7\u20091,000 (eg, median of 37,900 cases among overall countries).<\/p>\n<\/div>\n<div id=\"tf3\" class=\"footnote\">\n<p><sup>b<\/sup>\u2009\u00d7\u200910,000.<\/p>\n<\/div>\n<div id=\"tf4\" class=\"footnote\">\n<p><sup>c<\/sup>\u2009\u00d7\u20091,000,000.<\/p>\n<\/div>\n<div id=\"tf5\" class=\"footnote\">\n<p>Abbreviations: GDP, gross domestic product; IQR, interquartile range.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"tableToggle__image imageTable\"><\/div>\n<\/div>\n<\/div>\n<p>The overall median number of COVID-19 cases was 37,900 (IQR 4,400 to 153,600), with a median incidence rate of 2,221.5 (IQR 330.2 to 4,145.2) cases. The median number of COVID-19 deaths was 900 (IQR 100 to 8,700), with a death rate of 53.0 (IQR 8.0 to 231.0). The median case fatality ratio was 4.1 (IQR 1.4 to 6.1). The median test rate was 46,000 (IQR 20,000 to 106,000) and the positivity rate was 3.6% (IQR 1.1 to 7.3).<\/p>\n<h3 id=\"_i10\" class=\"article-section__title\">Vitamin D Deficiency and COVID-19 Incidence<\/h3>\n<p>There was a positive and statistically significant correlation between the incidence of COVID-19 infection and vitamin D deficiency (<i>R<\/i>\u2009=\u20090.39;\u00a0<i>P<\/i>\u2009=\u2009.0075) (<a id=\"f1R\" class=\"\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#f1\" data-tab=\"pane-pcw-Figures\">Figure 1<\/a>).\u00a0<a id=\"f2R\" class=\"\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#f2\" data-tab=\"pane-pcw-Figures\">Figure 2<\/a>\u00a0and\u00a0<a class=\"ref showTableEvent\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#tb2\" data-id=\"tb2\">Table 2<\/a>\u00a0show the results of Poisson regression models. Incidence rate ratios were positively associated with quintiles of vitamin D deficiency.<\/p>\n<figure id=\"f1\" class=\"article__inlineFigure\"><img decoding=\"async\" class=\"figure__image\" title=\"\" src=\"https:\/\/www.liebertpub.com\/cms\/10.1089\/hs.2020.0137\/asset\/images\/medium\/hs.2020.0137_figure1.jpg\" alt=\"Figure 1.\" data-lg-src=\"\/cms\/10.1089\/hs.2020.0137\/asset\/images\/large\/hs.2020.0137_figure1.jpeg\" \/><figcaption><span class=\"captionLabel\">Figure 1.<\/span>\u00a0Correlation between vitamin D deficiency and COVID-19 indicators.<\/figcaption><\/figure>\n<figure id=\"f2\" class=\"article__inlineFigure\"><img decoding=\"async\" class=\"figure__image\" title=\"\" src=\"https:\/\/www.liebertpub.com\/cms\/10.1089\/hs.2020.0137\/asset\/images\/medium\/hs.2020.0137_figure2.jpg\" alt=\"Figure 2.\" data-lg-src=\"\/cms\/10.1089\/hs.2020.0137\/asset\/images\/large\/hs.2020.0137_figure2.jpeg\" \/><figcaption><span class=\"captionLabel\">Figure 2.<\/span>\u00a0Poisson regression models assessing the association between COVID-19 indicators and vitamin D deficiency quintiles. a\u2009=\u2009<i>P<\/i>\u00a0value &lt; .05; b\u2009=\u2009<i>P<\/i>\u00a0value &lt; .01; c\u2009=\u2009<i>P<\/i>\u00a0value &lt; .001. Abbreviations: IRR, incidence rate ratio; Q, quintile.<\/figcaption><\/figure>\n<div class=\"tableToggle\">\n<div id=\"tb2\" class=\"article-table-content\">\n<div class=\"tableToggle__table\">\n<table class=\"table article-section__table\">\n<caption><span class=\"captionLabel\">Table 2.<\/span>\u00a0Results of Poisson Regression Models for COVID-19 Indicators by Vitamin D Deficiency Quintile<\/caption>\n<thead>\n<tr class=\"colsep0\" valign=\"top\">\n<th class=\"colsep0 rowsep1 align_left\" align=\"left\" valign=\"bottom\">Vitamin D Deficiency Quintiles<\/th>\n<th class=\"colsep0 rowsep1 align_center\" align=\"center\" valign=\"bottom\">IRR (95% CI)<\/th>\n<th class=\"colsep0 rowsep1 align_center last\" align=\"center\" valign=\"bottom\"><i>P<\/i>\u00a0Value<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">Incidence<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\"><\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\"><\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q1 (reference)<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&#8211;<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q2<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.02 (0.99-1.04)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.159<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q3<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.1 (1.08-1.13)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q4<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">2.6 (2.55-2.65)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q5<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.62 (1.59-1.66)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">Positivity ratio<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\"><\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\"><\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q1 (reference)<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&#8211;<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q2<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">2.01 (1.34-3.06)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q3<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.51 (1-2.31)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.052<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q4<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.72 (1.15-2.62)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.010<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q5<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">2.17 (1.48-3.26)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">Case fatality ratio<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\"><\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\"><\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q1 (reference)<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&#8211;<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q2<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.05 (0.57-1.91)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.871<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q3<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">2.09 (1.32-3.42)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.002<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q4<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.55 (0.94-2.61)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.093<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q5<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">2.18 (1.36-3.59)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">.002<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">Death rate<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\"><\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\"><\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q1 (reference)<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&#8211;<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q2<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">0.59 (0.52-0.66)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q3<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.74 (1.6-1.89)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0\" valign=\"top\">\n<td class=\"colsep0 rowsep0 align_left\" align=\"left\" valign=\"bottom\">\u2003Q4<\/td>\n<td class=\"colsep0 rowsep0 align_center\" align=\"center\" valign=\"bottom\">1.65 (1.52-1.8)<\/td>\n<td class=\"colsep0 rowsep0 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<tr class=\"colsep0 last\" valign=\"top\">\n<td class=\"colsep0 rowsep1 align_left\" align=\"left\" valign=\"bottom\">\u2003Q5<\/td>\n<td class=\"colsep0 rowsep1 align_center\" align=\"center\" valign=\"bottom\">1.6 (1.47-1.74)<\/td>\n<td class=\"colsep0 rowsep1 align_center last\" align=\"center\" valign=\"bottom\">&lt; .001<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<div class=\"tableFooter\">\n<div id=\"tf6\" class=\"footnote\">\n<p>All models were adjusted for GDP using log transformation<\/p>\n<\/div>\n<div id=\"tf7\" class=\"footnote\">\n<p>Abbreviations: CI, confidence interval; GDP, gross domestic product; IRR, incidence rate ratio; Q, quintile.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"tableToggle__image imageTable\"><\/div>\n<\/div>\n<\/div>\n<h3 id=\"_i13\" class=\"article-section__title\">Vitamin D Deficiency and COVID-19 Positivity<\/h3>\n<p>There was a positive correlation (<i>R<\/i>\u2009=\u20090.36;\u00a0<i>P<\/i>\u2009=\u2009.016) between vitamin D deficiency and the positivity ratio (<a id=\"f1R\" class=\"\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#f1\" data-tab=\"pane-pcw-Figures\">Figure 1<\/a>). In Poisson regression models (adjusted for GDP), the association between the positivity ratio and vitamin D deficiency was evident and the relationships were strongest for the second quintile (IRR 2.01; 95% CI, 1.34 to 3.06;\u00a0<i>P<\/i>\u2009=\u2009.001), the fourth quintile (IRR 1.72; 95% CI, 1.15 to 2.62;\u00a0<i>P<\/i>\u2009&lt;\u2009.010) and the fifth quintile (IRR 2.17; 95% CI, 1.48 to 3.26;\u00a0<i>P<\/i>\u2009&lt;\u2009.001) (<a id=\"f2R\" class=\"\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#f2\" data-tab=\"pane-pcw-Figures\">Figure 2<\/a>,\u00a0<a class=\"ref showTableEvent\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#tb2\" data-id=\"tb2\">Table 2<\/a>).<\/p>\n<h3 id=\"_i14\" class=\"article-section__title\">Vitamin D Deficiency and Case Fatality Ratio and Death Rate<\/h3>\n<p>There were positive and statistically significant correlations between vitamin D deficiency and the case fatality ratio (<i>R<\/i>\u2009=\u20090.40;\u00a0<i>P<\/i>\u2009=\u2009.007) and death rate (<i>R<\/i>\u2009=\u20090.38;\u00a0<i>P<\/i>\u2009=\u2009.011) (<a id=\"f1R\" class=\"\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#f1\" data-tab=\"pane-pcw-Figures\">Figure 1<\/a>). For the case fatality ratio, the IRR in the fifth quintile was more than double the IRR in the first quintile, after adjusting for GDP. The death rate was higher in the third, fourth, and fifth quintiles (<a id=\"f2R\" class=\"\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#f2\" data-tab=\"pane-pcw-Figures\">Figure 2<\/a>,\u00a0<a class=\"ref showTableEvent\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#tb2\" data-id=\"tb2\">Table 2<\/a>).<\/p>\n<h2 id=\"_i15\" class=\"article-section__title section__title\">Discussion<\/h2>\n<p>The results of the present study suggest an association at the population level between the prevalence of vitamin D deficiency and the risk of being infected with COVID-19, severity of the disease, and risk of dying from it. These associations were consistent in both correlation analyses and Poisson regression models adjusted for GDP (the indicator for socioeconomic level). This study extends those observations by quantifying the association between incidence and severity of COVID-19 and documenting the association with the case fatality ratio. A strength of this study is the inclusion and analysis of information from 46 countries around the world.<\/p>\n<p>A 2010 study showed that people with a mean serum 25(OH)D concentration level of more than 38\u2009ng\/mL\u2014over a period of 4 to 5 months during fall and winter\u2014had less than half the incidence rate of acute viral respiratory infections seen in those with lower concentrations.<sup><a id=\"B23R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B23\" data-tab=\"pane-pcw-references\">23<\/a><\/sup>\u00a0Another ecological study found that communities exposed to higher solar ultraviolet type B radiation doses\u2014both in summer and in winter\u2014had a significantly lower case fatality rate during the 1918-1919 influenza pandemic in the United States.<sup><a id=\"B24R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B24\" data-tab=\"pane-pcw-references\">24<\/a><\/sup>\u00a0One study in South Korea found that a serum 25(OH)D concentration of more than 20\u2009ng\/mL was associated with an adjusted odds ratio for mortality of 0.94 (95% CI, 0.90 to 0.99) for those who developed community-acquired pneumonia.<sup><a id=\"B25R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B25\" data-tab=\"pane-pcw-references\">25<\/a><\/sup><\/p>\n<p>Evidence suggests that vitamin D could play a protective role against COVID-19 infection. A 2020 review of evidence<sup><a id=\"B26R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B26\" data-tab=\"pane-pcw-references\">26<\/a><\/sup>\u00a0included the following as evidence supporting the protective role of vitamin D: the occurrence of outbreaks during the winter (when serum levels of vitamin D are lowest), the low number of cases observed in the southern hemisphere near the end of summer, the association between vitamin D deficiency and the development of acute respiratory distress syndrome, and that mortality rates increase in older adults and in patients with chronic diseases (both age and chronic disease comorbidity are associated with reduced serum 25(OH)D concentrations). It has been suggested that a strong correlation exists between latitude, which directly influences a person&#8217;s exposure to sunlight, and mortality following COVID-19 infection.<sup><a id=\"B27R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B27\" data-tab=\"pane-pcw-references\">27<\/a>,<a id=\"B28R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B28\" data-tab=\"pane-pcw-references\">28<\/a><\/sup>\u00a0Low mortality rates observed in Nordic countries are exceptions that could be explained by strong supplementation and food fortification with vitamin D carried out in these countries.<sup><a id=\"B29R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B29\" data-tab=\"pane-pcw-references\">29<\/a><\/sup>\u00a0Epidemiological studies in Europe and the United States have also suggested an inverse relationship between vitamin D levels and COVID-19 risk.<sup><a id=\"B30R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B30\" data-tab=\"pane-pcw-references\">30<\/a>,<a id=\"B31R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B31\" data-tab=\"pane-pcw-references\">31<\/a><\/sup>\u00a0Vitamin D supplementation has consistently been considered useful in the treatment of COVID-19 infection.<sup><a id=\"B32R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B32\" data-tab=\"pane-pcw-references\">32<\/a><\/sup><\/p>\n<p>Furthermore, a 2020 study determined that vitamin D may interfere with the functionality of 70% of SARS-CoV-2 proteins through alteration of the expression of 25% of human genes encoding protein targets of SARS-CoV-2.\u00a0<sup><a id=\"B33R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B33\" data-tab=\"pane-pcw-references\">33<\/a><\/sup>\u00a0Deficiency in vitamin D would, therefore, contribute to susceptibility to infection and morbidity and mortality due to COVID-19. It has also been reported that one of the main defenses against uncontrolled inflammation, especially of viral origin, is represented by regulatory T cells. Many patients with COVID-19 have been found to have reduced levels of regulatory T cells, which may be increased by supplementation with vitamin D.<sup><a id=\"B34R\" class=\"tab-link\" href=\"https:\/\/www.liebertpub.com\/doi\/full\/10.1089\/hs.2020.0137?_se=YW5kcmV3Lnlhc2hjaHVrQGdtYWlsLmNvbQ%3D%3D#B34\" data-tab=\"pane-pcw-references\">34<\/a><\/sup><\/p>\n<h3 id=\"_i16\" class=\"article-section__title\">Limitations<\/h3>\n<p>This study has several limitations that are important to consider when interpreting the results. Because it is an ecological study, the results do not mean that individuals with vitamin D deficiency are at increased risk of COVID-19 infection and mortality (this would be an ecological fallacy). However, evidence from observational studies suggest that the relationship between COVID-19 risk and mortality remains at the level of the individual participants.<\/p>\n<p>Because the number of countries included in our analysis was determined by the countries with available population estimates for 25(OH)D deficiency identified in our search, we acknowledge that the inclusion of all countries with reported COVID-19 data could change the results. However, as discussed previously, observations from other studies with different designs are consistent with our results.<\/p>\n<h2 id=\"_i17\" class=\"article-section__title section__title\">Conclusion<\/h2>\n<p>The results of the present study suggest that vitamin D deficiency as associated with an increased risk of COVID-19 infection and mortality across a wide range of countries. Since the accumulating body of evidence strongly suggests the risks of vitamin D deficiency and the benefits of vitamin D supplementation, there is an urgent need for evidence from well-designed clinical trials evaluating vitamin D supplementation for the prevention and treatment of COVID-19 in different settings.<\/p>\n<div class=\"ack\">\n<h2 id=\"_i18\" class=\"article-section__title section__title\">Acknowledgments<\/h2>\n<p>This work was supported by grants from the Research and Technology Council of Cuyo University (SECyT), Mendoza, Argentina (grant no. (PICT 2016-4541), and from the National Agency for Scientific and Technological Promotion (ANPCYT) through the Scientific and Technological Research Fund (FONCYT; grant no. IP-COVID-19-931), both of which were awarded to Walter Manucha.<\/p>\n<\/div>\n<h2 id=\"_i20\" class=\"article-section__title section__title\"><\/h2>\n<p><sup>*<\/sup>\u00a0Serum 25(OH)D levels are also measured using nanomoles per liter. The vitamin D deficiency threshold of 20\u2009ng\/mL is equalivent to 50\u2009nmol\/L.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-85288","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"http:\/\/stateofthenation.co\/index.php?rest_route=\/wp\/v2\/posts\/85288","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/stateofthenation.co\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/stateofthenation.co\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/stateofthenation.co\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/stateofthenation.co\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=85288"}],"version-history":[{"count":0,"href":"http:\/\/stateofthenation.co\/index.php?rest_route=\/wp\/v2\/posts\/85288\/revisions"}],"wp:attachment":[{"href":"http:\/\/stateofthenation.co\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=85288"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/stateofthenation.co\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=85288"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/stateofthenation.co\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=85288"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}