Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach
MD, MSc Dimitrios T Papadimitriou, Alexandros K Vassaras, Michael F Holick
World Journal of Virology, doi:10.5501/wjv.v10.i3.111
BACKGROUND Vitamin D population status may have possible unappreciated consequences to the coronavirus disease 2019 (COVID-19) pandemic. Α significant association between vitamin D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease has recently been shown, while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Low serum 25-hydroxyvitamin-D [25(OH)D] was identified as an independent risk factor for COVID-19 infection and hospitalization, and administration of 0.532 mg (21280 IU) of calcifediol or 25(OH)D, followed by 0.266 mg on days 3 and 7 and then weekly until discharge or intensive care unit admission significantly reduced the need for intensive care unit treatment. AIM To elucidate the role of vitamin D European population status in the COVID-19 pandemic, data from the Worldometer were analyzed.
Research motivation Vitamin D population status may indeed have possible unappreciated consequences to the COVID-19 pandemic, a hypothesis that needed to be further elucidated.
Research objectives Following an ecological integrative approach, we examined the associations between published representative and standardized European population vitamin D data and the Worldometer COVID-19 data at two completely different time points of the first wave of this pandemic. If any sustained correlations were to be found, they would be an indication of a truthful association, even though they could not prove causality.
Research methods Using linear regression, we explored the correlation between published representative and standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19 for 26 European countries populated > 4 M. Life expectancy (LE) was also analyzed with semi-parametric regression. Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status: deficient < 50, insufficient: 50-62.5, mildly insufficient > 62.5-75 and sufficient > 75 nmol/L, while controlling for LE for deaths/M. Statistical analyses were performed in XLSTAT LIFE SCIENCE and R (SemiPar library).
Research results No correlation was found between population vitamin D concentrations and the total cases-recovered/M, but negative..
References
Avenell, Mak, Connell, Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men, Cochrane Database Syst Rev,
doi:10.1002/14651858.CD000227.pub4Bettencourt, Boleixa, Reis, Oliveira, Mendonça et al., Serum 25-hydroxyvitamin D levels in a healthy population from the North of Portugal, J Steroid Biochem Mol Biol,
doi:10.1016/j.jsbmb.2016.11.005Bolland, Grey, Avenell, Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(18)30265-1Bone, Society, Vitamin D and health in adults in Australia and New Zealand: a position statement, Med J Aust,
doi:10.5694/mja11.10301Caccialanza, Laviano, Lobascio, Montagna, Bruno et al., Early nutritional supplementation in non-critically ill patients hospitalized for the 2019 novel coronavirus disease (COVID-19): Rationale and feasibility of a shared pragmatic protocol, Nutrition,
doi:10.1016/j.nut.2020.110835Calder, Carr, Gombart, Eggersdorfer, Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections, Nutrients,
doi:10.3390/nu12041181Cashman, Dowling, Škrabáková, Gonzalez-Gross, Valtueña et al., Vitamin D deficiency in Europe: pandemic?, Am J Clin Nutr,
doi:10.3945/ajcn.115.120873Castillo, Costa, Barrios, Díaz, Miranda et al., Effect of calcifediol treatment and best available therapy vs best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J Steroid Biochem Mol Biol,
doi:10.1016/j.jsbmb.2020.105751Cesareo, Iozzino, 'onofrio, Terrinoni, Maddaloni et al., Effectiveness and safety of calcium and vitamin D treatment for postmenopausal osteoporosis, Minerva Endocrinol
D'avolio, Avataneo, Manca, Cusato, Nicolò et al., 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2, Nutrients,
doi:10.3390/nu12051359Dancer, Parekh, Lax, Souza, Zheng et al., Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS), Thorax,
doi:10.1136/thoraxjnl-2014-206680Daneshkhah, Agrawal, Eshein, Subramanian, Roy et al., The Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients, MedRxiv,
doi:10.1101/2020.04.08.20058578De Groot, Verheijden, De Henauw, Schroll, Van Staveren et al., Lifestyle, nutritional status, health, and mortality in elderly people across Europe: a review of the longitudinal results of the SENECA study, J Gerontol A Biol Sci Med Sci,
doi:10.1093/gerona/59.12.1277Devaux, Rolain, Raoult, ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome, J Microbiol Immunol Infect,
doi:10.1016/j.jmii.2020.04.015Ekwaru, Zwicker, Holick, Giovannucci, Veugelers, The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers, PLoS One,
doi:10.1371/journal.pone.0111265Elmadfa, Meyer, Wottawa, Wagner, Hasenegger, Vitamin D intake and status in Austria and its effects on some health indicators, Austin J Nutr Metab
Garland, Kim, Mohr, Gorham, Grant et al., Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D, Am J Public Health,
doi:10.2105/AJPH.2014.302034Ginde, Brower, Caterino, Finck, Banner-Goodspeed et al., and Blood Institute PETAL Clinical Trials Network. Early High-Dose Vitamin D 3 for Critically Ill, Vitamin D-Deficient Patients, N Engl J Med,
doi:10.1056/NEJMoa1911124Grant, Giovannucci, The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918-1919 influenza pandemic in the United States, Dermatoendocrinol,
doi:10.4161/derm.1.4.9063Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients,
doi:10.3390/nu12040988Heaney, Garland, Baggerly, French, Gorham et al., A statistical error in the estimation of the recommended dietary allowance for vitamin D, Nutrients,
doi:10.3390/nu7031688Hilger, Friedel, Herr, Rausch, Roos et al., A systematic review of vitamin D status in populations worldwide, Br J Nutr,
doi:10.1017/S0007114513001840Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res,
doi:10.1007/s40520-020-01570-8Kara, Ekiz, Ricci, Kara, Chang et al., Scientific Strabismus' or two related pandemics: coronavirus disease and vitamin D deficiency, Br J Nutr,
doi:10.1017/S0007114520001749Koivisto, Hanel, Carlberg, Key Vitamin D Target Genes with Functions in the Immune System, Nutrients,
doi:10.3390/nu12041140Lips, Cashman, Lamberg-Allardt, Bischoff-Ferrari, Obermayer-Pietsch et al., Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society, Eur J Endocrinol,
doi:10.1530/EJE-18-0736Madden, Feldman, Chun, Smith, Sullivan et al., Critically Ill Children Have Low Vitamin D-Binding Protein, Influencing Bioavailability of Vitamin D, Ann Am Thorac Soc,
doi:10.1513/AnnalsATS.201503-160OCMaghbooli, Sahraian, Ebrahimi, Pazoki, Kafan et al., Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection, PLoS One,
doi:10.1371/journal.pone.0239799Manios, Moschonis, Lambrinou, Tsoutsoulopoulou, Binou et al., A systematic review of vitamin D status in southern European countries, Eur J Nutr,
doi:10.1007/s00394-017-1564-2Manson, Brannon, Rosen, Taylor, Vitamin D Deficiency -Is There Really a Pandemic?, N Engl J Med,
doi:10.1056/NEJMp1608005Manson, Cook, Lee, Bassuk, Mora et al., Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease, N Engl J Med,
doi:10.1056/NEJMoa1809944Martens, Gysemans, Verstuyf, Mathieu, Vitamin D's Effect on Immune Function, Nutrients,
doi:10.3390/nu12051248Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ,
doi:10.1136/bmj.i6583Mccartney, Byrne, Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19, Ir Med J
Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, JAMA Netw Open,
doi:10.1001/jamanetworkopen.2020.19722Merzon, Tworowski, Gorohovski, Vinker, Cohen et al., Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study, FEBS J,
doi:10.1111/febs.15495Munns, Shaw, Kiely, Specker, Thacher et al., Global Consensus Recommendations on Prevention and Management of Nutritional Rickets, J Clin Endocrinol Metab,
doi:10.1210/jc.2015-2175Napoli, Strollo, Sprini, Maddaloni, Rini, Serum 25-OH Vitamin D in relation to Bone Mineral Density and Bone Turnover, Int J Endocrinol,
doi:10.1155/2014/487463Nowson, Mcgrath, Ebeling, Haikerwal, Daly et al., None
Plos One Editors, Expression of Concern: Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection, PLoS One,
doi:10.1371/journal.pone.0240965Rhodes, Subramanian, Laird, Kenny, Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity, Aliment Pharmacol Ther,
doi:10.1111/apt.15777Rondanelli, Miccono, Lamburghini, Avanzato, Riva et al., Self-Care for Common Colds: The Pivotal Role of Vitamin D, Vitamin C, Zinc, and Echinacea in Three Main Immune Interactive Clusters (Physical Barriers, Innate and Adaptive Immunity) Involved during an Episode of Common Colds-Practical Advice on Dosages and on the Time to Take These Nutrients/Botanicals in order to Prevent or Treat Common Colds, Evid Based Complement Alternat Med,
doi:10.1155/2018/5813095Sempos, Heijboer, Bikle, Bollerslev, Bouillon et al., Vitamin D assays and the definition of hypovitaminosis D: results from the First International Conference on Controversies in Vitamin D, Br J Clin Pharmacol,
doi:10.1111/bcp.13652Shirvani, Kalajian, Song, Holick, Disassociation of Vitamin D's Calcemic Activity and Non-calcemic Genomic Activity and Individual Responsiveness: A Randomized Controlled Double-Blind Clinical Trial, Sci Rep,
doi:10.1038/s41598-019-53864-1Somasundaram, Ranathunga, Ratnasamy, Wijewickrama, Dissanayake et al., The Impact of SARS-Cov-2 Virus Infection on the Endocrine System, J Endocr Soc,
doi:10.1210/jendso/bvaa082Telcian, Zdrenghea, Edwards, Laza-Stanca, Mallia et al., Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro, Antiviral Res,
doi:10.1016/j.antiviral.2016.11.004Tramontana, Napoli, El-Hajj Fuleihan, Strollo, The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond, Endocrine,
doi:10.1007/s12020-020-02407-0Van Der Wielen, Löwik, Van Den Berg, De Groot, Haller et al., Serum vitamin D concentrations among elderly people in Europe, Lancet,
doi:10.1016/s0140-6736(95)91266-5Veugelers, Ekwaru, A statistical error in the estimation of the recommended dietary allowance for vitamin D, Nutrients,
doi:10.3390/nu6104472Vidovic, Faid, Pantovic, Nikolic, Debeljak-Martacic et al., Vitamin D and cardio-metabolic biomarkers: small-scale comparative study between Libyan migrants and resident women in Serbia, Libyan J Med,
doi:10.1080/19932820.2019.1622364Vojdeman, Madsen, Frederiksen, Durup, Olsen et al., Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark, Int J Cancer,
doi:10.1002/ijc.32105Wacker, Holick, Vitamin D -effects on skeletal and extraskeletal health and the need for supplementation, Nutrients,
doi:10.3390/nu5010111Wang, Hu, Hu, Zhu, Liu et al., Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China, JAMA,
doi:10.1001/jama.2020.1585Weaver, Alexander, Boushey, Dawson-Hughes, Lappe et al., Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation, Osteoporos Int,
doi:10.1007/s00198-015-3386-5Zhang, Fang, Tang, Jia, Feng et al., Association between vitamin D supplementation and mortality: systematic review and meta-analysis, BMJ,
doi:10.1136/bmj.l4673Zhou, Dong, Kim, Choi, Sun et al., Vitamin D Receptor Activation in Liver Macrophages Protects Against Hepatic Endoplasmic Reticulum Stress in Mice, Hepatology,
doi:10.1002/hep.30887
