Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths
William B Grant, Henry Lahore, Sharon L Mcdonnell, Carole A Baggerly, Christine B French, Jennifer L Aliano, Harjit P Bhattoa
Nutrients, doi:10.3390/nu12040988
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 D 3 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 D 3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
References
Adams, Ren, Liu, Chun, Lagishetty et al., Vitamin d-directed rheostatic regulation of monocyte antibacterial responses, J. Immunol,
doi:10.4049/jimmunol.0803736
Alvarez, Aguilar-Jimenez, Rugeles, The Potential Protective Role of Vitamin D Supplementation on HIV-1 Infection, Front. Immunol,
doi:10.3389/fimmu.2019.02291
Amir, Simmons, Freedman, Dranitsaris, Cole et al., A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases, Cancer,
doi:10.1002/cncr.24749
Amrein, Papinutti, Mathew, Vila, Parekh, Vitamin D and critical illness: What endocrinology can learn from intensive care and vice versa, Endocr. Connect,
doi:10.1530/EC-18-0184
Amrein, Scherkl, Hoffmann, Neuwersch-Sommeregger, Kostenberger et al., deficiency 2.0: An update on the current status worldwide, Eur. J. Clin. Nutr,
doi:10.1038/s41430-020-0558-y
Aparicio-Ugarriza, Salguero, Mohammed, Ferri-Guerra, Baskaran et al., Is vitamin D deficiency related to a higher risk of hospitalization and mortality in veterans with heart failure?, Maturitas,
doi:10.1016/j.maturitas.2019.11.005
Arboleda, Urcuqui-Inchima, Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection?, Adv. Virol,
doi:10.1155/2016/1016840
Arihiro, Nakashima, Matsuoka, Suto, Uchiyama et al., Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza and Upper Respiratory Infection in Patients With Inflammatory Bowel Disease, Inflamm. Bowel Dis,
doi:10.1093/ibd/izy346
Assiri, Mcgeer, Perl, Price, Al Rabeeah et al., Hospital outbreak of Middle East respiratory syndrome coronavirus, N. Engl. J. Med,
doi:10.1056/NEJMoa1306742
Autier, Mullie, Macacu, Dragomir, Boniol et al., Effect of vitamin D supplementation on non-skeletal disorders: A systematic review of meta-analyses and randomised trials, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(17)30357-1
Barlow, Svoboda, Mackellar, Nash, York et al., Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37, PLoS ONE,
doi:10.1371/journal.pone.0025333
Brice, Toth, Diamond, LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells, Antivir. Res,
doi:10.1016/j.antiviral.2018.07.025
Brot, Jorgensen, Sorensen, The influence of smoking on vitamin D status and calcium metabolism, Eur. J. Clin. Nutr,
doi:10.1038/sj.ejcn.1600870
Bucak, Ozturk, Almis, Cevik, Tekin et al., Is there a relationship between low vitamin D and rotaviral diarrhea?, Pediatr. Int,
doi:10.1111/ped.12809
Camargo, Jr, Ganmaa, Frazier, Kirchberg et al., Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia, Pediatrics,
doi:10.1542/peds.2011-3029
Cantorna, Snyder, Lin, Yang, Vitamin D and 1,25(OH)2D regulation of T cells, Nutrients,
doi:10.3390/nu7043011
Charoenngam, Shirvani, Kalajian, Song, Holick, The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study, Anticancer Res,
doi:10.21873/anticanres.13984
Chen, Leng, Lu, Wen, Qi et al., Epidemiological features and time-series analysis of influenza incidence in urban and rural areas of Shenyang, China, 2010-2018, Epidemiol. Infect,
doi:10.1017/S0950268820000151
Chen, Wu, Wang, Shi, Shen et al., Association Between 25-Hydroxyvitamin D and Epicardial Adipose Tissue in Chinese Non-Obese Patients with Type 2 Diabetes, Med. Sci. Monit,
doi:10.12659/MSM.904755
Cho, Shaw, Karuranga, Huang, Da Rocha Fernandes et al., IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045, Diabetes Res. Clin. Pract,
doi:10.1016/j.diabres.2018.02.023
Christensen, Lien, Hustad, Almas, Seasonal and age-related differences in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in patients from Western Norway, Scand. J. Clin. Lab. Invest,
doi:10.3109/00365511003797172
Cianferotti, Bertoldo, Bischoff-Ferrari, Bruyere, Cooper et al., Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: Research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO), Endocrine,
doi:10.1007/s12020-017-1290-9
Clay, Lewis, Severnini, What explains cross-city variation in mortality during the 1918 influenza pandemic? Evidence from 438 U.S. cities, Econ. Hum. Biol,
doi:10.1016/j.ehb.2019.03.010
Coussens, The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease, Photochem. Photobiol. Sci,
doi:10.1039/c6pp00355a
Croft, Zhang, Lin, Thurston, Hopke et al., Associations between Source-Specific Particulate Matter and Respiratory Infections in New York State Adults, Environ. Sci. Technol,
doi:10.1021/acs.est.9b04295
Currie, Findlay, Mchugh, Mackellar, Man et al., The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus, PLoS ONE,
doi:10.1371/journal.pone.0073659
Dalvi, Ramraje, Patil, Hegde, Yeram, Study of IL-6 and vitamin D3 in patients of pulmonary tuberculosis, Indian J. Tuberc,
doi:10.1016/j.ijtb.2018.05.018
Dancer, Parekh, Lax, D'souza, Zheng et al., Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS), Thorax,
doi:10.1136/thoraxjnl-2014-206680
Ekwaru, 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.0111265
Fan, Zhang, Tian, Zhong, Wu et al., CYP24A1 genetic variants in the vitamin D metabolic pathway are involved in the outcomes of hepatitis C virus infection among high-risk Chinese population, Int. J. Infect. Dis,
doi:10.1016/j.ijid.2019.04.032
Feigenbaum, Muller, Wrigley-Field, Regional and Racial Inequality in Infectious Disease Mortality in U.S. Cities, Demography,
doi:10.1007/s13524-019-00789-z
Feng, Guo, Wang, Kang, Che et al., The vitamin D status and its effects on life quality among the elderly in Jinan, China, Arch. Gerontol. Geriatr,
doi:10.1016/j.archger.2015.09.002
Gholami, Moradi, Zareei, Rasouli, Nikkhoo et al., The association between circulating 25-hydroxyvitamin D and cardiovascular diseases: A meta-analysis of prospective cohort studies, BMC Cardiovasc. Disord,
doi:10.1186/s12872-019-1236-7
Ginde, Liu, Camargo, Jr, Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004, Arch. Intern. Med,
doi:10.1001/archinternmed.2008.604
Gombart, Pierre, Maggini, A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection, Nutrients,
doi:10.3390/nu12010236
Grant, Al Anouti, Moukayed, Targeted 25-hydroxyvitamin D concentration measurements and vitamin D3 supplementation can have important patient and public health benefits, Eur. J. Clin. Nutr
Grant, Boucher, A Review of the Potential Benefits of Increasing Vitamin D Status in Mongolian Adults through Food Fortification and Vitamin D Supplementation, Nutrients,
doi:10.3390/nu11102452
Grant, Boucher, Bhattoa, Lahore, Why vitamin D clinical trials should be based on 25-hydroxyvitamin D concentrations, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2017.08.009
Grant, Fakhoury, Karras, Al Anouti, Bhattoa, Variations in 25-Hydroxyvitamin D in Countries from the Middle East and Europe: The Roles of UVB Exposure and Diet, Nutrients,
doi:10.3390/nu11092065
Grant, 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.1.4.9063
Grant, Karras, Bischoff-Ferrari, Annweiler, Boucher et al., Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects?, Derm. Endocrinol,
doi:10.1080/19381980.2016.1187349
Greiller, Martineau, Modulation of the immune response to respiratory viruses by vitamin D, Nutrients,
doi:10.3390/nu7064240
Grober, Kisters, Influence of drugs on vitamin D and calcium metabolism, Dermatoendocrinol,
doi:10.4161/derm.20731
Gui, Chen, Hu, Zhu, He, Effects of calcitriol (1, 25-dihydroxy-vitamin D3) on the inflammatory response induced by H9N2 influenza virus infection in human lung A549 epithelial cells and in mice, Virol. J,
doi:10.1186/s12985-017-0683-y
Hagel, Ludewig, Moeser, Baier, Loffler et al., Characteristics and management of patients with influenza in a German hospital during the 2014/2015 influenza season, Infection,
doi:10.1007/s15010-016-0920-0
Han, Jones, Tangpricha, Brown, Brown et al., High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial, J. Clin. Transl. Endocrinol,
doi:10.1016/j.jcte.2016.04.004
He, Gu, Zhang, Spatiotemporal trends of PM2.5 concentrations in central China from 2003 to 2018 based on MAIAC-derived high-resolution data, Environ. Int,
doi:10.1016/j.envint.2020.105536
Heaney, Davies, Chen, Holick, Barger-Lux, Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol, Am. J. Clin. Nutr,
doi:10.1093/ajcn/77.1.204
Heaney, Guidelines for optimizing design and analysis of clinical studies of nutrient effects, Nutr. Rev,
doi:10.1111/nure.12090
Henley, Gallaway, Singh, O'neil, Buchanan Lunsford et al., Lung Cancer Among Women in the United States, J. Womens Health,
doi:10.1089/jwh.2018.7397
Herr, Shaykhiev, Bals, The role of cathelicidin and defensins in pulmonary inflammatory diseases, Expert Opin. Biol. Ther,
doi:10.1517/14712598.7.9.1449
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2011-0385
Hoseinzadeh, Taha, Wei, Godini, Ashraf et al., The impact of air pollutants, UV exposure and geographic location on vitamin D deficiency, Food Chem. Toxicol
Hou, Zhao, Liu, Impact of serum 25-hydroxyvitamin D on cardiac prognosis in Chinese patients with heart failure, Br. J. Nutr,
doi:10.1017/S0007114519000795
Hu, Wang, Jiang, Li, Guo et al., Low vitamin D levels are associated with high viral loads in patients with chronic hepatitis B: A systematic review and meta-analysis, BMC Gastroenterol,
doi:10.1186/s12876-019-1004-2
Jeffery, Burke, Mura, Zheng, Qureshi et al., 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3, J. Immunol,
doi:10.4049/jimmunol.0803217
Kast, Mcfarlane, Globinska, Sokolowska, Wawrzyniak et al., Respiratory syncytial virus infection influences tight junction integrity, Clin. Exp. Immunol,
doi:10.1111/cei.13042
Kim, Jang, Hong, Park, Choi, Relationship between serum vitamin D concentrations and clinical outcome of community-acquired pneumonia, Int. J. Tuberc. Lung Dis
Kroll, Bi, Garber, Kaufman, Liu et al., Temporal relationship between vitamin D status and parathyroid hormone in the United States, PLoS ONE,
doi:10.1371/journal.pone.0118108
Lappe, Watson, Travers-Gustafson, Recker, Garland et al., Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial, JAMA,
doi:10.1001/jama.2017.2115
Laviano, Sanchez Rubio, Gonzalez-Nicolas, Palacian, Lopez et al., Association between preoperative levels of 25-hydroxyvitamin D and hospital-acquired infections after hepatobiliary surgery: A prospective study in a third-level hospital, PLoS ONE,
doi:10.1371/journal.pone.0230336
Lei, Zhang, Cheng, Lee, Mechanisms of Action of Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia, Antimicrob. Agents Chemother,
doi:10.1128/AAC.01226-17
Lemire, Adams, Kermani-Arab, Bakke, Sakai et al., 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro, J. Immunol
Li, Ding, Serum 25-Hydroxyvitamin D and the risk of mortality in adult patients with Sepsis: A meta-analysis, BMC Infect. Dis,
doi:10.1186/s12879-020-4879-1
Liu, Li, Qin, Zhu, Li et al., Effects of air pollutants on occurrences of influenza-like illness and laboratory-confirmed influenza in Hefei, China, Int. J. Biometeorol,
doi:10.1007/s00484-018-1633-0
Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science,
doi:10.1126/science.1123933
Loeb, Dang, Thiem, Thanabalan, Wang et al., Effect of Vitamin D supplementation to reduce respiratory infections in children and adolescents in Vietnam: A randomized controlled trial. Influenza Other, Respir. Viruses,
doi:10.1111/irv.12615
Longhin, Holme, Gualtieri, Camatini, Ovrevik, Milan winter fine particulate matter (wPM2.5) induces IL-6 and IL-8 synthesis in human bronchial BEAS-2B cells, but specifically impairs IL-8 release, Toxicol. In Vitro,
doi:10.1016/j.tiv.2018.07.016
Lu, Zhang, Ma, Yue, Zou et al., Link between community-acquired pneumonia and vitamin D levels in older patients, Z. Gerontol. Geriatr,
doi:10.1007/s00391-017-1237-z
Lucato, Solmi, Maggi, Bertocco, Bano et al., Low vitamin D levels increase the risk of type 2 diabetes in older adults: A systematic review and meta-analysis, Maturitas,
doi:10.1016/j.maturitas.2017.02.016
Maclaughlin, Holick, Aging decreases the capacity of human skin to produce vitamin D3, J. Clin. Invest,
doi:10.1172/JCI112134
Mahallawi, Khabour, Zhang, Makhdoum, Suliman, MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile, Cytokine,
doi:10.1016/j.cyto.2018.01.025
Malihi, Lawes, Wu, Huang, Waayer et al., Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: Results from a randomized controlled trial, Am. J. Clin. Nutr,
doi:10.1093/ajcn/nqy378
Malinovschi, Masoero, Bellocchia, Ciuffreda, Solidoro et al., Severe vitamin D deficiency is associated with frequent exacerbations and hospitalization in COPD patients, Respir. Res,
doi:10.1186/s12931-014-0131-0
Manion, Hullsiek, Wilson, Rhame, Kojic et al., Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons, PLoS ONE,
doi:10.1371/journal.pone.0175517
Manson, Cook, Lee, Christen, Bassuk et al., Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease, N. Engl. J. Med,
doi:10.1056/NEJMoa1809944
Martineau, 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.i6583
Martinez-Moreno, Hernandez, Urcuqui-Inchima, Effect of high doses of vitamin D supplementation on dengue virus replication, Toll-like receptor expression, and cytokine profiles on dendritic cells, Mol. Cell. Biochem,
doi:10.1007/s11010-019-03658-w
Mccullough, Lehrer, Amend, Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2018.12.010
Mcdonnell, Baggerly, French, Heaney, Gorham et al., Incidence rate of type 2 diabetes is >50% lower in GrassrootsHealth cohort with median serum 25-hydroxyvitamin D of 41 ng/mL than in NHANES cohort with median of 22 ng/mL, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2015.06.013
Mirzavandi, Talenezhad, Razmpoosh, Nadjarzadeh, Mozaffari-Khosravi, The effect of intramuscular megadose of vitamin D injections on E-selectin, CRP and biochemical parameters in vitamin D-deficient patients with type-2 diabetes mellitus: A randomized controlled trial, Complement. Ther. Med,
doi:10.1016/j.ctim.2020.102346
Moura, Perdigao, Siqueira, Seasonality of influenza in the tropics: A distinct pattern in northeastern Brazil, Am. J. Trop. Med. Hyg,
doi:10.4269/ajtmh.2009.81.180
Mousavi, Bereswill, Heimesaat, Immunomodulatory and Antimicrobial Effects of Vitamin C, Eur. J. Microbiol. Immunol,
doi:10.1556/1886.2019.00016
Naghshtabrizi, Borzouei, Bigvand, Seifrabiei, Evaluation of the Relationship between Serum 25-Hydroxy Vitamin D and Hypertension in Hamadan, Iran-A Case Control Study, J. Clin. Diagn. Res,
doi:10.7860/JCDR/2017/25522.10187
Nassar, Bakhrebah, Meo, Alsuabeyl, Zaher, Global seasonal occurrence of middle east respiratory syndrome coronavirus (MERS-CoV) infection, Eur. Rev. Med. Pharmacol. Sci,
doi:10.26355/eurrev_201806_15276
Paget, Spreeuwenberg, Charu, Taylor, Iuliano et al., Global mortality associated with seasonal influenza epidemics: New burden estimates and predictors from the GLaMOR Project, J. Glob. Health,
doi:10.7189/jogh.09.020421
Paynter, Ware, Sly, Weinstein, Williams, Respiratory syncytial virus seasonality in tropical Australia, Aust. N. Z. J. Public Health,
doi:10.1111/1753-6405.12347
Pilz, Marz, Cashman, Kiely, Whiting et al., Rationale and Plan for Vitamin D Food Fortification: A Review and Guidance Paper, Front. Endocrinol,
doi:10.3389/fendo.2018.00373
Pittas, Dawson-Hughes, Sheehan, Ware, Knowler et al., Vitamin D Supplementation and Prevention of Type 2 Diabetes, N. Engl. J. Med,
doi:10.1056/NEJMoa1900906
Pludowski, Holick, Grant, Konstantynowicz, Mascarenhas et al., Vitamin D supplementation guidelines, J. Steroid Biochem. Mol. Biol,
doi:10.1016/j.jsbmb.2017.01.021
Poudel-Tandukar, Poudel, Jimba, Kobayashi, Johnson et al., Serum 25-hydroxyvitamin d levels and C-reactive protein in persons with human immunodeficiency virus infection, AIDS Res. Hum. Retrovir,
doi:10.1089/aid.2012.0120
Quraishi, Bittner, Blum, Hutter, Camargo et al., Association between preoperative 25-hydroxyvitamin D level and hospital-acquired infections following Roux-en-Y gastric bypass surgery, JAMA Surg,
doi:10.1001/jamasurg.2013.3176
Rejnmark, Bislev, Cashman, Eiriksdottir, Gaksch et al., Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data, PLoS ONE,
doi:10.1371/journal.pone.0180512
Rondanelli, 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:10.1155/2018/5813095
Ross, Manson, Abrams, Aloia, Brannon et al., The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2010-2704
Rossi, Fanous, Colin, Viral strategies predisposing to respiratory bacterial superinfections, Pediatr. Pulmonol,
doi:10.1002/ppul.24699
Sabetta, Depetrillo, Cipriani, Smardin, Burns et al., Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults, PLoS ONE
Schwalfenberg, A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency, Mol. Nutr. Food Res,
doi:10.1002/mnfr.201000174
Sharifi, Vahedi, Nedjat, Rafiei, Hosseinzadeh-Attar, Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: A randomized placebo-controlled trial, APMIS,
doi:10.1111/apm.12982
Shirvani, 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/s41598-019-53864-1
Slow, Epton, Storer, Thiessen, Lim et al., Effect of adjunctive single high-dose vitamin D3 on outcome of community-acquired pneumonia in hospitalised adults: The VIDCAPS randomised controlled trial, Sci. Rep
Smith, Jones, Han, Alvarez, Sloan et al., High-Dose Vitamin D3 Administration Is Associated With Increases in Hemoglobin Concentrations in Mechanically Ventilated Critically Ill Adults: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial, JPEN J. Parenter. Enter. Nutr,
doi:10.1177/0148607116678197
Song, Xu, Bao, Zhang, Yu et al., From SARS to MERS, Thrusting Coronaviruses into the Spotlight, Viruses,
doi:10.3390/v11010059
Theron, Huang, Chen, Liu, Lei, A probable role for IFN-gamma in the development of a lung immunopathology in SARS, Cytokine,
doi:10.1016/j.cyto.2005.07.007
Thickett, Moromizato, Litonjua, Amrein, Quraishi et al., Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: A retrospective cohort study, BMJ Open Respir. Res,
doi:10.1136/bmjresp-2014-000074
Urashima, Mezawa, Noya, Camargo, Jr, Effects of vitamin D supplements on influenza A illness during the 2009 H1N1 pandemic: A randomized controlled trial, Food Funct,
doi:10.1039/C4FO00371C
Urashima, Segawa, Okazaki, Kurihara, Wada et al., Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren, Am. J. Clin. Nutr,
doi:10.3945/ajcn.2009.29094
Uwitonze, Razzaque, Role of Magnesium in Vitamin D Activation and Function, J. Am. Osteopath Assoc,
doi:10.7556/jaoa.2018.037
Valcour, Blocki, Hawkins, Rao, Effects of age and serum 25-OH-vitamin D on serum parathyroid hormone levels, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2012-2276
Van Groningen, Opdenoordt, Van Sorge, Telting, Giesen et al., Cholecalciferol loading dose guideline for vitamin D-deficient adults, Eur. J. Endocrinol,
doi:10.1530/EJE-09-0932
Vasarhelyi, Satori, Olajos, Szabo, Beko, Low vitamin D levels among patients at Semmelweis University: Retrospective analysis during a one-year period, Orv. Hetil,
doi:10.1556/OH.2011.29187
Veugelers, Pham, Ekwaru, Optimal Vitamin D Supplementation Doses that Minimize the Risk for Both Low and High Serum 25-Hydroxyvitamin D Concentrations in the General Population, Nutrients,
doi:10.3390/nu7125527
Villamor, Villar, Lozano, Herrera, Herran, Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome, Epidemiol. Infect
Wang, 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.2020.1585
Wei, Christakos, Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D, Nutrients,
doi:10.3390/nu7105392
Wimalawansa, Global epidemic of coronavirus-COVID-19: What we can do to minimze risksl, Eur. J. Biomed. Pharm. Sci
Xie, Xia, Zhang, Wu, Lu et al., Prevalence of Vitamin D Inadequacy Among Chinese Postmenopausal Women: A Nationwide, Multicenter, Cross-Sectional Study, Front. Endocrinol,
doi:10.3389/fendo.2018.00782
Yin, Wunderink, Mers, SARS and other coronaviruses as causes of pneumonia, Respirology,
doi:10.1111/resp.13196
Youssef, Ranasinghe, Grant, Peiris, Vitamin D's potential to reduce the risk of hospital-acquired infections, Derm. Endocrinol,
doi:10.4161/derm.20789
Zhang, Gao, Tian, Zheng, Wang et al., Association of serum 25-hydroxyvitamin D3 with adipokines and inflammatory marker in persons with prediabetes mellitus, Clin. Chim. Acta,
doi:10.1016/j.cca.2017.02.022
Zhao, Ran, Jiang, Hu, Yu et al., Vitamin D Alleviates Rotavirus Infection through a Microrna-155-5p Mediated Regulation of the TBK1/IRF3 Signaling Pathway In Vivo and In Vitro, Int. J. Mol. Sci,
doi:10.3390/ijms20143562
Zhong, Zheng, Li, Poon, Xie et al., Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, Lancet,
doi:10.1016/S0140-6736(03)14630-2
Zhou, Du, Huang, Wang, Shi et al., Preventive Effects of Vitamin D on Seasonal Influenza A in Infants: A Multicenter, Randomized, Open, Controlled Clinical Trial, Pediatr. Infect. Dis. J,
doi:10.1097/INF.0000000000001890
Zhou, Luo, Qin, The association between vitamin D deficiency and community-acquired pneumonia: A meta-analysis of observational studies, Medicine,
doi:10.1097/MD.0000000000017252
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3
Zhu, Wang, Wang, Ji, The association between vitamin D and COPD risk, severity, and exacerbation: An updated systematic review and meta-analysis, Int. J. Chron. Obstruct. Pulmon. Dis,
doi:10.2147/COPD.S101382
Zhu, Zhang, Wang, Li, Yang et al., A Novel Coronavirus from Patients with Pneumonia in China, N. Engl. J. Med,
doi:10.1056/NEJMoa2001017
{ 'indexed': {'date-parts': [[2024, 5, 14]], 'date-time': '2024-05-14T18:41:44Z', 'timestamp': 1715712104293},
'reference-count': 157,
'publisher': 'MDPI AG',
'issue': '4',
'license': [ { 'start': { 'date-parts': [[2020, 4, 2]],
'date-time': '2020-04-02T00:00:00Z',
'timestamp': 1585785600000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'https://creativecommons.org/licenses/by/4.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'abstract': '<jats:p>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.</jats:p>',
'DOI': '10.3390/nu12040988',
'type': 'journal-article',
'created': {'date-parts': [[2020, 4, 2]], 'date-time': '2020-04-02T15:57:14Z', 'timestamp': 1585843034000},
'page': '988',
'source': 'Crossref',
'is-referenced-by-count': 1204,
'title': 'Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections '
'and Deaths',
'prefix': '10.3390',
'volume': '12',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-1439-3285',
'authenticated-orcid': False,
'given': 'William',
'family': 'Grant',
'sequence': 'first',
'affiliation': []},
{'given': 'Henry', 'family': 'Lahore', 'sequence': 'additional', 'affiliation': []},
{'given': 'Sharon', 'family': 'McDonnell', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-6172-2005',
'authenticated-orcid': False,
'given': 'Carole',
'family': 'Baggerly',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-5859-7231',
'authenticated-orcid': False,
'given': 'Christine',
'family': 'French',
'sequence': 'additional',
'affiliation': []},
{'given': 'Jennifer', 'family': 'Aliano', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-4909-0065',
'authenticated-orcid': False,
'given': 'Harjit',
'family': 'Bhattoa',
'sequence': 'additional',
'affiliation': []}],
'member': '1968',
'published-online': {'date-parts': [[2020, 4, 2]]},
'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2001017'},
{'key': 'ref2', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(03)14630-2'},
{'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa1306742'},
{'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/v11010059'},
{'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/resp.13196'},
{'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.7189/jogh.09.020421'},
{'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMra070553'},
{'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ecl.2017.07.001'},
{'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jcv.2010.12.006'},
{'key': 'ref10', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/j.1365-2265.2011.04261.x'},
{'key': 'ref11', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7064240'},
{'key': 'ref12', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7105392'},
{'key': 'ref13', 'doi-asserted-by': 'publisher', 'DOI': '10.1039/c6pp00355a'},
{'key': 'ref14', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.clinthera.2017.04.004'},
{'key': 'ref15', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/ijms19082419'},
{'key': 'ref16', 'doi-asserted-by': 'publisher', 'DOI': '10.1155/2018/5813095'},
{'key': 'ref17', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu12010236'},
{'key': 'ref18', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/mnfr.201000174'},
{'key': 'ref19', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/cei.13042'},
{'key': 'ref20', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268820000151'},
{'key': 'ref21', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/ppul.24699'},
{'key': 'ref22', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.1123933'},
{'key': 'ref23', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.0803736'},
{'key': 'ref24', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0029665111003351'},
{'key': 'ref25', 'doi-asserted-by': 'publisher', 'DOI': '10.1517/14712598.7.9.1449'},
{'key': 'ref26', 'doi-asserted-by': 'publisher', 'DOI': '10.5114/ceji.2015.51359'},
{'key': 'ref27', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0025333'},
{'key': 'ref28', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/ijms20143562'},
{'key': 'ref29', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s11010-019-03658-w'},
{'key': 'ref30', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30183-5'},
{'key': 'ref31', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/apm.12982'},
{'key': 'ref32', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0029665110001722'},
{ 'key': 'ref33',
'doi-asserted-by': 'crossref',
'first-page': '3032',
'DOI': '10.4049/jimmunol.134.5.3032',
'article-title': '1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte '
'activity in vitro',
'volume': '134',
'author': 'Lemire',
'year': '1985',
'journal-title': 'J. Immunol.'},
{'key': 'ref34', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7043011'},
{'key': 'ref35', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.0803217'},
{'key': 'ref36', 'doi-asserted-by': 'publisher', 'DOI': '10.1556/OH.2011.29187'},
{ 'key': 'ref37',
'doi-asserted-by': 'publisher',
'DOI': '10.3760/cma.j.issn.0254-6450.2020.02.003'},
{'key': 'ref38', 'doi-asserted-by': 'publisher', 'DOI': '10.1172/JCI112134'},
{'key': 'ref39', 'doi-asserted-by': 'publisher', 'DOI': '10.4161/derm.20731'},
{'key': 'ref40', 'doi-asserted-by': 'publisher', 'DOI': '10.1128/AAC.01226-17'},
{'key': 'ref41', 'doi-asserted-by': 'publisher', 'DOI': '10.1556/1886.2019.00016'},
{'key': 'ref42', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/14787210.2020.1706483'},
{ 'key': 'ref43',
'first-page': '432',
'article-title': 'Global epidemic of coronavirus--COVID-19: What we can do to minimze '
'risksl',
'volume': '7',
'author': 'Wimalawansa',
'year': '2020',
'journal-title': 'Eur. J. Biomed. Pharm. Sci.'},
{'key': 'ref44', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s13054-019-2539-x'},
{'key': 'ref45', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0022172400068728'},
{'key': 'ref46', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268806007175'},
{'key': 'ref47', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/1743-422X-5-29'},
{'key': 'ref48', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0118108'},
{'key': 'ref49', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.ppat.0030151'},
{'key': 'ref50', 'doi-asserted-by': 'publisher', 'DOI': '10.1073/pnas.0806852106'},
{ 'key': 'ref51',
'doi-asserted-by': 'publisher',
'DOI': '10.1371/annotation/35686514-b7a9-4f65-9663-7baefc0d63c0'},
{'key': 'ref52', 'doi-asserted-by': 'publisher', 'DOI': '10.3945/ajcn.2009.29094'},
{'key': 'ref53', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/INF.0000000000001890'},
{'key': 'ref54', 'doi-asserted-by': 'publisher', 'DOI': '10.1039/C4FO00371C'},
{'key': 'ref55', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ibd/izy346'},
{'key': 'ref56', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/irv.12615'},
{'key': 'ref57', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0011088'},
{'key': 'ref58', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.1585'},
{'key': 'ref59', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30566-3'},
{'key': 'ref60', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.envint.2020.105536'},
{'key': 'ref61', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.tiv.2018.07.016'},
{'key': 'ref62', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S2213-8587(17)30357-1'},
{'key': 'ref63', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0180512'},
{'key': 'ref64', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/nure.12090'},
{'key': 'ref65', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2017.08.009'},
{'key': 'ref66', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa1809944'},
{'key': 'ref67', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa1900906'},
{'key': 'ref68', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00391-017-1237-z'},
{'key': 'ref69', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/MD.0000000000017252'},
{'key': 'ref70', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0175517'},
{'key': 'ref71', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijtb.2018.05.018'},
{'key': 'ref72', 'doi-asserted-by': 'publisher', 'DOI': '10.1089/aid.2012.0120'},
{'key': 'ref73', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cca.2017.02.022'},
{'key': 'ref74', 'doi-asserted-by': 'publisher', 'DOI': '10.7754/Clin.Lab.2017.170919'},
{'key': 'ref75', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12879-020-4879-1'},
{'key': 'ref76', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmjresp-2014-000074'},
{'key': 'ref77', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thoraxjnl-2014-206680'},
{'key': 'ref78', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0007114519000795'},
{'key': 'ref79', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.maturitas.2019.11.005'},
{'key': 'ref80', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2015.06.013'},
{'key': 'ref81', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fendo.2018.00782'},
{'key': 'ref82', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/sj.ejcn.1600870'},
{'key': 'ref83', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fendo.2018.00373'},
{'key': 'ref84', 'doi-asserted-by': 'publisher', 'DOI': '10.12659/MSM.904755'},
{'key': 'ref85', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.maturitas.2017.02.016'},
{'key': 'ref86', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0174298'},
{'key': 'ref87', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12872-019-1236-7'},
{'key': 'ref88', 'doi-asserted-by': 'publisher', 'DOI': '10.2147/COPD.S101382'},
{'key': 'ref89', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.fct.2018.01.052'},
{'key': 'ref90', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41598-018-32162-2'},
{'key': 'ref91', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ctim.2020.102346'},
{'key': 'ref92', 'doi-asserted-by': 'publisher', 'DOI': '10.1530/EC-18-0184'},
{'key': 'ref93', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jcte.2016.04.004'},
{'key': 'ref94', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.diabres.2018.02.023'},
{'key': 'ref95', 'doi-asserted-by': 'publisher', 'DOI': '10.1089/jwh.2018.7397'},
{'key': 'ref96', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12931-014-0131-0'},
{'key': 'ref97', 'doi-asserted-by': 'publisher', 'DOI': '10.5588/ijtld.14.0696'},
{'key': 'ref98', 'doi-asserted-by': 'publisher', 'DOI': '10.7860/JCDR/2017/25522.10187'},
{'key': 'ref99', 'doi-asserted-by': 'publisher', 'DOI': '10.1210/jc.2012-2276'},
{'key': 'ref100', 'doi-asserted-by': 'publisher', 'DOI': '10.3109/00365511003797172'},
{'key': 'ref101', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.l5021'},
{'key': 'ref102', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/1753-6405.12347'},
{'key': 'ref103', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.archger.2015.09.002'},
{'key': 'ref104', 'doi-asserted-by': 'publisher', 'DOI': '10.26355/eurrev_201806_15276'},
{'key': 'ref105', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu11092065'},
{'key': 'ref106', 'doi-asserted-by': 'publisher', 'DOI': '10.4269/ajtmh.2009.81.180'},
{'key': 'ref107', 'doi-asserted-by': 'publisher', 'DOI': '10.1155/2016/1016840'},
{'key': 'ref108', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268817002059'},
{'key': 'ref109', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ijid.2019.04.032'},
{'key': 'ref110', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12876-019-1004-2'},
{'key': 'ref111', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.antiviral.2018.07.025'},
{'key': 'ref112', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2019.02291'},
{'key': 'ref113', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12985-017-0683-y'},
{'key': 'ref114', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0073659'},
{'key': 'ref115', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.gene.2018.08.017'},
{'key': 'ref116', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/ped.12809'},
{'key': 'ref117', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cyto.2005.07.007'},
{'key': 'ref118', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/j.1365-2249.2004.02415.x'},
{'key': 'ref119', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cyto.2018.01.025'},
{'key': 'ref120', 'doi-asserted-by': 'publisher', 'DOI': '10.2307/4580340'},
{'key': 'ref121', 'doi-asserted-by': 'publisher', 'DOI': '10.4161/derm.1.4.9063'},
{'key': 'ref122', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s13524-019-00789-z'},
{'key': 'ref123', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268807008308'},
{'key': 'ref124', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/archinternmed.2008.604'},
{'key': 'ref125', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ehb.2019.03.010'},
{'key': 'ref126', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s00484-018-1633-0'},
{'key': 'ref127', 'doi-asserted-by': 'publisher', 'DOI': '10.1021/acs.est.9b04295'},
{'key': 'ref128', 'doi-asserted-by': 'publisher', 'DOI': '10.1177/0148607116678197'},
{ 'key': 'ref129',
'first-page': '547',
'article-title': 'Update: Severe acute respiratory syndrome--Toronto, Canada, 2003',
'volume': '52',
'year': '2003',
'journal-title': 'MMWR Morb. Mortal. Wkly. Rep.'},
{'key': 'ref130', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s15010-016-0920-0'},
{'key': 'ref131', 'doi-asserted-by': 'publisher', 'DOI': '10.4161/derm.20789'},
{'key': 'ref132', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamasurg.2013.3176'},
{'key': 'ref133', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0230336'},
{'key': 'ref134', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.i6583'},
{'key': 'ref135', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ajcn/77.1.204'},
{'key': 'ref136', 'doi-asserted-by': 'publisher', 'DOI': '10.1530/EJE-09-0932'},
{'key': 'ref137', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/cncr.24749'},
{'key': 'ref138', 'doi-asserted-by': 'publisher', 'DOI': '10.21873/anticanres.13984'},
{'key': 'ref139', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0111265'},
{'key': 'ref140', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41598-019-53864-1'},
{'key': 'ref141', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2018.12.010'},
{'key': 'ref142', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ajcn/61.3.638S'},
{'key': 'ref143', 'doi-asserted-by': 'publisher', 'DOI': '10.1210/jcem-8-11-895'},
{'key': 'ref144', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ajcn/nqy378'},
{'key': 'ref145', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s12020-017-1290-9'},
{'key': 'ref146', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2017.2115'},
{'key': 'ref147', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41430-020-0558-y'},
{'key': 'ref148', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41430-020-0564-0'},
{'key': 'ref149', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.annepidem.2009.03.021'},
{'key': 'ref150', 'doi-asserted-by': 'publisher', 'DOI': '10.1210/jc.2010-2704'},
{'key': 'ref151', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/19381980.2016.1187349'},
{'key': 'ref152', 'doi-asserted-by': 'publisher', 'DOI': '10.1210/jc.2011-0385'},
{'key': 'ref153', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7125527'},
{'key': 'ref154', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jsbmb.2017.01.021'},
{'key': 'ref155', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu11102452'},
{'key': 'ref156', 'doi-asserted-by': 'publisher', 'DOI': '10.1542/peds.2011-3029'},
{'key': 'ref157', 'doi-asserted-by': 'publisher', 'DOI': '10.7556/jaoa.2018.037'}],
'container-title': 'Nutrients',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/12/4/988/pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 9, 29]],
'date-time': '2023-09-29T12:20:56Z',
'timestamp': 1695990056000},
'score': 1,
'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/12/4/988'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 4, 2]]},
'references-count': 157,
'journal-issue': {'issue': '4', 'published-online': {'date-parts': [[2020, 4]]}},
'alternative-id': ['nu12040988'],
'URL': 'http://dx.doi.org/10.3390/nu12040988',
'relation': { 'has-preprint': [ { 'id-type': 'doi',
'id': '10.20944/preprints202003.0235.v1',
'asserted-by': 'object'},
{ 'id-type': 'doi',
'id': '10.20944/preprints202003.0235.v2',
'asserted-by': 'object'}]},
'ISSN': ['2072-6643'],
'subject': [],
'container-title-short': 'Nutrients',
'published': {'date-parts': [[2020, 4, 2]]}}