Acknowledgement
Ram Bajpai is affiliated with the National Institute for Health and Care Research (NIHR) Applied Research Collaboration (ARC) West Midlands. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
References
- Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020;12(4):988. https://doi.org/10.3390/nu12040988
- Shah K, Saxena D, Mavalankar D. Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis. QJM 2021;114(3):175-181. https://doi.org/10.1093/qjmed/hcab009
- Ebadi M, Montano-Loza AJ. Perspective: improving vitamin D status in the management of COVID-19. Eur J Clin Nutr 2020;74(6):856-859. https://doi.org/10.1038/s41430-020-0661-0
- Wei R, Christakos S. Mechanisms underlying the regulation of innate and adaptive immunity by vitamin D. Nutrients 2015;7(10):8251-8560. https://doi.org/10.3390/nu7105392
- Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord 2017;18(2):153-165. https://doi.org/10.1007/s11154-017-9424-1
- Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol 2017;7:697. https://doi.org/10.3389/fimmu.2016.00697
- Infante M, Ricordi C, Sanchez J, Clare-Salzler MJ, Padilla N, Fuenmayor V, et al. Influence of vitamin D on islet autoimmunity and beta-cell function in type 1 diabetes. Nutrients 2019;11(9):2185. https://doi.org/10.3390/nu11092185
- Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, DawsonHughes B, et al. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr Rev 2019;40(4):1109-1151. https://doi.org/10.1210/er.2018-00126
- Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, et al. Epidemic influenza and vitamin D. Epidemiol Infect 2006;134(6):1129-1140. https://doi.org/10.1017/S0950268806007175
- Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the epidemiology of influenza. Virol J 2008;5:29. https://doi.org/10.1186/1743-422X-5-29
- Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med 2009;169(6):626-632. https://doi.org/10.1001/archinternmed.2008.604
- Gombart AF, Pierre A, Maggini S. A review of micronutrients and the immune system-working in harmony to reduce the risk of infection. Nutrients 2020;12(1):236. https://doi.org/10.3390/nu12010236
- Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem 2010;285(4):2227-2231. https://doi.org/10.1074/jbc.C109.071225
- Panagiotou G, Tee SA, Ihsan Y, Athar W, Marchitelli G, Kelly D, et al. Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity. Clin Endocrinol (Oxf) 2020;93(4):508-511. https://doi.org/10.1111/cen.14276
- Berry DJ, Hesketh K, Power C, Hypponen E. Vitamin D status has a linear association with seasonal infections and lung function in British adults. Br J Nutr 2011;106(9):1433-1440. https://doi.org/10.1017/S0007114511001991
- Kralj M, Jakovac H. Vitamin D and COVID-19 in an immunocompromised patient with multiple comorbidities-a case report. Clin Case Rep 2021;9(4):2269-2275. https://doi.org/10.1002/ccr3.4010
- Parveen R, Sehar N, Bajpai R, Agarwal NB. Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis. Diabetes Res Clin Pract 2020;166:108295. https://doi.org/10.1016/j.diabres.2020.108295
- Mishra P, Parveen R, Agarwal NB. Role of vitamin D in risk reduction of COVID-19: a narrative review. Ann Natl Acad Med Sci (India) 2021;57(1):36-40. https://doi.org/10.1055/s-0041-1724460
- Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of vitamin D deficiency and treatment with COVID-19 incidence. MedRxiv [Preprint]. 2020 [cited 2021 Sep 10]. Available from: https://doi.org/10.1101/2020.05.08.20095893.
- D'Avolio A, Avataneo V, Manca A, Cusato J, De Nicolo A, Lucchini R, et al. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients 2020;12(5):1359. https://doi.org/10.3390/nu12051359
- Hastie CE, Mackay DF, Ho F, Celis-Morales CA, Katikireddi SV, Niedzwiedz CL, et al. Vitamin D concentrations and COVID-19 infection in UK Biobank. Diabetes Metab Syndr 2020;14(4):561-565. https://doi.org/10.1016/j.dsx.2020.04.050
- Zhou YF, Luo BA, Qin LL. The association between vitamin D deficiency and community-acquired pneumonia: a meta-analysis of observational studies. Medicine (Baltimore) 2019;98(38):e17252. https://doi.org/10.1097/md.0000000000017252
- Cutolo M, Paolino S, Smith V. Evidences for a protective role of vitamin D in COVID-19. RMD Open 2020;6(3):e001454. https://doi.org/10.1136/rmdopen-2020-001454
- Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. The possible role of vitamin D in suppressing cytokine storm and associated mortality in COVID-19 patients. MedRxiv [Preprint]. 2020 [cited 2021 Oct 2]. Available from: https://doi.org/10.1101/2020.04.08.20058578.
- Darling AL, Ahmadi KR, Ward KA, Harvey NC, Alves AC, Dunn-Walters DK, et al. Vitamin D status, body mass index, ethnicity and COVID-19: initial analysis of the first-reported UK Biobank COVID-19 positive cases (n 580) compared with negative controls (n 723). MedRxiv [Preprint]. 2020 [cited 2021 Oct 2]. Available from: https://doi.org/10.1101/2020.04.29.20084277.
- De Smet DD, De Smet K, Herroelen P, Gryspeerdt S, Martens GA. Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics. MedRxiv [Preprint]. 2020 [cited 2021 Oct 2]. Available from: https://doi.org/10.1101/2020.05.01.20079376.
- Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res 2020;32(7):1195-1198. https://doi.org/10.1007/s40520-020-01570-8
- Lau FH, Majumder R, Torabi R, Saeg F, Hoffman R, Cirillo JD, et al. Vitamin D insufficiency is prevalent in severe COVID-19. MedRxiv [Preprint]. 2020 [cited 2021 Oct 2]. Available from: https://doi.org/10.1101/2020.04.24.20075838.
- Li Y, Li Q, Zhang N, Liu Z. Sunlight and vitamin D in the prevention of coronavirus disease (COVID-19) infection and mortality in the United States. Res Sq [Preprint]. 2020 [cited 2021 Oct 2]. Available from: https://doi.org/10.21203/rs.3.rs-32499/v1.
- Teshome A, Adane A, Girma B, Mekonnen ZA. The impact of vitamin D level on COVID-19 infection: systematic review and meta-analysis. Front Public Health 2021;9:624559. https://doi.org/10.3389/fpubh.2021.624559
- Crafa A, Cannarella R, Condorelli RA, Mongioi LM, Barbagallo F, Aversa A, et al. Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: a systematic review and meta-analysis. EClinicalMedicine 2021;37:100967. https://doi.org/10.1016/j.eclinm.2021.100967
- Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.
- Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283(15):2008-2012. https://doi.org/10.1001/jama.283.15.2008
- National Heart, Lung, and Blood Institute. Study quality assessment tools [cited 2020 Jun 9]. Available from: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.
- Abdollahi A, Kamali Sarvestani H, Rafat Z, Ghaderkhani S, Mahmoudi-Aliabadi M, Jafarzadeh B, et al. The association between the level of serum 25(OH) vitamin D, obesity, and underlying diseases with the risk of developing COVID-19 infection: a case-control study of hospitalized patients in Tehran, Iran. J Med Virol 2021;93(4):2359-2364. https://doi.org/10.1002/jmv.26726
- Alguwaihes AM, Sabico S, Hasanato R, Al-Sofiani ME, Megdad M, Albader SS, et al. Severe vitamin D deficiency is not related to SARS-CoV-2 infection but may increase mortality risk in hospitalized adults: a retrospective case-control study in an Arab Gulf country. Aging Clin Exp Res 2021;33(5):1415-1422. https://doi.org/10.1007/s40520-021-01831-0
- Al-Daghri NM, Amer OE, Alotaibi NH, Aldisi DA, Enani MA, Sheshah E, et al. Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study. J Transl Med 2021;19(1):166. https://doi.org/10.1186/s12967-021-02838-x
- Hernandez JL, Nan D, Fernandez-Ayala M, Garcia-Unzueta M, Hernandez-Hernandez MA, Lopez-Hoyos M, et al. Vitamin D status in hospitalized patients with SARS-CoV-2 infection. J Clin Endocrinol Metab 2021;106(3):e1343-e1353. https://doi.org/10.1210/clinem/dgaa733
- Ferrari D, Locatelli M, Faraldi M, Lombardi G. Changes in 25-(OH) vitamin D levels during the SARS-CoV-2 outbreak: lockdown-related effects and first-to-second wave difference-an observational study from northern Italy. Biology (Basel) 2021;10(3):237.
- Li Y, Tong CH, Bare LA, Devlin JJ. Assessment of the association of vitamin D level with SARS-CoV-2 seropositivity among working-age adults. JAMA Netw Open 2021;4(5):e2111634. https://doi.org/10.1001/jamanetworkopen.2021.11634
- Sulli A, Gotelli E, Casabella A, Paolino S, Pizzorni C, Alessandri E, et al. Vitamin D and lung outcomes in elderly COVID-19 patients. Nutrients 2021;13(3):717. https://doi.org/10.3390/nu13030717
- Al-Daghri NM, Al-Saleh Y, Aljohani N, Sulimani R, Al-Othman AM, Alfawaz H, et al. Vitamin D status correction in Saudi Arabia: an experts' consensus under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (ESCEO). Arch Osteoporos 2017;12(1):1. https://doi.org/10.1007/s11657-016-0295-y
- Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, 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 2019;180(4):P23-P54. https://doi.org/10.1530/EJE-18-0736
- Gaudio A, Murabito AR, Agodi A, Montineri A, Castellino P, D O CoV Research. Vitamin D levels are reduced at the time of hospital admission in Sicilian SARS-CoV-2-positive patients. Int J Environ Res Public Health 2021;18(7):3491. https://doi.org/10.3390/ijerph18073491
- Livingston M, Plant A, Dunmore S, Hartland A, Jones S, Laing I, et al. Detectable respiratory SARS-CoV-2 RNA is associated with low vitamin D levels and high social deprivation. Int J Clin Pract 2021;75(7):e14166.
- Merzon E, Tworowski D, Gorohovski A, Vinker S, Golan Cohen A, Green I, 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 2020;287(17):3693-3702. https://doi.org/10.1111/febs.15495
- Wirral Clinical Commissioning Group. Treatment of vitamin D deficiency in adults; 2020 [cited 2022 Jul 19]. Available from: https://mm.wirral.nhs.uk/document_uploads/guidelines/Vitamin%20D%20Guidelines%20for%20Adults%20v2.pdf.
- Higgins J, Green S. Cochrane handbook for systematic reviews of interventions; 2011 [cited 2022 Jul 19]. Available from: https://www.radioterapiaitalia.it/wp-content/uploads/2017/01/cochrane-handbook-for-systematic-reviews-of-interventions.pdf.
- Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56(2):455-463. https://doi.org/10.1111/j.0006-341X.2000.00455.x
- IntHout J, Ioannidis JP, Rovers MM, Goeman JJ. Plea for routinely presenting prediction intervals in meta-analysis. BMJ Open 2016;6(7):e010247. https://doi.org/10.1136/bmjopen-2015-010247
- Raisi-Estabragh Z, McCracken C, Bethell MS, Cooper J, Cooper C, Caulfield MJ, et al. Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank. J Public Health (Oxf) 2020;42(3):451-460. https://doi.org/10.1093/pubmed/fdaa095
- Raesi A, Saedi Dezaki E, Moosapour H, Saeidifard F, Habibi Z, Rahmani F, et al. Hypocalcemia in Covid-19: a prognostic marker for severe disease. Iran J Pathol 2021;16(2):144-153.
- Szarpak L, Rafique Z, Gasecka A, Chirico F, Gawel W, Hernik J, et al. A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J 2021;28(5):647-654. https://doi.org/10.5603/CJ.a2021.0072
- Bassatne A, Basbous M, Chakhtoura M, El Zein O, Rahme M, El-Hajj Fuleihan G. The link between COVID-19 and vItamin D (VIVID): a systematic review and meta-analysis. Metabolism 2021;119:154753. https://doi.org/10.1016/j.metabol.2021.154753
- Liu N, Sun J, Wang X, Zhang T, Zhao M, Li H. Low vitamin D status is associated with coronavirus disease 2019 outcomes: a systematic review and meta-analysis. Int J Infect Dis 2021;104:58-64. https://doi.org/10.1016/j.ijid.2020.12.077
- Pereira M, Dantas Damascena A, Galvao Azevedo LM, de Almeida Oliveira T, da Mota Santana J. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr 2022;62(5):1308-1316. https://doi.org/10.1080/10408398.2020.1841090
- Ghasemian R, Shamshirian A, Heydari K, Malekan M, AlizadehNavaei R, Ebrahimzadeh MA, et al. The role of vitamin D in the age of COVID-19: a systematic review and meta-analysis. Int J Clin Pract 2021;75(11):e14675.
- Munshi R, Hussein MH, Toraih EA, Elshazli RM, Jardak C, Sultana N, et al. Vitamin D insufficiency as a potential culprit in critical COVID-19 patients. J Med Virol 2021;93(2):733-740. https://doi.org/10.1002/jmv.26360
- Cai H. Sex difference and smoking predisposition in patients with COVID-19. Lancet Respir Med 2020;8(4):e20. https://doi.org/10.1016/s2213-2600(20)30117-x
- Wenham C, Smith J, Morgan R; Gender and COVID-19 Working Group. COVID-19: the gendered impacts of the outbreak. Lancet 2020;395(10227):846-848. https://doi.org/10.1016/s0140-6736(20)30526-2
- Muscogiuri G, Barrea L, Somma CD, Laudisio D, Salzano C, Pugliese G, et al. Sex differences of vitamin D status across BMI classes: an observational prospective cohort study. Nutrients 2019;11(12):3034. https://doi.org/10.3390/nu11123034
- Sanghera DK, Sapkota BR, Aston CE, Blackett PR. Vitamin D status, gender differences, and cardiometabolic health disparities. Ann Nutr Metab 2017;70(2):79-87. https://doi.org/10.1159/000458765
- Pagano MT, Peruzzu D, Ruggieri A, Ortona E, Gagliardi MC. Vitamin D and sex differences in COVID-19. Front Endocrinol (Lausanne) 2020;11:567824. https://doi.org/10.3389/fendo.2020.567824
- Ye K, Tang F, Liao X, Shaw BA, Deng M, Huang G, et al. Does serum vitamin D level affect COVID-19 infection and its severity?-A case-control study. J Am Coll Nutr 2021;40(8):724-731. https://doi.org/10.1080/07315724.2020.1826005
- Murdaca G, Pioggia G, Negrini S. Vitamin D and Covid-19: an update on evidence and potential therapeutic implications. Clin Mol Allergy 2020;18(1):23. https://doi.org/10.1186/s12948-020-00139-0
- Baktash V, Hosack T, Patel N, Shah S, Kandiah P, Van den Ab-beele K, et al. Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgrad Med J 2021;97(1149):442-447. https://doi.org/10.1136/postgradmedj-2020-138712
- Campi I, Gennari L, Merlotti D, Mingiano C, Frosali A, Giovanelli L, et al. Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy. BMC Infect Dis 2021;21(1):566. https://doi.org/10.1186/s12879-021-06281-7
- Kweder H, Eidi H. Vitamin D deficiency in elderly: risk factors and drugs impact on vitamin D status. Avicenna J Med 2018;8(4):139-146. https://doi.org/10.4103/ajm.AJM_20_18
- Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J 2020;55(5):2000547. https://doi.org/10.1183/13993003.00547-2020
- Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323(11):1061-1069. https://doi.org/10.1001/jama.2020.1585
- Ho JS, Fernando DI, Chan MY, Sia CH. Obesity in COVID-19: a systematic review and meta-analysis. Ann Acad Med Singap 2020;49(12):996-1008. https://doi.org/10.47102/annals-acadmedsg.2020299
- Mamelund SE, Shelley-Egan C, Rogeberg O. The association between socioeconomic status and pandemic influenza: systematic review and meta-analysis. PLoS One 2021;16(9):e0244346. https://doi.org/10.1371/journal.pone.0244346
- Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARSCoV-2: a systematic review and meta-analysis. Int J Infect Dis 2020;94:91-95. https://doi.org/10.1016/j.ijid.2020.03.017