Journal of Preventive Medicine and Public Health

  • 제55권4호
  • /
  • Pages.321-333
  • /
  • 2022
  • /
  • 1975-8375(pISSN)
  • /
  • 2233-4521(eISSN)
대한예방의학회 (The Korean Society for Preventive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Vitamin D Deficiency and Comorbidities as Risk Factors of COVID-19 Infection: A Systematic Review and Meta-analysis

  • Mishra, Pinki (Centre for Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard) ;
  • Parveen, Rizwana (Centre for Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard) ;
  • Bajpai, Ram (School of Medicine, Keele University) ;
  • Agarwal, Nidhi (Centre for Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard)
  • 투고 : 2021.12.18
  • 심사 : 2022.05.09
  • 발행 : 2022.07.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objectives: Extensive evidence links low vitamin D status and comorbidities with coronavirus disease 2019 (COVID-19) outcomes, but the results of published studies are contradictory. Therefore, we investigated the association of lower levels of vitamin D and comorbidities with the risk of COVID-19 infection. Methods: We searched MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for articles published until August 20, 2021. Sixteen eligible studies were identified (386 631 patients, of whom 181 114 were male). We included observational cohort and case-control studies that evaluated serum levels of vitamin D in COVID-19-positive and COVID-19-negative patients. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results: Significantly lower vitamin D levels were found in COVID-19-positive patients (MD, -1.70; 95% CI, -2.74 to -0.66; p=0.001), but with variation by study design (case-control: -4.04; 95% CI, -5.98 to -2.10; p<0.001; cohort: -0.39; 95% CI, -1.62 to 0.84; p=0.538). This relationship was more prominent in female patients (MD, -2.18; 95% CI, -4.08 to -0.28; p=0.024) than in male patients (MD, -1.74; 95% CI, -3.79 to 0.31; p=0.096). Male patients showed higher odds of having low vitamin D levels (odds ratio [OR], 2.09; 95% CI, 1.38 to 3.17; p<0.001) than female patients (OR, 1.17; 95% CI, 0.74 to 1.86; p=0.477). Comorbidities showed inconsistent, but generally nonsignificant, associations with COVID-19 infection. Conclusions: Low serum vitamin-D levels were significantly associated with the risk of COVID-19 infection. This relationship was stronger in female than in male COVID-19 patients. Limited evidence was found for the relationships between comorbidities and COVID-19 infection, warranting large population-based studies to clarify these associations.

키워드

과제정보

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.

참고문헌

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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.
  20. 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
  21. 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
  22. 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
  23. 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
  24. 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.
  25. 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.
  26. 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.
  27. 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
  28. 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.
  29. 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.
  30. 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
  31. 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
  32. 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.
  33. 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
  34. 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.
  35. 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
  36. 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
  37. 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
  38. 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
  39. 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.
  40. 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
  41. 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
  42. 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
  43. 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
  44. 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
  45. 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.
  46. 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
  47. 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.
  48. 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.
  49. 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
  50. 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
  51. 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
  52. 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.
  53. 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
  54. 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
  55. 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
  56. 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
  57. 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.
  58. 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
  59. 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
  60. 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
  61. 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
  62. 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
  63. 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
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. 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
  70. 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
  71. 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
  72. 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
  73. 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