open access

Vol 28, No 5 (2021)
Original Article
Published online: 2021-07-02
Get Citation

A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19

Luiza Szarpak1, Zubaid Rafique2, Aleksandra Gasecka34, Francesco Chirico56, Wladyslaw Gawel78, Jacek Hernik9, Halla Kaminska810, Krzysztof J. Filipiak3, Milosz J. Jaguszewski11, Lukasz Szarpak912
DOI: 10.5603/CJ.a2021.0072
·
Pubmed: 34308537
·
Cardiol J 2021;28(5):647-654.
Affiliations
  1. Institute of Outcomes R esearch, Polonia University, Czestochowa, Poland
  2. Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, United States
  3. 1st Chair and Department of Cardiology, Medical University of Warsaw, Poland
  4. Department of Cardiology, University Medical Center Utrecht, The Netherlands
  5. Post-graduate School of Occupational Health, Università Cattolica del Sacro Cuore, Rome, Italy
  6. Health Service Department, Italian State Police, Ministry of the Interior, Milano, Italy
  7. Department of Surgery, The Silesian Hospital in Opava, Czech Republic
  8. Polish Society of Disaster Medicine, Warsaw, Poland
  9. Maria Sklodowska-Curie Medical Academy, Warsaw, Poland
  10. Department of Pediatrics and Children’s Diabetology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Zabrze, Poland
  11. 1st Department of Cardiology, Medical University of Gdansk, Poland
  12. Maria Sklodowska-Curie Bialystok Oncology Center, Bialystok, Poland

open access

Vol 28, No 5 (2021)
Original articles — COVID-19
Published online: 2021-07-02

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a disease primarily affecting the respiratory tract, however due to the nature of the pathogenesis it is able to affect the whole body. So far, no causative treatment has been found and the main strategy when dealing with COVID-19 relies on widespread vaccination programs and symptomatic treatment. Vitamin D due to its ability to modulate the immunological system has been proposed as a factor playing role in the organism response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we decided to perform this meta-analysis which aimed to establish a connection between vitamin D status and COVID-19 infection.
Methods: Study was designed as a systematic review and meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Collaboration Databases and Scopus electronic databases were searched for relevant studies from database inception to May 10th, 2021. Mean differences (MDs) with their 95% confidence intervals (CI) were calculated.
Results: Thirteen studies providing data for 14,485 participants met the inclusion criteria. Mean vitamin D levels in SARS-CoV-2 negative patients was 17.7 ± 6.9 ng/mL compared to SARS-CoV-2 positive patients 14.1 ± 8.2 ng/mL (MD = 3.93; 95% CI 2.84–5.02; I2 = 99%; p < 0.001).
Conclusions: Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a disease primarily affecting the respiratory tract, however due to the nature of the pathogenesis it is able to affect the whole body. So far, no causative treatment has been found and the main strategy when dealing with COVID-19 relies on widespread vaccination programs and symptomatic treatment. Vitamin D due to its ability to modulate the immunological system has been proposed as a factor playing role in the organism response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we decided to perform this meta-analysis which aimed to establish a connection between vitamin D status and COVID-19 infection.
Methods: Study was designed as a systematic review and meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Collaboration Databases and Scopus electronic databases were searched for relevant studies from database inception to May 10th, 2021. Mean differences (MDs) with their 95% confidence intervals (CI) were calculated.
Results: Thirteen studies providing data for 14,485 participants met the inclusion criteria. Mean vitamin D levels in SARS-CoV-2 negative patients was 17.7 ± 6.9 ng/mL compared to SARS-CoV-2 positive patients 14.1 ± 8.2 ng/mL (MD = 3.93; 95% CI 2.84–5.02; I2 = 99%; p < 0.001).
Conclusions: Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated.

Get Citation

Keywords

vitamin D, COVID-19, coronavirus disease 2019, SARS-CoV-2, systematic review, meta-analysis

About this article
Title

A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19

Journal

Cardiology Journal

Issue

Vol 28, No 5 (2021)

Article type

Original Article

Pages

647-654

Published online

2021-07-02

DOI

10.5603/CJ.a2021.0072

Pubmed

34308537

Bibliographic record

Cardiol J 2021;28(5):647-654.

Keywords

vitamin D
COVID-19
coronavirus disease 2019
SARS-CoV-2
systematic review
meta-analysis

Authors

Luiza Szarpak
Zubaid Rafique
Aleksandra Gasecka
Francesco Chirico
Wladyslaw Gawel
Jacek Hernik
Halla Kaminska
Krzysztof J. Filipiak
Milosz J. Jaguszewski
Lukasz Szarpak

References (52)
  1. Song F, Shi N, Shan F, et al. Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology. 2020; 295(1): 210–217. Erratum in: Radiology. 2020 Dec;297(3):E346..
  2. Dzieciatkowski T, Szarpak L, Filipiak KJ, et al. COVID-19 challenge for modern medicine. Cardiol J. 2020; 27(2): 175–183.
  3. Di Fusco M, Shea KM, Lin J, et al. Health outcomes and economic burden of hospitalized COVID-19 patients in the United States. J Med Econ. 2021; 24(1): 308–317.
  4. Hamming I, Timens W, Bulthuis MLC, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203(2): 631–637.
  5. Sungnak W, Huang Ni, Bécavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020; 26(5): 681–687.
  6. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery. 2020; 6(1).
  7. Sahraei Z, Shabani M, Shokouhi S, et al. Aminoquinolines against coronavirus disease 2019 (COVID-19): chloroquine or hydroxychloroquine. Int J Antimicrob Agents. 2020; 55(4): 105945.
  8. Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect. 2020; 53(3): 368–370.
  9. Szarpak Ł, Dzieciątkowski T, Jaguszewski MJ, et al. Is remdesivir important in clinical practice as a treatment of COVID-19? A study based on meta-analysis data. Pol Arch Intern Med. 2021; 131(1): 96–97.
  10. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020; 383(27): 2603–2615.
  11. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021; 384(5): 403–416.
  12. Ho JSY, Fernando DI, Chan MY, et al. Obesity in COVID-19: a systematic review and meta-analysis. Ann Acad Med Singap. 2020; 49(12): 996–1008.
  13. Abdi A, Jalilian M, Sarbarzeh PA, et al. Diabetes and COVID-19: a systematic review on the current evidences. Diabetes Res Clin Pract. 2020; 166: 108347.
  14. Hu L, Chen S, Fu Y, et al. Risk factors associated with clinical outcomes in 323 coronavirus disease 2019 (COVID-19) hospitalized patients in Wuhan, China. Clin Infect Dis. 2020; 71(16): 2089–2098.
  15. Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014; 144 Pt A: 138–145.
  16. Wacker M, Holick MF. Vitamin D: effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013; 5(1): 111–148.
  17. Hewison M, Freeman L, Hughes SV, et al. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol. 2003; 170(11): 5382–5390.
  18. Xu H, Soruri A, Gieseler RK, et al. 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes. Scand J Immunol. 1993; 38(6): 535–540.
  19. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine. 2009; 6(7): e1000097.
  20. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016; 355: i4919.
  21. McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. 2021; 12(1): 55–61.
  22. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005; 5: 13.
  23. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557–560.
  24. Abdollahi A, Kamali Sarvestani H, Rafat Z, 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.
  25. Alguwaihes A, Sabico S, Hasanato R, 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.
  26. Al-Daghri NM, Amer OE, Alotaibi NH, 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.
  27. Baktash V, Hosack T, Patel N, et al. Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgrad Med J. 2021; 97(1149): 442–447.
  28. D'Avolio A, Avataneo V, Manca A, et al. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients. 2020; 12(5).
  29. Hernández JL, Nan D, Fernandez-Ayala M, et al. Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection. J Clin Endocrinol Metab. 2021; 106(3): e1343–e1353.
  30. Im JH, Je YS, Baek J, et al. Nutritional status of patients with COVID-19. Int J Infect Dis. 2020; 100: 390–393.
  31. Livingston M, Plant A, Dunmore S, et al. Detectable respiratory SARS-CoV-2 RNA is associated with low vitamin D levels and high social deprivation. Int J Clin Pract. 2021 [Epub ahead of print]: e14166.
  32. Mardani R, Alamdary A, Mousavi Nasab SD, et al. Association of vitamin D with the modulation of the disease severity in COVID-19. Virus Res. 2020; 289: 198148.
  33. Merzon E, Tworowski D, Gorohovski A, 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.
  34. Raisi-Estabragh Z, McCracken C, Bethell MS, 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.
  35. Sulli A, Gotelli E, Casabella A, et al. Vitamin d and lung outcomes in elderly COVID-19 patients. Nutrients. 2021; 13(3).
  36. Ye K, Tang F, Liao X, et al. Does serum vitamin D level affect COVID-19 infection and its severity?-a case-control study. J Am Coll Nutr. 2020 [Epub ahead of print]: 1–8.
  37. Mitchell F. Vitamin-D and COVID-19: do deficient risk a poorer outcome? . Lancet Diabetes Endocrinol. 2020; 8(7): 570.
  38. Mok C, Ng Y, Ahidjo B, et al. Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis. bioRxiv. 2020.
  39. Martineau AR, Forouhi NG. Vitamin D for COVID-19: a case to answer? Lancet Diabetes Endocrinol. 2020; 8(9): 735–736.
  40. Petrakis D, Margină D, Tsarouhas K, et al. Obesity: a risk factor for increased COVID‑19 prevalence, severity and lethality (review). Mol Med Rep. 2020; 22(1): 9–19.
  41. Vranić L, Mikolašević I, Milić S. Vitamin D deficiency: consequence or cause of obesity? Medicina (Kaunas). 2019; 55(9).
  42. 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.
  43. Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020; 12(4).
  44. Bacon CJ, Gamble GD, Horne AM, et al. High-dose oral vitamin D3 supplementation in the elderly. Osteoporos Int. 2009; 20(8): 1407–1415.
  45. Bergman P. The link between vitamin D and COVID-19: distinguishing facts from fiction. J Intern Med. 2021; 289(1): 131–133.
  46. Daneshkhah A, Agrawal V, Eshein A, et al. Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients. Aging Clin Exp Res. 2020; 32(10): 2141–2158.
  47. Mehta S. Nutritional status and COVID-19: an opportunity for lasting change? Clin Med (Lond). 2020 [Epub ahead of print]; 20(3): 270–273.
  48. Martins EC, Silveira Ld, Viegas K, et al. Neutrophil-lymphocyte ratio in the early diagnosis of sepsis in an intensive care unit: a case-control study. Rev Bras Ter Intensiva. 2019; 31(1): 64–70.
  49. Wang Y, Ju M, Chen C, et al. Neutrophil-to-lymphocyte ratio as a prognostic marker in acute respiratory distress syndrome patients: a retrospective study. J Thorac Dis. 2018; 10(1): 273–282.
  50. VoPham T, Weaver MD, Hart JE, et al. Effect of social distancing on COVID-19 incidence and mortality in the US. medRxiv. 2020.
  51. Charlton J, Rudisill C, Bhattarai N, et al. Impact of deprivation on occurrence, outcomes and health care costs of people with multiple morbidity. J Health Serv Res Policy. 2013; 18(4): 215–223.
  52. Haugen J, Chandyo RK, Ulak M, et al. 25-Hydroxy-Vitamin D Concentration Is Not Affected by Severe or Non-Severe Pneumonia, or Inflammation, in Young Children. Nutrients. 2017; 9(1).

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl