Association of Vitamin D levels on the Clinical Outcomes of Patients Hospitalized for COVID-19 in a Tertiary Hospital

Margarita Katrina Amor Tan; Rebecca Lim Alba; Kingbherly Li

doi:10.15605/jafes.038.01.07

Authors

Margarita Katrina Amor Tan Chinese General Hospital and Medical Center, Philippines https://orcid.org/0000-0001-9789-7755
Rebecca Lim Alba Chinese General Hospital and Medical Center, Philippines
Kingbherly Li Chinese General Hospital and Medical Center, Philippines https://orcid.org/0000-0002-3723-7410

DOI:

https://doi.org/10.15605/jafes.038.01.07

Keywords:

Vitamin D, Vitamin D deficiency, COVID-19

Abstract

Objectives. This study aimed to compare the severity of COVID-19, inflammatory parameters and clinical outcomes among patients with normal and subnormal levels of Vitamin D.

Methodology. This is a retrospective cohort study of 135 patients admitted in a tertiary hospital for COVID-19. Patients were grouped according to their Vitamin D level. Primary outcome measure was the composite of all-cause mortality and morbidity. Other outcome measures determined were the comparison among the groups on the severity of COVID-19 infection, changes in inflammatory parameters, length of hospital stay and duration of respiratory support.

Results. There was a significant trend of higher ICU admission (p=0.024), mortality (p=0.006) and poor clinical outcome (p=0.009) among the Vitamin D deficient group. No significant difference was found for most of the inflammatory parameters, duration of hospital stay and respiratory support. Overall, patients with deficient, but not insufficient Vitamin D level had 6 times higher odds of composite poor outcome than those with normal Vitamin D (crude OR=5.18, p=0.003; adjusted OR=6.3, p=0.043).

Conclusion. The inverse relationship between Vitamin D level and poor composite outcome observed in our study suggests that low Vitamin D may be a risk factor for poor prognosis among patients admitted for COVID-19.

Downloads

Download data is not yet available.

Author Biographies

Margarita Katrina Amor Tan, Chinese General Hospital and Medical Center, Philippines

Section of Endocrinology, Diabetes and Metabolism

Rebecca Lim Alba, Chinese General Hospital and Medical Center, Philippines

Section of Endocrinology, Diabetes and Metabolism

Kingbherly Li, Chinese General Hospital and Medical Center, Philippines

Section of Infectious Diseases

References

Holick MF. The Vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18(2):153-65. https://pubmed.ncbi.nlm.nih.gov/28516265. https://doi.org/10.1007/s11154-017-9424-1.

Angeles-Agdeppa I, Perlas LA, Capanzana M. Vitamin D status of Filipino adults: Evidence from the 8th National Nutrition Survey 2013. Malays J Nutr. 2018; 24(3):395-406.

Sung CC, Liao MT, Lu KC, Wu CC. Role of Vitamin D in insulin resistance. J Biomed Biotechnol. 2012;2012:634195. https://pubmed.ncbi.nlm.nih.gov/22988423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440067. https://doi.org/10.1155/2012/634195.

Aranow C. Vitamin D and the immune system. J Investig Med. 2011;59(6):881-6. https://pubmed.ncbi.nlm.nih.gov/21527855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166406. https://doi.org/10.2310/JIM.0b013e31821b8755.

Jain A, Chaurasia R, Sengar NS, Singh M, Mahor S, Narain S. Analysis of Vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep. 2020;10(1):20191. https://pubmed.ncbi.nlm.nih.gov/33214648. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677378. https://doi.org/10.1038/s41598-020-77093-z.

Ali N. Role of Vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020;13(10):1373-80. https://pubmed.ncbi.nlm.nih.gov/32605780. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305922. https://doi.org/10.1016/j.jiph.2020.06.021.

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):988. https://pubmed.ncbi.nlm.nih.gov/32252338. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231123. https://doi.org/10.3390/nu12040988.

Peng MY, Liu WC, Zheng JQ, et al. Immunological aspects of SARS-CoV-2 infection and the putative beneficial role of Vitamin-D. Int J Mol Sci. 2021;22(10):5251. https://pubmed.ncbi.nlm.nih.gov/34065735. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155889. https://doi.org/10.3390/ijms22105251.

Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of Vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30. Erratum in: J Clin Endocrinol Metab. 2011;96(12):3908. https://pubmed.ncbi.nlm.nih.gov/21646368.

https://doi.org/10.1210/jc.2011-0385.

World Health Organization. Clinical management of COVID-19 Interim Guidance; 2020. https://apps.who.int/iris/handle/10665/332196.

Demir M, Demir F, Aygun H. Vitamin D deficiency is associated with COVID- 19 positivity and severity of the disease. J Med Virol. 2021;93(5):2992-9. https://pubmed.ncbi.nlm.nih.gov/33512007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013436. https://doi.org/10.1002/jmv.26832.

Greenland S, Pearce N. Statistical foundations for model-based adjustments. Annu Rev Public Health. 2015;36:89-108. https://pubmed.ncbi.nlm.nih.gov/25785886. https://doi.org/10.1146/annurev-publhealth-031914-122559.

Palomer X, González-Clemente JM, Blanco-Vaca F, Mauricio D. Role of Vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10(3):185-97. https://pubmed.ncbi.nlm.nih.gov/18269634. https://doi.org/10.1111/j.1463-1326.2007.00710.x.

Vranić L, Mikolašević I, Milić S. Vitamin D deficiency: Consequence or cause of obesity? Medicina (Kaunas). 2019;55(9):541. https://pubmed.ncbi.nlm.nih.gov/31466220. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780345. https://doi.org/10.3390/medicina55090541.

Agarwal M, Phan A, Willix R Jr, Barber M, Schwarz ER. Is Vitamin D deficiency associated with heart failure? A review of current evidence. J Cardiovasc Pharmacol Ther. 2011;16(3-4):354-63. https://pubmed.ncbi.nlm.nih.gov/21304056. https://doi.org/10.1177/1074248410390214.

Campi I, Gennari L, Merlotti D, et al. Vitamin D and COVID-19 severity and related mortality: A prospective study in Italy. BMC Infect Dis. 2021;21(1):566. https://pubmed.ncbi.nlm.nih.gov/34126960. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200788. https://doi.org/10.1186/s12879-021-06281-7.

Pereira M, Dantas Damascena A, Galvão 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):1308-16. https://pubmed.ncbi.nlm.nih.gov/33146028. https://doi.org/10.1080/10408398.2020.1841090.

Fatemi A, Ardehali SH, Eslamian G, Noormohammadi M, Malek S. Association of Vitamin D deficiency with COVID-19 severity and mortality in Iranian people: A prospective observational study. Acute Crit Care. 2021;36(4):300-7. https://pubmed.ncbi.nlm.nih.gov/35263825. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907463. https://doi.org/10.4266/acc.2021.00605.

Samprathi M, Jayashree M. Biomarkers in COVID-19: An Up-To-Date review. Front Pediatr. 2021;8:607647. https://pubmed.ncbi.nlm.nih.gov/33859967. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042162. https://doi.org/10.3389/fped.2020.607647.

Daneshkhah A, Agrawal V, Eshein A, Subramanian H, Roy HK, Backman V. 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):2141-58. https://pubmed.ncbi.nlm.nih.gov/32876941. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465887. https://doi.org/10.1007/s40520-020-01677-y

Yao Y, Cao J, Wang Q, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: A case control study. J Intensive Care. 2020;8:49. https://pubmed.ncbi.nlm.nih.gov/32665858. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348129. https://doi.org/10.1186/s40560-020-00466-z.

Teama MAEM, Abdelhakam DA, Elmohamadi MA, Badr FM. Vitamin D deficiency as a predictor of severity in patients with COVID-19 infection. Sci Prog. 2021;104(3):368504211036854. https://pubmed.ncbi.nlm.nih.gov/34347528. https://doi.org/10.1177/00368504211036854.

Sengupta T, Majumder R, Majumder S. Role of Vitamin D in treating COVID-19-associated coagulopathy: Problems and perspectives. Mol Cell Biochem. 2021;476(6):2421-7. https://pubmed.ncbi.nlm.nih.gov/33604809. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891480. https://doi.org/10.1007/s11010-021-04093-6.

Li Y, Hu Y, Yu J, Ma T. Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia. Lab Invest. 2020;100(6):794-800. https://pubmed.ncbi.nlm.nih.gov/32341519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184820. https://doi.org/10.1038/s41374-020-0431-6.

Driggin E, Madhavan MV, Gupta A. The role of Vitamin D in cardiovascular disease and COVID-19. Rev Endocr Metab Disord. 2022;23(2):293-7. https://pubmed.ncbi.nlm.nih.gov/35233703. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888268. https://doi.org/10.1007/s11154-021-09674-w.

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):1195-8. https://pubmed.ncbi.nlm.nih.gov/32377965. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202265. https://doi.org/10.1007/s40520-020-01570-8.

Reis BZ, Fernandes AL, Sales LP, et al. Influence of Vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: A multicenter prospective cohort study. Am J Clin Nutr. 2021;114(2):598-604. https://pubmed.ncbi.nlm.nih.gov/34020451. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194634. https://doi.org/10.1093/ajcn/nqab151.

Orchard L, Baldry M, Nasim-Mohi M, et al. Vitamin-D levels and intensive care unit outcomes of a cohort of critically ill COVID-19 patients. Clin Chem Lab Med. 2021;19;59(6):1155-63. https://pubmed.ncbi.nlm.nih.gov/33554566. https://doi.org/10.1515/cclm-2020-1567.

Pecina JL, Merry SP, Park JG, Thacher TD. Vitamin D status and severe COVID-19 disease outcomes in hospitalized patients. J Prim Care Community Health. 2021;12:21501327211041206. https://pubmed.ncbi.nlm.nih.gov/34452582. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404616. https://doi.org/10.1177/21501327211041206.

Infante M, Buoso A, Pieri M, et al. Low Vitamin D status at admission as a risk factor for poor survival in hospitalized patients with COVID-19: An Italian

retrospective study. J Am Nutr Assoc. 2022;41(3):250-65. https://pubmed.ncbi.nlm.nih.gov/33600292.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899172. https://doi.org/10.1080/07315724.2021.1877580.

Jolliffe DA, Holt H, Greenig M, et al. Effect of a test-and-treat approach to Vitamin D supplementation on risk of all cause acute respiratory tract infection and COVID-19: Phase 3 randomised controlled trial (CORONAVIT). BMJ. 2022;378:e071230. https://pubmed.ncbi.nlm.nih.gov/36215226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9449358. https://doi.org/10.1136/bmj-2022-071230.

Syquio MVA, Genuino RNF, Tolosa MTS. Should Vitamin D supplements be used as adjunct treatment for COVID-19? Philippine COVID-19 Living Clinical Practice Guidelines. February 20, 2021. https://www.psmid.org/wp-content/uploads/2021/05/ADJUNCT_Vitamin-D_FINAL.pdf.