open access

Vol 6, No 3 (2021)
Review paper
Published online: 2021-08-09
Get Citation

Relationship between serum 25-hydroxyvitamin D concentration and acute inflammatory markers in hospitalized patients with SARS-CoV-2 infection

Teodoro J. Oscanoa12, José Amado12, Rawia A. Ghashut3, Roman Romero-Ortuno45
·
Disaster Emerg Med J 2021;6(3):144-153.
Affiliations
  1. Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
  2. Faculty of Medicine, Universidad de San Martín de Porres, Drug Safety Research Centre, Hospital Almenara, ESSALUD, Lima, Peru
  3. Academic Unit of Anaesthesia, College of Medical, Veterinary and Life of Sciences, University of Glasgow, United Kingdom
  4. Discipline of Medical Gerontology, Mercer’s Institute for Successful Ageing, St James’s Hospital, Dublin, Ireland
  5. Global Brain Health Institute, Trinity College, Dublin, Ireland

open access

Vol 6, No 3 (2021)
ORIGINAL ARTICLES
Published online: 2021-08-09

Abstract

INTRODUCTION: There is experimental and clinical evidence that the serum concentration of 25-hydroxyvita­min D [25(OH)D)] may decrease in acute systemic inflammatory responses; in this context, low values may not necessarily indicate a pre-existing deficiency. This may also apply to low 25(OH)D levels found in the context of the systemic inflammatory response caused by SARS-CoV-2 infection. To conduct a systematic review of the relationship between serum 25(OH)D and the concentrations of C-re­active protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor a (TNF-a) in acutely hospitalized patients with SARS-CoV-2 infection.  

MATERIAL AND METHODS: We searched PubMed, EMBASE, Google Scholar and the Cochrane Database of Systematic Reviews for studies published between January 2020 and February 2021. In each study, the au­thors compared levels of inflammatory markers between patients reported as having low levels of 25(OH) D and those above the study cut-off.

RESULTS: 18 studies were included (n = 3482, mean age 63.5 ± 9.3 years, 56.9% men). The cut-off for the definition of low 25(OH)D varied across studies. In all studies, mean values for inflammatory markers were higher in the low 25(OH)D groups. These differences were statistically significant (p < 0.05) in 6/15 studies with CRP, 4/8 with IL-6 and 0/1 with TNF-a.  

CONCLUSIONS: Markers of acute systemic inflammatory response were elevated in patients with SARS-CoV-2 infection and low concentrations of 25(OH)D. Therefore, the vitamin D status in those patients should be interpreted with caution, and studies should be designed to assess whether hypovitaminosis D could be an epiphenomenon.

Abstract

INTRODUCTION: There is experimental and clinical evidence that the serum concentration of 25-hydroxyvita­min D [25(OH)D)] may decrease in acute systemic inflammatory responses; in this context, low values may not necessarily indicate a pre-existing deficiency. This may also apply to low 25(OH)D levels found in the context of the systemic inflammatory response caused by SARS-CoV-2 infection. To conduct a systematic review of the relationship between serum 25(OH)D and the concentrations of C-re­active protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor a (TNF-a) in acutely hospitalized patients with SARS-CoV-2 infection.  

MATERIAL AND METHODS: We searched PubMed, EMBASE, Google Scholar and the Cochrane Database of Systematic Reviews for studies published between January 2020 and February 2021. In each study, the au­thors compared levels of inflammatory markers between patients reported as having low levels of 25(OH) D and those above the study cut-off.

RESULTS: 18 studies were included (n = 3482, mean age 63.5 ± 9.3 years, 56.9% men). The cut-off for the definition of low 25(OH)D varied across studies. In all studies, mean values for inflammatory markers were higher in the low 25(OH)D groups. These differences were statistically significant (p < 0.05) in 6/15 studies with CRP, 4/8 with IL-6 and 0/1 with TNF-a.  

CONCLUSIONS: Markers of acute systemic inflammatory response were elevated in patients with SARS-CoV-2 infection and low concentrations of 25(OH)D. Therefore, the vitamin D status in those patients should be interpreted with caution, and studies should be designed to assess whether hypovitaminosis D could be an epiphenomenon.

Get Citation

Keywords

SARS-CoV-2, COVID-19, interleukin 6, C-reactive protein, vitamin D, 25-hydroxyvitamin D

About this article
Title

Relationship between serum 25-hydroxyvitamin D concentration and acute inflammatory markers in hospitalized patients with SARS-CoV-2 infection

Journal

Disaster and Emergency Medicine Journal

Issue

Vol 6, No 3 (2021)

Article type

Review paper

Pages

144-153

Published online

2021-08-09

Page views

6732

Article views/downloads

516

DOI

10.5603/DEMJ.a2021.0024

Bibliographic record

Disaster Emerg Med J 2021;6(3):144-153.

Keywords

SARS-CoV-2
COVID-19
interleukin 6
C-reactive protein
vitamin D
25-hydroxyvitamin D

Authors

Teodoro J. Oscanoa
José Amado
Rawia A. Ghashut
Roman Romero-Ortuno

References (50)
  1. Johns Hopkins University. The Grants Register 2021. 2020: 496–496.
  2. Pereira M, Dantas Damascena A, Galvão Azevedo LM, et al. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2020 [Epub ahead of print]: 1–9.
  3. Liu N, Sun J, Wang X, et al. 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.
  4. Munshi R, Hussein MH, Toraih EA, et al. Vitamin D insufficiency as a potential culprit in critical COVID-19 patients. J Med Virol. 2021; 93(2): 733–740.
  5. Kazemi A, Mohammadi V, Aghababaee SK, et al. Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis. Adv Nutr. 2021 [Epub ahead of print].
  6. Silva MC, Furlanetto TW. Does serum 25-hydroxyvitamin D decrease during acute-phase response? A systematic review. Nutr Res. 2015; 35(2): 91–96.
  7. Duncan A, Talwar D, McMillan DC, et al. Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements. Am J Clin Nutr. 2012; 95(1): 64–71.
  8. Ghashut RA, Talwar D, Kinsella J, et al. The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin. PLoS One. 2014; 9(3): e92614.
  9. Szeto B, Zucker JE, LaSota ED, et al. Vitamin D Status and COVID-19 Clinical Outcomes in Hospitalized Patients. Endocr Res. 2021; 46(2): 66–73.
  10. Shah K, Saxena D, Mavalankar D. Vitamin D supplementation, COVID-19 and disease severity: a meta-analysis. QJM. 2021; 114(3): 175–181.
  11. Smolders J, van den Ouweland J, Geven C, et al. Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism. 2021; 115: 154434.
  12. Moher D, Liberati A, Tetzlaff J, et al. PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Med. 2009; 3(3): e123–e130.
  13. Yadav A, Mohite S. A Review on Severe Acute Respiratory Infection (SARI) and its Clinical Management in Suspect/Confirmed Novel Coronavirus (nCoV) Cases. Research Journal of Pharmaceutical Dosage Forms and Technology. 2020; 12(3): 178.
  14. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25(9): 603–605.
  15. Higgins JPT, Altman DG, Gøtzsche PC, et al. Cochrane Bias Methods Group, Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928.
  16. Benskin LL. A Basic Review of the Preliminary Evidence That COVID-19 Risk and Severity Is Increased in Vitamin D Deficiency. Front Public Health. 2020; 8: 513.
  17. World Medical Association (WMA). International Year Book and Statesmen's Who's Who. .
  18. Buchtele N, Lobmeyr E, Cserna J, et al. Prevalence and Impact of Vitamin D Deficiency in Critically Ill Cancer Patients Admitted to the Intensive Care Unit. Nutrients. 2020; 13(1).
  19. Radujkovic A, Hippchen T, Tiwari-Heckler S, et al. Vitamin D Deficiency and Outcome of COVID-19 Patients. Nutrients. 2020; 12(9).
  20. Luo X, Liao Q, Shen Y, et al. Vitamin D Deficiency Is Associated with COVID-19 Incidence and Disease Severity in Chinese People [corrected]. J Nutr. 2021; 151(1): 98–103.
  21. Vassiliou AG, Jahaj E, Pratikaki M, et al. Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort. Nutrients. 2020; 12(12).
  22. Jain A, Chaurasia R, Sengar NS, et al. 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.
  23. Jevalikar G, Mithal A, Singh A, et al. Lack of Association of Baseline 25-Hydroxyvitamin D Levels and Cholecalciferol Treatment With Disease Severity and Mortality in Indian Patients Hospitalized for Covid-19. .
  24. Tehrani S, Khabiri N, Moradi H, et al. Evaluation of vitamin D levels in COVID-19 patients referred to Labafinejad hospital in Tehran and its relationship with disease severity and mortality. Clin Nutr ESPEN. 2021; 42: 313–317.
  25. Carpagnano GE, Di Lecce V, Quaranta VN, et al. Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest. 2021; 44(4): 765–771.
  26. Cereda E, Bogliolo L, Klersy C, et al. NUTRI-COVID19 IRCCS San Matteo Pavia Collaborative Group. Vitamin D 25OH deficiency in COVID-19 patients admitted to a tertiary referral hospital. Clin Nutr. 2021; 40(4): 2469–2472.
  27. Ricci A, Pagliuca A, D'Ascanio M, et al. Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients. Respir Res. 2021; 22(1): 76.
  28. 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.
  29. 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): 2992–2999.
  30. Karahan S, Katkat F. Impact of Serum 25(OH) Vitamin D Level on Mortality in Patients with COVID-19 in Turkey. J Nutr Health Aging. 2021; 25(2): 189–196.
  31. Tuncay ME, Gemcioglu E, Kayaaslan B, et al. A notable key for estimating the severity of COVID-19: 25-hydroxyvitamin D status. Turkish Journal of Biochemistry. 2021; 46(2): 167–172.
  32. Panagiotou G, Tee SuA, Ihsan Y, 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.
  33. 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.
  34. 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; 59(6): 1155–1163.
  35. Mazziotti G, Lavezzi E, Brunetti A, et al. Humanitas COVID19 Task Force. Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19. J Endocrinol Invest. 2021 [Epub ahead of print].
  36. Clements DN, Bruce G, Ryan JM, et al. Effects of surgery on free and total 25 hydroxyvitamin D concentrations in dogs. J Vet Intern Med. 2020; 34(6): 2617–2621.
  37. Waldron JL, Ashby HL, Cornes MP, et al. Vitamin D: a negative acute phase reactant. J Clin Pathol. 2013; 66(7): 620–622.
  38. Reid D, Toole BJ, Knox S, et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr. 2011; 93(5): 1006–1011.
  39. Louw JA, Werbeck A, Louw ME, et al. Blood vitamin concentrations during the acute-phase response. Crit Care Med. 1992; 20(7): 934–941.
  40. Barth JH, Field HP, Mather AN, et al. Serum 25 hydroxy-vitamin D does not exhibit an acute phase reaction after acute myocardial infarction. Ann Clin Biochem. 2012; 49(Pt 4): 399–401.
  41. Bang UC, Novovic S, Andersen AM, et al. Variations in serum 25-hydroxyvitamin D during acute pancreatitis: an exploratory longitudinal study. Endocr Res. 2011; 36(4): 135–141.
  42. Bertoldo F, Pancheri S, Zenari S, et al. Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion. J Bone Miner Res. 2010; 25(3): 447–454.
  43. Krishnan A, Ochola J, Mundy J, et al. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care. 2010; 14(6): R216.
  44. Quraishi SA, Camargo CA. Vitamin D in acute stress and critical illness. Curr Opin Clin Nutr Metab Care. 2012; 15(6): 625–634.
  45. McMillan DC, Maguire D, Talwar D. Relationship between nutritional status and the systemic inflammatory response: micronutrients. Proc Nutr Soc. 2019; 78(1): 56–67.
  46. Zgaga L, Laird E, Healy M. 25-Hydroxyvitamin D Measurement in Human Hair: Results from a Proof-of-Concept study. Nutrients. 2019; 11(2).
  47. MacDonell SO, Miller JC, Harper MJ, et al. A comparison of methods for adjusting biomarkers of iron, zinc, and selenium status for the effect of inflammation in an older population: a case for interleukin 6. Am J Clin Nutr. 2018; 107(6): 932–940.
  48. Celikbilek A. Vitamin D axis status and the severity of COVID-19. J Med Virol. 2021; 93(7): 4085.
  49. Powe CE, Evans MK, Wenger J, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013; 369(21): 1991–2000.
  50. Butler-Laporte G, Nakanishi T, Mooser V, et al. Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study. PLoS Med. 2021; 18(6): e1003605.

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 VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl