The association between vitamin D levels and the clinical severity and inflammation markers in pediatric COVID-19 patients: single-center experience from a pandemic hospital
Elvan Bayramoğlu, Gülşen Akkoç, Ayşe Ağbaş, Özlem Akgün, Kamer Yurdakul, Hatice Nilgün Selçuk Duru, Murat Elevli
European Journal of Pediatrics, doi:10.1007/s00431-021-04030-1
Vitamin D has an immunomodulating property that regulates the inflammatory response. In this study, the aim was to evaluate the relationship between vitamin D levels and clinical severity and inflammation markers in children and adolescents with COVID-19. The clinical and laboratory records of 103 pediatric cases with COVID-19, whose vitamin D levels had been measured, were retrospectively reviewed. The cases were divided into groups according to their clinical severity (asymptomatic, mild, and moderate-to-severe) and vitamin D levels. The moderate-to-severe clinical group had significantly higher inflammation markers (CRP, procalcitonin, fibrinogen, D- dimer) and a lower lymphocyte count compared to both the mild and asymptomatic groups. The 25 OH vitamin D levels were also significantly lower (p < 0.001), and the ratio of vitamin D deficiency was 70.6% in the moderate-to-severe group. The vitamin D-deficient group had a significantly higher age and fibrinogen levels while also having a lower lymphocyte count compared to the insufficient and normal groups. The 25 OH vitamin D level was correlated positively with the lymphocyte count (r = 0.375, p = <0.001), and negatively with age (r = −0.496, p = <0.001), CRP (r = −0.309, p = 0.002) and fibrinogen levels (r = −0.381, p = <0.001). In a logistic regression analysis, vitamin D deficiency, D-dimer, and fibrinogen levels on admission were independent predictors of severe clinical course. Conclusion: This study revealed an association between vitamin D deficiency and clinical severity, in addition to inflammation markers in pediatric COVID-19 cases. Prophylactic vitamin D supplementation may be considered, especially in the adolescent age group.
Authors' contributions EB, GA, and AA design the study. EB, GA, KD, and OA data acquisition. EB and AA performed the statistical analysis. EB, AA, and GA wrote the manuscript. EB, GA, AA, HNSD, and ME reviewed the manuscript.
Conflict of interest The authors declare no competing interests. Ethics approval This study was approved by the local ethical committee (Haseki Training and Research Hospital, 2020-56, 14.05.2020).
Consent to participate None (retrospective study) Consent for publication All authors consent to the publication of the manuscript in European Journal of Pediatrics, should the article be accepted by the Editor-in-chief upon completion of the refereeing process.
References
Alipio, Vitamin D supplementation could possibly improve clinical outcomes of patients infected with coronavirus
Chen, Sims, Chen, Gu, Chen et al., Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation, J Immunol
Cui, Xu, Li, Qiao, Han et al., Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: role of reninangiotensin system, Redox Biol,
doi:10.1016/j.redox.2019.101295
Dancer, Parekh, Lax, Souza, Zheng et al., None
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res,
doi:10.1007/s40520-020-01570-8
Khare, Godbole, Pawar, Mohan, Pandey et al., None, Calcitriol
Kong, Zhu, Shi, Liu, Chen et al., VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system, Mol Endocrinol,
doi:10.1210/me.2013-1146
Lanza, Perez, Costa, Cordeiro, Palmeira et al., Covid-19: the renin-angiotensin system imbalance hypothesis, Clin Sci (Lond),
doi:10.1042/cs20200492
Lei, Zhang, Cheng, Lee, Mechanisms of action of vitamin D as supplemental therapy for pneumocystis pneumonia, Antimicrob Agents Chemother,
doi:10.1128/aac.01226-17
Lips, Cashman, Lamberg-Allardt, Bischoff-Ferrari, Obermayer-Pietsch 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,
doi:10.1530/EJE-18-0736
Liu, Li, Liu, Liang, Wang et al., Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients, EBioMedicine,
doi:10.1016/j.ebiom.2020.102763
Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science,
doi:10.1126/science.1123933
Lu, Stratton, Tang, Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle, J Med Virol,
doi:10.1002/jmv.25678
Luo, Zhou, Yan, Guo, Wang et al., Prognostic value of Creactive protein in patients with COVID-19, Clin Infect Dis,
doi:10.1093/cid/ciaa641
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, Bmj,
doi:10.1136/bmj.i6583
Munns, Shaw, Kiely, Specker, Thacher et al., Global consensus recommendations on prevention and management of nutritional rickets, J Clin Endocrinol Metab,
doi:10.1210/jc.2015-2175
Panarese, Shahini, Letter: Covid-19, and vitamin D, Alimentary Pharmacology & Therapeutics
Panfili, Roversi, Argenio, Rossi, Cappa et al., Possible role of vitamin D in Covid-19 infection in pediatric population, J Endocrinol Investig,
doi:10.1007/s40618-020-01327-0
Raharusun, Patterns of COVID-19 mortality and vitamin D: an Indonesian study
Sharifi, Vahedi, Nedjat, Rafiei, Hosseinzadeh-Attar, Effect of single-dose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebocontrolled trial, Apmis,
doi:10.1111/apm.12982
She, Liu, Liu, COVID-19 epidemic: disease characteristics in children, J Med Virol,
doi:10.1002/jmv.25807
Wan, Shang, Graham, Baric, Li, Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus, J Virol,
doi:10.1128/jvi.00127-20
Wang, Hu, Hu, Zhu, Liu et al., Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, Jama,
doi:10.1001/jama.2020.1585
Zhang, Leung, Richers, Liu, Remigio et al., Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1, J Immunol,
doi:10.4049/jimmunol.1102412
Zheng, Gao, Wang, Song, Liu et al., Functional exhaustion of antiviral lymphocytes in COVID-19 patients, Cell Mol Immunol,
doi:10.1038/s41423-020-0402-2
Zisi, Challa, Makis, The association between vitamin D status and infectious diseases of the respiratory system in infancy and childhood, Hormones (Athens),
doi:10.1007/s42000-019-00155-z
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'in Wuhan, China. Jama 323(11):1061–1069. '
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'unstructured': 'Cantorna MT (2010) Mechanisms underlying the effect of vitamin D on the '
'immune system. Proc Nutr Soc 69(3):286–289. '
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'year': '2017',
'unstructured': 'Lei GS, Zhang C, Cheng BH, Lee CH (2017) Mechanisms of action of vitamin '
'D as supplemental therapy for pneumocystis pneumonia. Antimicrob Agents '
'Chemother 61(10):e01226–e01217. https://doi.org/10.1128/aac.01226-17',
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'Maddock J, Hyppönen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler '
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'II-exposed microglial cells: role of renin-angiotensin system. Redox '
'Biol 26:101295. https://doi.org/10.1016/j.redox.2019.101295',
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'Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, '
'Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, '
'Urashima M, Camargo CA Jr (2017) Vitamin D supplementation to prevent '
'acute respiratory tract infections: systematic review and meta-analysis '
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'Fraser WD, Christopher KB, Cooper MS, Gao F, Sansom DM, Martineau AR, '
'Perkins GD, Thickett DR (2015) Vitamin D deficiency contributes directly '
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'post-treatment suppresses inflammatory response to influenza A (H1N1) '
'infection in human lung A549 epithelial cells. Eur J Nutr '
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