Prevalence and Clinical Outcomes of Vitamin D Deficiency in COVID-19 Hospitalized Patients: A Retrospective Single-Center Analysis
Siamak Afaghi, Farzad Esmaeili Tarki, Fatemeh Sadat Rahimi, Sara Besharat, Shayda Mirhaidari, Anita Karimi, Vascular Nasser Malekpour Alamdari
The Tohoku Journal of Experimental Medicine, doi:10.1620/tjem.255.127
Vitamin D attenuates inflammatory responses to viral respiratory infections. Hence, vitamin D deficiency may be a highly significant prognostic factor for severity and mortality in COVID-19 patients. To evaluate the complications and mortality in different vitamin D status groups in COVID-19 hospitalized patients, we conducted this retrospective study on 646 laboratory-confirmed COVID-19 patients who were hospitalized in Shahid Modarres Hospital, Tehran, Iran from 16th March 2020 until 25th February 2021. Overall, patients with vitamin D deficiency, insufficiency and sufficiency were 16.9%, 43.6% and 39.5%, respectively. The presence of comorbidity, length of hospitalization, ICU admission, and invasive mechanical ventilation requirement and overall complications were significantly more in patients with vitamin D deficiency (p-value < 0.001). 46.8% (51/109) of vitamin D deficient patients died due to the disease, whilst the mortality rate among insufficient and sufficient vitamin D groups was 29.4% (83/282) and 5.5% (14/255), respectively. In univariate analysis, age > 60 years (odds ratio (OR) = 6.1), presence of comorbidity (OR = 10.7), insufficient vitamin D status (OR = 7.2), and deficient vitamin D status (OR = 15.1) were associated with increase in COVID-19 mortality (p-value < 0.001). Finally, the multivariate analysis adjusted for age, sex, and comorbidities indicated vitamin D deficiency as an independent risk factor for mortality (OR = 3.3, p-value = 0.002). Vitamin D deficiency is a strong risk factor for mortality and severity of SARS-CoV-2 infection. Vitamin D supplementation may be able to prevent or improve the prognosis of COVID-19 during this pandemic.
References
Adams, Ren, Liu, Chun, Lagishetty et al., Vitamin D-directed rheostatic regulation of monocyte antibacterial responses, J. Immunol
Ali, Role of vitamin D in preventing of COVID-19 infection, progression and severity, J. Infect. Public Health
Aranow, Vitamin D and the immune system, J. Investig. Med
Beard, Bearden, Striker, Vitamin D and the anti-viral state, J. Clin. Virol
Berry, Hesketh, Power, Hyppönen, Vitamin D status has a linear association with seasonal infections and lung function in British adults, Br. J. Nutr
Bychinin, Klypa, Mandel, Andreichenko, Baklaushev et al., Low circulating vitamin D in intensive care unit-admitted COVID-19 patients as a predictor of negative outcomes, J. Nutr
Cantorna, Snyder, Lin, Yang, Vitamin D and 1,25(OH)2D regulation of T cells, Nutrients
Channappanavar, Perlman, Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Semin. Immunopathol
Chun, Liu, Modlin, Adams, Hewison, Impact of vitamin D on immune function: lessons learned from genome-wide analysis, Front. Physiol
Fisher, Rahimzadeh, Brierley, Gration, Doree et al., The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: a systematic review, PLoS One
Gattinoni, Chiumello, Rossi, COVID-19 pneumonia: ARDS or not?, Crit. Care
Gouni-Berthold, Krone, Berthold, Vitamin D and cardiovascular disease, Curr. Vasc. Pharmacol
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients
Gunville, Mourani, Ginde, The role of vitamin D in prevention and treatment of infection, Inflamm. Allergy Drug Targets
Hii, Ferrante, The non-genomic actions of vitamin D, Nutrients
Hong, Xiong, Huang, Wu, Lin et al., Association of vitamin D supplementation with respiratory tract infection in infants, Matern. Child Nutr
Huang, Zhang, Liu, Zhao, Zhang et al., Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virusinduced lung injury, PLoS Pathog
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin. Exp. Res
Jakovac, COVID-19 and vitamin D-is there a link and an opportunity for intervention?, Am. J. Physiol. Endocrinol. Metab
Jolliffe, Griffiths, Martineau, Vitamin D in the prevention of acute respiratory infection: systematic review of clinical studies, J. Steroid Biochem. Mol. Biol
Joshi, Pantalena, Liu, Gaffen, Liu et al., 1, 25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A, Mol. Cell. Biol
Laaksi, Vitamin D and respiratory infection in adults, Proc. Nutr. Soc
Le, Andreadakis, Kumar, Gomez Roman, Tollefsen et al., The COVID-19 vaccine development landscape, Nat. Rev. Drug Discov
Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science
Marik, Kory, Varon, Does vitamin D status impact mortality from SARS-CoV-2 infection?, Med. Drug. Discov
Prietl, Treiber, Pieber, Amrein, Vitamin D and immune function, Nutrients
Raharusun, Priambada, Budiarti, Agung, Budi, Patterns of COVID-19 mortality and vitamin D: an Indonesian study
Shi, Liu, Yao, Xing, Zhao et al., Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system, Sci. Rep
Sizar, Khare, Goyal, Bansal, Givler, Vitamin D deficiency
Talebi, Rasooli Nejad, Yaseri, Hadadi, Association of vitamin D status with the severity and mortality of community-acquired pneumonia in Iran during 2016-2017: a prospective cohort study, Rep. Biochem. Mol. Biol
Teymoori-Rad, Shokri, Salimi, Marashi, The interplay between vitamin D and viral infections, Rev. Med. Virol
Tsujino, Ushikoshi-Nakayama, Yamazaki, Matsumoto, Saito, Pulmonary activation of vitamin D3 and preventive effect against interstitial pneumonia, J. Clin. Biochem. Nutr
Watkins, Lemonovich, Salata, An update on the association of vitamin D deficiency with common infectious diseases, Can. J. Physiol. Pharmacol
Watkins, Yamshchikov, Lemonovich, Salata, The role of vitamin D deficiency in sepsis and potential therapeutic implications, J. Infect
Wimalawansa, Vitamin D deficiency: effects on oxidative stress, epigenetics, gene regulation, and aging, Biology
Yamshchikov, Desai, Blumberg, Ziegler, Tangpricha, Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials, Endocr. Pract
Yao, Lu, Chen, Xu, Chen et al., A pathological report of three COVID-19 cases by minimal invasive autopsies, Zhonghua Bing Li Xue Za Zhi,
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'author': [ { 'given': 'Siamak',
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'member': '622',
'reference': [ { 'key': '1',
'doi-asserted-by': 'crossref',
'unstructured': 'Adams, J.S., Ren, S., Liu, P.T., Chun, R.F., Lagishetty, V., Gombart, '
'A.F., Borregaard, N., Modlin, R.L. & Hewison, M.(2009) Vitamin '
'D-directed rheostatic regulation of monocyte antibacterial responses. '
'<i>J. Immunol</i>., 182, 4289-4295.',
'DOI': '10.4049/jimmunol.0803736'},
{ 'key': '2',
'doi-asserted-by': 'crossref',
'unstructured': 'Ali, N. (2020) Role of vitamin D in preventing of COVID-19 infection, '
'progression and severity. <i>J. Infect. Public Health</i>, 13, '
'1373-1380.',
'DOI': '10.1016/j.jiph.2020.06.021'},
{ 'key': '3',
'doi-asserted-by': 'crossref',
'unstructured': 'Aranow, C. (2011) Vitamin D and the immune system. <i>J. Investig. '
'Med</i>., 59, 881-886.',
'DOI': '10.2310/JIM.0b013e31821b8755'},
{ 'key': '4',
'doi-asserted-by': 'crossref',
'unstructured': 'Beard, J.A., Bearden, A. & Striker, R.(2011) Vitamin D and the '
'anti-viral state. <i>J. Clin. Virol</i>., 50, 194-200.',
'DOI': '10.1016/j.jcv.2010.12.006'},
{ 'key': '5',
'doi-asserted-by': 'crossref',
'unstructured': 'Berry, D.J., Hesketh, K., Power, C. & Hyppönen, E.(2011) Vitamin D '
'status has a linear association with seasonal infections and lung '
'function in British adults. <i>Br. J. Nutr</i>., 106, 1433-1440.',
'DOI': '10.1017/S0007114511001991'},
{ 'key': '6',
'doi-asserted-by': 'crossref',
'unstructured': 'Bychinin, M.V., Klypa, T.V., Mandel, I.A., Andreichenko, S.A., '
'Baklaushev, V.P., Yusubalieva, G.M., Kolyshkina, N.A. & Troitsky, '
'A.V.(2021) Low circulating vitamin D in intensive care unit-admitted '
'COVID-19 patients as a predictor of negative outcomes. <i>J. Nutr</i>., '
'151, 2199-2205.',
'DOI': '10.1093/jn/nxab107'},
{ 'key': '7',
'doi-asserted-by': 'crossref',
'unstructured': 'Cantorna, M.T., Snyder, L., Lin, Y.D. & Yang, L.(2015) Vitamin D '
'and 1,25(OH)2D regulation of T cells. <i>Nutrients</i>, 7, 3011-3021.',
'DOI': '10.3390/nu7043011'},
{ 'key': '8',
'doi-asserted-by': 'crossref',
'unstructured': 'Channappanavar, R. & Perlman, S.(2017) Pathogenic human coronavirus '
'infections: causes and consequences of cytokine storm and '
'immunopathology. <i>Semin. Immunopathol</i>., 39, 529-539.',
'DOI': '10.1007/s00281-017-0629-x'},
{ 'key': '9',
'doi-asserted-by': 'crossref',
'unstructured': 'Chun, R.F., Liu, P.T., Modlin, R.L., Adams, J.S. & Hewison, '
'M.(2014) Impact of vitamin D on immune function: lessons learned from '
'genome-wide analysis. <i>Front. Physiol</i>., 5, 151.',
'DOI': '10.3389/fphys.2014.00151'},
{ 'key': '10',
'doi-asserted-by': 'crossref',
'unstructured': 'Fisher, S.A., Rahimzadeh, M., Brierley, C., Gration, B., Doree, C., '
'Kimber, C.E., Plaza Cajide, A., Lamikanra, A.A. & Roberts, '
'D.J.(2019) The role of vitamin D in increasing circulating T regulatory '
'cell numbers and modulating T regulatory cell phenotypes in patients '
'with inflammatory disease or in healthy volunteers: a systematic '
'review. <i>PLoS One</i>, 14, e0222313.',
'DOI': '10.1371/journal.pone.0222313'},
{ 'key': '11',
'doi-asserted-by': 'crossref',
'unstructured': 'Gattinoni, L., Chiumello, D. & Rossi, S.(2020) COVID-19 pneumonia: '
'ARDS or not? <i>Crit. Care</i>, 24, 154.',
'DOI': '10.1186/s13054-020-02880-z'},
{ 'key': '12',
'doi-asserted-by': 'crossref',
'unstructured': 'Gouni-Berthold, I., Krone, W. & Berthold, H.K.(2009) Vitamin D and '
'cardiovascular disease. <i>Curr. Vasc. Pharmacol</i>., 7, 414-422.',
'DOI': '10.2174/157016109788340686'},
{ 'key': '13',
'doi-asserted-by': 'crossref',
'unstructured': 'Grant, W.B., Lahore, H., McDonnell, S.L., Baggerly, C.A., French, C.B., '
'Aliano, J.L. & Bhattoa, H.P.(2020) Evidence that vitamin D '
'supplementation could reduce risk of influenza and COVID-19 infections '
'and deaths. <i>Nutrients</i>, 12, 988.',
'DOI': '10.3390/nu12040988'},
{ 'key': '14',
'doi-asserted-by': 'crossref',
'unstructured': 'Gunville, C.F., Mourani, P.M. & Ginde, A.A.(2013) The role of '
'vitamin D in prevention and treatment of infection. <i>Inflamm. Allergy '
'Drug Targets</i>, 12, 239-245.',
'DOI': '10.2174/18715281113129990046'},
{ 'key': '15',
'doi-asserted-by': 'crossref',
'unstructured': 'Hii, C.S. & Ferrante, A.(2016) The non-genomic actions of vitamin '
'D. <i>Nutrients</i>, 8, 135.',
'DOI': '10.3390/nu8030135'},
{ 'key': '16',
'doi-asserted-by': 'crossref',
'unstructured': 'Hong, M., Xiong, T., Huang, J., Wu, Y., Lin, L., Zhang, Z., Huang, L., '
'Gao, D., Wang, H., Kang, C., Gao, Q., Yang, X., Yang, N. & Hao, '
'L.(2020) Association of vitamin D supplementation with respiratory '
'tract infection in infants. <i>Matern. Child Nutr</i>., 16, e12987.',
'DOI': '10.1111/mcn.12987'},
{ 'key': '17',
'doi-asserted-by': 'crossref',
'unstructured': 'Huang, F., Zhang, C., Liu, Q., Zhao, Y., Zhang, Y., Qin, Y., Li, X., Li, '
'C., Zhou, C., Jin, N. & Jiang, C.(2020) Identification of '
'amitriptyline HCl, flavin adenine dinucleotide, azacitidine and '
'calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung '
'injury. <i>PLoS Pathog</i>, 16, e1008341.',
'DOI': '10.1371/journal.ppat.1008341'},
{ 'key': '18',
'doi-asserted-by': 'crossref',
'unstructured': 'Ilie, P.C., Stefanescu, S. & Smith, L.(2020) The role of vitamin D '
'in the prevention of coronavirus disease 2019 infection and mortality. '
'<i>Aging Clin. Exp. Res</i>., 32, 1195-1198.',
'DOI': '10.1007/s40520-020-01570-8'},
{ 'key': '19',
'doi-asserted-by': 'crossref',
'unstructured': 'Jakovac, H. (2020) COVID-19 and vitamin D-is there a link and an '
'opportunity for intervention? <i>Am. J. Physiol. Endocrinol. '
'Metab</i>., 318, E589.',
'DOI': '10.1152/ajpendo.00138.2020'},
{ 'key': '20',
'doi-asserted-by': 'crossref',
'unstructured': 'Jolliffe, D.A., Griffiths, C.J. & Martineau, A.R.(2013) Vitamin D '
'in the prevention of acute respiratory infection: systematic review of '
'clinical studies. <i>J. Steroid Biochem. Mol. Biol</i>., 136, 321-329.',
'DOI': '10.1016/j.jsbmb.2012.11.017'},
{ 'key': '21',
'doi-asserted-by': 'crossref',
'unstructured': 'Joshi, S., Pantalena, L.C., Liu, X.K., Gaffen, S.L., Liu, H., '
'Rohowsky-Kochan, C., Ichiyama, K., Yoshimura, A., Steinman,L. & '
'Christakos, S.(2011) 1, 25-Dihydroxyvitamin D3 ameliorates Th17 '
'autoimmunity via transcriptional modulation of interleukin-17A. <i>Mol. '
'Cell. Biol</i>., 31, 3653-3669.',
'DOI': '10.1128/MCB.05020-11'},
{ 'key': '22',
'doi-asserted-by': 'crossref',
'unstructured': 'Laaksi, I. (2012) Vitamin D and respiratory infection in adults. '
'<i>Proc. Nutr. Soc</i>., 71, 90-97.',
'DOI': '10.1017/S0029665111003351'},
{ 'key': '23',
'doi-asserted-by': 'crossref',
'unstructured': 'Liu, P.T., Stenger, S., Li, H., Wenzel, L., Tan, B.H., Krutzik, S.R., '
'Ochoa, M.T., Schauber, J., Wu, K., Meinken, C., Kamen, D.L., Wagner, M., '
'Bals, R., Steinmeyer, A., Zugel, U., et al. (2006) Toll-like receptor '
'triggering of a vitamin D-mediated human antimicrobial response. '
'<i>Science</i>, 311, 1770-1773.',
'DOI': '10.1126/science.1123933'},
{ 'key': '24',
'doi-asserted-by': 'crossref',
'unstructured': 'Marik, P.E., Kory,P. & Varon, J.(2020) Does vitamin D status impact '
'mortality from SARS-CoV-2 infection? <i>Med. Drug. Discov</i>., 6, '
'100041.',
'DOI': '10.1016/j.medidd.2020.100041'},
{ 'key': '25',
'doi-asserted-by': 'crossref',
'unstructured': 'Prietl, B., Treiber, G., Pieber, T.R. & Amrein, K.(2013) Vitamin D '
'and immune function. <i>Nutrients</i>, 5, 2502-2521.',
'DOI': '10.3390/nu5072502'},
{ 'key': '26',
'doi-asserted-by': 'crossref',
'unstructured': 'Raharusun, P., Priambada, S., Budiarti, C., Agung, E. & Budi, '
'C.(2020) Patterns of COVID-19 mortality and vitamin D: an Indonesian '
'study. '
'https://emerginnova.com/patterns-of-covid19-mortality-and-vitamin-d-an-indonesian-study/ '
'[Accessed: April 26, 2020].',
'DOI': '10.2139/ssrn.3585561'},
{ 'key': '27',
'doi-asserted-by': 'crossref',
'unstructured': 'Shi, Y., Liu, T., Yao, L., Xing, Y., Zhao, X., Fu,J. & Xue, '
'X.(2017) Chronic vitamin D deficiency induces lung fibrosis through '
'activation of the renin-angiotensin system. <i>Sci. Rep</i>., 7, 3312.',
'DOI': '10.1038/s41598-017-03474-6'},
{ 'key': '28',
'unstructured': 'Sizar, O., Khare, S., Goyal, A., Bansal, P. & Givler, A.(2021) '
'Vitamin D deficiency. In <i>StatPearls</i>, Treasure Island, FL.'},
{ 'key': '29',
'unstructured': 'Talebi, F., Rasooli Nejad, M., Yaseri, M. & Hadadi, A.(2019) '
'Association of vitamin D status with the severity and mortality of '
'community-acquired pneumonia in Iran during 2016-2017: a prospective '
'cohort study. <i>Rep. Biochem. Mol. Biol.</i>, 8, 85-90.'},
{ 'key': '30',
'doi-asserted-by': 'crossref',
'unstructured': 'Teymoori-Rad, M., Shokri, F., Salimi, V. & Marashi, S.M.(2019) The '
'interplay between vitamin D and viral infections. <i>Rev. Med. '
'Virol.</i>, 29, e2032.',
'DOI': '10.1002/rmv.2032'},
{ 'key': '31',
'doi-asserted-by': 'crossref',
'unstructured': 'Thanh Le, T., Andreadakis, Z., Kumar, A., Gomez Roman, R., Tollefsen, '
'S., Saville, M. & Mayhew, S.(2020) The COVID-19 vaccine development '
'landscape. <i>Nat. Rev. Drug Discov.</i>, 19, 305-306.',
'DOI': '10.1038/d41573-020-00073-5'},
{ 'key': '32',
'doi-asserted-by': 'crossref',
'unstructured': 'Tsujino, I., Ushikoshi-Nakayama, R., Yamazaki, T., Matsumoto, N. & '
'Saito, I.(2019) Pulmonary activation of vitamin D3 and preventive '
'effect against interstitial pneumonia. <i>J. Clin. Biochem. Nutr.</i>, '
'65, 245-251.',
'DOI': '10.3164/jcbn.19-48'},
{ 'key': '33',
'doi-asserted-by': 'crossref',
'unstructured': 'Watkins, R.R., Lemonovich, T.L. & Salata, R.A.(2015) An update on '
'the association of vitamin D deficiency with common infectious '
'diseases. <i>Can. J. Physiol. Pharmacol.</i>, 93, 363-368.',
'DOI': '10.1139/cjpp-2014-0352'},
{ 'key': '34',
'doi-asserted-by': 'crossref',
'unstructured': 'Watkins, R.R., Yamshchikov, A.V., Lemonovich, T.L. & Salata, '
'R.A.(2011) The role of vitamin D deficiency in sepsis and potential '
'therapeutic implications. <i>J. Infect.</i>, 63, 321-326.',
'DOI': '10.1016/j.jinf.2011.07.002'},
{ 'key': '35',
'doi-asserted-by': 'crossref',
'unstructured': 'Wimalawansa, S.J. (2019) Vitamin D deficiency: effects on oxidative '
'stress, epigenetics, gene regulation, and aging. <i>Biology</i> '
'(<i>Basel</i>), 8, 30.',
'DOI': '10.3390/biology8020030'},
{ 'key': '36',
'unstructured': 'World Health Organization (2020) Clinical management of severe acute '
'respiratory infection (SARI) when COVID-19 disease is suspected: '
'interim guidance, 13 March 2020. '
'https://scholar.googleusercontent.com/scholar?q=cache:RNffJn6imTEJ:scholar.google.com/+World+Health+Organization+(2020)+Clinical+management+of+severe+acute+respiratory+infection+(SARI)+when+COVID-19+disease+is+suspected:+interim+guidance,+13+March+2020.&hl=en&as_sdt=0,5 '
'[Accessed: March 13, 2020].'},
{ 'key': '37',
'doi-asserted-by': 'publisher',
'unstructured': 'Wu, R., Wang, L., Kuo, H.D., Shannar, A., Peter, R., Chou, P.J., Li, S., '
'Hudlikar, R., Liu, X., Liu, Z., Poiani, G.J., Amorosa, L., Brunetti, L. '
'& Kong, A.N.(2020) An update on current therapeutic drugs treating '
'COVID-19. <i>Curr. Pharmacol. Rep.</i>, doi:10.1007/s40495-020-00216-7. '
'[Epub ahead of print].',
'DOI': '10.1007/s40495-020-00216-7'},
{ 'key': '38',
'doi-asserted-by': 'crossref',
'unstructured': 'Yamshchikov, A.V., Desai, N.S., Blumberg, H.M., Ziegler, T.R. & '
'Tangpricha, V.(2009) Vitamin D for treatment and prevention of '
'infectious diseases: a systematic review of randomized controlled '
'trials. <i>Endocr. Pract.</i>, 15, 438-449.',
'DOI': '10.4158/EP09101.ORR'},
{ 'key': '39',
'doi-asserted-by': 'crossref',
'unstructured': 'Yao, H., Lu, X., Chen, Q., Xu, K., Chen, Y., Cheng, L., Liu, F., Wu, Z., '
'Wu, H., Jin, C., Zheng, M., Wu, N., Jiang, C. & Li, L.(2020a) '
'Patient-derived mutations impact pathogenicity of SARS-CoV-2. '
'<i>medRxiv</i>, doi.org/10.1101/2020.04.14.20060160.',
'DOI': '10.1101/2020.04.14.20060160'},
{ 'key': '40',
'unstructured': 'Yao, X.H., Li, T.Y., He, Z.C., Ping, Y.F., Liu, H.W., Yu, S.C., Mou, '
'H.M., Wang, L.H., Zhang, H.R., Fu, W.J., Luo, T., Liu, F., Guo, Q.N., '
'Chen, C., Xiao, H.L., et al. (2020b) A pathological report of three '
'COVID-19 cases by minimal invasive autopsies. <i>Zhonghua Bing Li Xue '
'Za Zhi</i>, 49, 411-417.'}],
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'references-count': 40,
'journal-issue': {'issue': '2', 'published-print': {'date-parts': [[2021]]}},
'URL': 'http://dx.doi.org/10.1620/tjem.255.127',
'relation': {},
'ISSN': ['0040-8727', '1349-3329'],
'subject': ['General Biochemistry, Genetics and Molecular Biology', 'General Medicine'],
'container-title-short': 'Tohoku J. Exp. Med.',
'published': {'date-parts': [[2021]]}}
