The Association Between Vitamin D Serum Level and COVID-19 Patients’ Outcomes in a Tertiary Center in Saudi Arabia: A Retrospective Cohort Study
Mahmoud A Alzahrani, Faisal Almalki, Ayman Aljohani, Bassam Alharbi, Bandar Alsulami, Ahmed Alhaddad, Alaa Althubaiti, Bader Khawaji, Fayssal Farahat
Cureus, doi:10.7759/cureus.26266
Vitamin D deficiency has been associated with the risk for immune-mediated inflammatory reactions in various respiratory infections. Our study investigated the association between vitamin D deficiency and coronavirus disease 2019 (COVID-19) patients' outcomes. We included 545 patients who were admitted to a tertiary center in Jeddah, Saudi Arabia from March 2020 to July 2021 with a vitamin D serum test result at the time of infection or prior to disease onset. The data were extracted retrospectively using a data collection sheet. Our primary outcomes were intensive care unit (ICU) admission and in-hospital mortality. The cut-off values for vitamin D were <25, 25-49, and 50-250 for deficient, suboptimal, and optimal levels respectively. Our result revealed that there is no association between vitamin D serum levels deficiency and ICU admission (OR=1.08, p=0.75) or in-hospital mortality (OR=1.74, p=0.97). ICU admission and in-hospital mortality percentages in patients with vitamin D deficiency were 14.1% and 6.4%, respectively. In comparison, percentages for patients with optimal levels were 16.67% and 6.15% for ICU admission and inhospital mortality, respectively. Smoking was not associated with ICU admission (p=0.05) or in-hospital mortality (p=0.38). Our study does not support a relationship between vitamin D deficiency and COVID-19 patients' outcomes. Future studies should be directed toward conducting randomized clinical trials to determine whether vitamin D has an effective role in reducing COVID-19 severity.
Additional Information Disclosures Human subjects: Consent was obtained or waived by all participants in this study. King Abdullah International Medical Research Center (KAIMRC) issued approval SP21J/251/05. "After reviewing your submitted research proposal/protocol and related documents, the IRB has APPROVED the submission". Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
References
Abrishami, Dalili, Torbati, Asgari, Arab-Ahmadi et al., Possible association of vitamin D status with lung involvement and outcome in patients with COVID-19: a retrospective study, Eur J Nutr,
doi:10.1007/s00394-020-02411-0
Al-Alyani, Ha, On, Alani, Sadat-Ali, Vitamin D deficiency in Saudi Arabians: a reality or simply hype: a meta-analysis (2008-2015), J Family Community Med,
doi:10.4103/jfcm.JFCM_73_17
Alkhafaji, Argan, Albaker, The impact of vitamin D level on the severity and outcome of hospitalized patients with COVID-19 disease, Int J Gen Med,
doi:10.2147/IJGM.S346169
Bishop, Ismailova, Dimeloe, Hewison, White, Vitamin D and immune regulation: antibacterial, antiviral, anti-inflammatory, JBMR Plus,
doi:10.1002/jbm4.10405
Cereda, Bogliolo, Klersy, Vitamin D 25OH deficiency in COVID-19 patients admitted to a tertiary referral hospital, Clin Nutr,
doi:10.1016/j.clnu.2020.10.055
Chen, Wu, Guo, Clinical and immunological features of severe and moderate coronavirus disease 2019, J Clin Invest,
doi:10.1172/JCI137244
Daneshkhah, Agrawal, Eshein, Subramanian, Roy et al., Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients, Aging Clin Exp Res,
doi:10.1007/s40520-020-01677-y
Inamo, Hasegawa, Saito, Serum vitamin D concentrations and associated severity of acute lower respiratory tract infections in Japanese hospitalized children, Pediatr Int,
doi:10.1111/j.1442-200x.2010.03224.x
Laird, Mcnulty, Ward, Vitamin D deficiency is associated with inflammation in older Irish adults, J Clin Endocrinol Metab,
doi:10.1210/jc.2013-3507
Mutair, Alhumaid, Alhuqbani, Clinical, epidemiological, and laboratory characteristics of mild-to-moderate COVID-19 patients in Saudi Arabia: an observational cohort study, Eur J Med Res,
doi:10.1186/s40001-020-00462-x
Pereira, Damascena, Azevedo, De Almeida Oliveira, Da et al., Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis, Crit Rev Food Sci Nutr,
doi:10.1080/10408398.2020.1841090
Rabenberg, Scheidt-Nave, Busch, Rieckmann, Hintzpeter et al., Vitamin D status among adults in Germany--results from the German Health Interview and Examination Survey for Adults (DEGS1), BMC Public Health,
doi:10.1186/s12889-015-2016-7
Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger, Vitamin D deficiency and outcome of COVID-19 patients, Nutrients,
doi:10.3390/nu12092757
{ 'indexed': {'date-parts': [[2022, 6, 24]], 'date-time': '2022-06-24T11:12:11Z', 'timestamp': 1656069131774},
'reference-count': 23,
'publisher': 'Cureus, Inc.',
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2022, 6, 23]]},
'DOI': '10.7759/cureus.26266',
'type': 'journal-article',
'created': {'date-parts': [[2022, 6, 23]], 'date-time': '2022-06-23T21:49:49Z', 'timestamp': 1656020989000},
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'The Association Between Vitamin D Serum Level and COVID-19 Patients’ Outcomes in a Tertiary '
'Center in Saudi Arabia: A Retrospective Cohort Study',
'prefix': '10.7759',
'author': [ {'given': 'Mahmoud A', 'family': 'Alzahrani', 'sequence': 'first', 'affiliation': []},
{'given': 'Faisal', 'family': 'Almalki', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ayman', 'family': 'Aljohani', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bassam', 'family': 'Alharbi', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bandar', 'family': 'Alsulami', 'sequence': 'additional', 'affiliation': []},
{'given': 'Ahmed', 'family': 'Alhaddad', 'sequence': 'additional', 'affiliation': []},
{'given': 'Alaa', 'family': 'Althubaiti', 'sequence': 'additional', 'affiliation': []},
{'given': 'Bader', 'family': 'Khawaji', 'sequence': 'additional', 'affiliation': []},
{'given': 'Fayssal', 'family': 'Farahat', 'sequence': 'additional', 'affiliation': []}],
'member': '4492',
'reference': [ { 'key': 'ref1',
'doi-asserted-by': 'publisher',
'DOI': '10.3390/nu5072502',
'article-title': 'Vitamin D and immune function',
'volume': '5',
'author': 'Prietl B',
'year': '2013',
'unstructured': 'Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. '
'Nutrients. 2013, 5:2502-2521. 10.3390/nu5072502',
'journal-title': 'Nutrients'},
{ 'key': 'ref2',
'doi-asserted-by': 'publisher',
'DOI': '10.1002/jbm4.10405',
'article-title': 'Vitamin D and immune regulation: antibacterial, antiviral, '
'anti-inflammatory',
'volume': '5',
'author': 'Bishop E',
'year': '2020',
'unstructured': 'Bishop E, Ismailova A, Dimeloe SK, Hewison M, White JH. Vitamin D and '
'immune regulation: antibacterial, antiviral, anti-inflammatory. JBMR '
'Plus. 2020, 5:e10405. 10.1002/jbm4.10405',
'journal-title': 'JBMR Plus'},
{ 'key': 'ref3',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMra070553',
'article-title': 'Vitamin D deficiency',
'volume': '357',
'author': 'Holick MF',
'year': '2007',
'unstructured': 'Holick MF. Vitamin D deficiency. N Engl J Med. 2007, 357:266-281. '
'10.1056/NEJMra070553',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref4',
'doi-asserted-by': 'publisher',
'DOI': '10.1186/s12889-015-2016-7',
'article-title': 'Vitamin D status among adults in Germany--results from the German '
'Health Interview and Examination Survey for Adults (DEGS1)',
'volume': '15',
'author': 'Rabenberg M',
'year': '2015',
'unstructured': 'Rabenberg M, Scheidt-Nave C, Busch MA, Rieckmann N, Hintzpeter B, '
'Mensink GB. Vitamin D status among adults in Germany--results from the '
'German Health Interview and Examination Survey for Adults (DEGS1). BMC '
'Public Health. 2015, 15:641. 10.1186/s12889-015-2016-7',
'journal-title': 'BMC Public Health'},
{ 'key': 'ref5',
'doi-asserted-by': 'publisher',
'DOI': '10.1210/jc.2013-3507',
'article-title': 'Vitamin D deficiency is associated with inflammation in older Irish '
'adults',
'volume': '99',
'author': 'Laird E',
'year': '2014',
'unstructured': 'Laird E, McNulty H, Ward M, et al.. Vitamin D deficiency is associated '
'with inflammation in older Irish adults. J Clin Endocrinol Metab. 2014, '
'99:1807-1815. 10.1210/jc.2013-3507',
'journal-title': 'J Clin Endocrinol Metab'},
{ 'key': 'ref6',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/j.1442-200x.2010.03224.x',
'article-title': 'Serum vitamin D concentrations and associated severity of acute lower '
'respiratory tract infections in Japanese hospitalized children',
'volume': '53',
'author': 'Inamo Y',
'year': '2011',
'unstructured': 'Inamo Y, Hasegawa M, Saito K, et al.. Serum vitamin D concentrations and '
'associated severity of acute lower respiratory tract infections in '
'Japanese hospitalized children. Pediatr Int. 2011, 53:199-201. '
'10.1111/j.1442-200x.2010.03224.x',
'journal-title': 'Pediatr Int'},
{ 'key': 'ref7',
'doi-asserted-by': 'publisher',
'DOI': '10.1111/j.1398-9995.2011.02711.x',
'article-title': 'Asthma, allergy and respiratory infections: the vitamin D hypothesis',
'volume': '67',
'author': 'Bozzetto S',
'year': '2012',
'unstructured': 'Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E. Asthma, allergy '
'and respiratory infections: the vitamin D hypothesis. Allergy. 2012, '
'67:10-17. 10.1111/j.1398-9995.2011.02711.x',
'journal-title': 'Allergy'},
{ 'key': 'ref8',
'doi-asserted-by': 'publisher',
'DOI': '10.4103/jfcm.JFCM_73_17',
'article-title': 'Vitamin D deficiency in Saudi Arabians: a reality or simply hype: a '
'meta-analysis (2008-2015)',
'volume': '25',
'author': 'Al-Alyani H',
'year': '2018',
'unstructured': 'Al-Alyani H, Al-Turki HA, Al-Essa ON, Alani FM, Sadat-Ali M. Vitamin D '
'deficiency in Saudi Arabians: a reality or simply hype: a meta-analysis '
'(2008-2015). J Family Community Med. 2018, 25:1-4. '
'10.4103/jfcm.JFCM_73_17',
'journal-title': 'J Family Community Med'},
{ 'key': 'ref9',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.jsbmb.2016.12.017',
'article-title': 'Vitamin D in Saudi Arabia: prevalence, distribution and disease '
'associations',
'volume': '175',
'author': 'Al-Daghri NM',
'year': '2018',
'unstructured': 'Al-Daghri NM. Vitamin D in Saudi Arabia: prevalence, distribution and '
'disease associations. J Steroid Biochem Mol Biol. 2018, 175:102-107. '
'10.1016/j.jsbmb.2016.12.017',
'journal-title': 'J Steroid Biochem Mol Biol'},
{ 'key': 'ref10',
'doi-asserted-by': 'publisher',
'DOI': '10.2340/00015555-0980',
'article-title': 'Factors influencing vitamin D status',
'volume': '91',
'author': 'Tsiaras WG',
'year': '2011',
'unstructured': 'Tsiaras WG, Weinstock MA. Factors influencing vitamin D status. Acta '
'Derm Venereol. 2011, 91:115-124. 10.2340/00015555-0980',
'journal-title': 'Acta Derm Venereol'},
{ 'key': 'ref11',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.ijsu.2020.04.018',
'article-title': 'The socio-economic implications of the coronavirus pandemic (COVID-19): '
'a review',
'volume': '78',
'author': 'Nicola M',
'year': '2020',
'unstructured': 'Nicola M, Alsafi Z, Sohrabi C, et al.. The socio-economic implications '
'of the coronavirus pandemic (COVID-19): a review. Int J Surg. 2020, '
'78:185-193. 10.1016/j.ijsu.2020.04.018',
'journal-title': 'Int J Surg'},
{ 'key': 'ref12',
'doi-asserted-by': 'publisher',
'DOI': '10.1056/NEJMe2001126',
'article-title': 'Another decade, another coronavirus',
'volume': '382',
'author': 'Perlman S',
'year': '2020',
'unstructured': 'Perlman S. Another decade, another coronavirus. N Engl J Med. 2020, '
'382:760-762. 10.1056/NEJMe2001126',
'journal-title': 'N Engl J Med'},
{ 'key': 'ref13',
'doi-asserted-by': 'publisher',
'DOI': '10.1038/s41591-020-01202-8',
'article-title': 'Immune determinants of COVID-19 disease presentation and severity',
'volume': '27',
'author': 'Brodin P',
'year': '2021',
'unstructured': 'Brodin P. Immune determinants of COVID-19 disease presentation and '
'severity. Nat Med. 2021, 27:28-33. 10.1038/s41591-020-01202-8',
'journal-title': 'Nat Med'},
{ 'key': 'ref14',
'doi-asserted-by': 'publisher',
'DOI': '10.1172/JCI137244',
'article-title': 'Clinical and immunological features of severe and moderate coronavirus '
'disease 2019',
'volume': '130',
'author': 'Chen G',
'year': '2020',
'unstructured': 'Chen G, Wu D, Guo W, et al.. Clinical and immunological features of '
'severe and moderate coronavirus disease 2019. J Clin Invest. 2020, '
'130:2620-2629. 10.1172/JCI137244',
'journal-title': 'J Clin Invest'},
{ 'key': 'ref15',
'doi-asserted-by': 'publisher',
'DOI': '10.1007/s40520-020-01677-y',
'article-title': 'Evidence for possible association of vitamin D status with cytokine '
'storm and unregulated inflammation in COVID-19 patients',
'volume': '32',
'author': 'Daneshkhah A',
'year': '2020',
'unstructured': '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, 32:2141-2158. 10.1007/s40520-020-01677-y',
'journal-title': 'Aging Clin Exp Res'},
{ 'key': 'ref16',
'doi-asserted-by': 'publisher',
'DOI': '10.1080/10408398.2020.1841090',
'article-title': 'Vitamin D deficiency aggravates COVID-19: systematic review and '
'meta-analysis',
'volume': '62',
'author': 'Pereira M',
'year': '2022',
'unstructured': '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, 62:1308-1316. '
'10.1080/10408398.2020.1841090',
'journal-title': 'Crit Rev Food Sci Nutr'},
{ 'key': 'ref17',
'doi-asserted-by': 'publisher',
'DOI': '10.2147/IJGM.S346169',
'article-title': 'The impact of vitamin D level on the severity and outcome of '
'hospitalized patients with COVID-19 disease',
'volume': '15',
'author': 'AlKhafaji D',
'year': '2022',
'unstructured': 'AlKhafaji D, Al Argan R, Albaker W, et al.. The impact of vitamin D '
'level on the severity and outcome of hospitalized patients with COVID-19 '
'disease. Int J Gen Med. 2022, 15:343-352. 10.2147/IJGM.S346169',
'journal-title': 'Int J Gen Med'},
{ 'key': 'ref18',
'doi-asserted-by': 'publisher',
'DOI': '10.3390/nu12092757',
'article-title': 'Vitamin D deficiency and outcome of COVID-19 patients',
'volume': '12',
'author': 'Radujkovic A',
'year': '2020',
'unstructured': 'Radujkovic A, Hippchen T, Tiwari-Heckler S, Dreher S, Boxberger M, Merle '
'U. Vitamin D deficiency and outcome of COVID-19 patients. Nutrients. '
'2020, 12:2757. 10.3390/nu12092757',
'journal-title': 'Nutrients'},
{ 'key': 'ref19',
'doi-asserted-by': 'publisher',
'DOI': '10.1007/s00394-020-02411-0',
'article-title': 'Possible association of vitamin D status with lung involvement and '
'outcome in patients with COVID-19: a retrospective study',
'volume': '60',
'author': 'Abrishami A',
'year': '2021',
'unstructured': 'Abrishami A, Dalili N, Mohammadi Torbati P, Asgari R, Arab-Ahmadi M, '
'Behnam B, Sanei-Taheri M. Possible association of vitamin D status with '
'lung involvement and outcome in patients with COVID-19: a retrospective '
'study. Eur J Nutr. 2021, 60:2249-2257. 10.1007/s00394-020-02411-0',
'journal-title': 'Eur J Nutr'},
{ 'key': 'ref20',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.clnu.2020.10.055',
'article-title': 'Vitamin D 25OH deficiency in COVID-19 patients admitted to a tertiary '
'referral hospital',
'volume': '40',
'author': 'Cereda E',
'year': '2021',
'unstructured': 'Cereda E, Bogliolo L, Klersy C, et al.. Vitamin D 25OH deficiency in '
'COVID-19 patients admitted to a tertiary referral hospital. Clin Nutr. '
'2021, 40:2469-2472. 10.1016/j.clnu.2020.10.055',
'journal-title': 'Clin Nutr'},
{ 'key': 'ref21',
'doi-asserted-by': 'publisher',
'DOI': '10.1080/07435800.2020.1867162',
'article-title': 'Vitamin D status and COVID-19 clinical outcomes in hospitalized '
'patients',
'volume': '46',
'author': 'Szeto B',
'year': '2021',
'unstructured': 'Szeto B, Zucker JE, LaSota ED, Rubin MR, Walker MD, Yin MT, Cohen A. '
'Vitamin D status and COVID-19 clinical outcomes in hospitalized '
'patients. Endocr Res. 2021, 46:66-73. 10.1080/07435800.2020.1867162',
'journal-title': 'Endocr Res'},
{ 'key': 'ref22',
'doi-asserted-by': 'publisher',
'DOI': '10.1016/j.dsx.2020.04.050',
'article-title': 'Vitamin D concentrations and COVID-19 infection in UK Biobank',
'volume': '14',
'author': 'Hastie CE',
'year': '2020',
'unstructured': 'Hastie CE, Mackay DF, Ho F, et al.. Vitamin D concentrations and '
'COVID-19 infection in UK Biobank. Diabetes Metab Syndr. 2020, '
'14:561-565. 10.1016/j.dsx.2020.04.050',
'journal-title': 'Diabetes Metab Syndr'},
{ 'key': 'ref23',
'doi-asserted-by': 'publisher',
'DOI': '10.1186/s40001-020-00462-x',
'article-title': 'Clinical, epidemiological, and laboratory characteristics of '
'mild-to-moderate COVID-19 patients in Saudi Arabia: an observational '
'cohort study',
'volume': '25',
'author': 'Al Mutair A',
'year': '2020',
'unstructured': 'Al Mutair A, Alhumaid S, Alhuqbani WN, et al.. Clinical, '
'epidemiological, and laboratory characteristics of mild-to-moderate '
'COVID-19 patients in Saudi Arabia: an observational cohort study. Eur J '
'Med Res. 2020, 25:61. 10.1186/s40001-020-00462-x',
'journal-title': 'Eur J Med Res'}],
'container-title': 'Cureus',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://www.cureus.com/articles/96331-the-association-between-vitamin-d-serum-level-and-covid-19-patients-outcomes-in-a-tertiary-center-in-saudi-arabia-a-retrospective-cohort-study',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2022, 6, 23]],
'date-time': '2022-06-23T21:49:52Z',
'timestamp': 1656020992000},
'score': 1,
'resource': { 'primary': { 'URL': 'https://www.cureus.com/articles/96331-the-association-between-vitamin-d-serum-level-and-covid-19-patients-outcomes-in-a-tertiary-center-in-saudi-arabia-a-retrospective-cohort-study'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 6, 23]]},
'references-count': 23,
'URL': 'http://dx.doi.org/10.7759/cureus.26266',
'relation': {},
'ISSN': ['2168-8184'],
'subject': ['Aerospace Engineering'],
'published': {'date-parts': [[2022, 6, 23]]}}