Vitamin D deficiency predicts 30-day hospital mortality of adults with COVID-19
Fabio Fernandes Neves, Henrique Pott-Junior, Sigrid De Sousa Santos, Marcia Regina Cominetti, Caio Cesar De Melo Freire, Anderson Ferreira Da Cunha, Alceu Afonso Jordão Júnior
Clinical Nutrition ESPEN, doi:10.1016/j.clnesp.2022.05.027
Background & aims: Several studies have shown conflicting results for the relationship between vitamin D deficiency and COVID-19 outcomes. Here, we aimed to evaluate whether plasma 25(OH)D levels predict mortality in adults admitted with COVID-19, considering potential confounders. Methods: We conducted a retrospective cohort study that included 115 adults (age 62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Subjects were classified into two groups according to their plasma levels of 25(OH)D: sufficiency (50 nmol/L) and the deficiency (<50 nmol/L). The diagnosis of COVID-19 was performed using real-time polymerase chain reaction (qPCR). In addition, direct competitive chemiluminescence immunoassay assessed serum 25(OH)D levels. Results: The all-cause 30-day mortality was 13.8% (95% CI: 6.5%e21%) in the group of patients with sufficient plasma 25(OH)D levels and 32.1% (95% CI: 14.8%e49.4%) among those with deficient plasma 25(OH)D levels. Cox regression showed that plasma 25(OH)D levels remained a significant predictor of mortality even after adjusting for the covariates sex, age, length of the delay between symptom onset and hospitalization, and disease severity (HR ¼ 0.98, 95% CI: 0.96e1.00; p ¼ 0.02). Conclusion: Vitamin D deficiency predicts higher mortality risk in adults with COVID-19.
Author contributions Conceptualization, F.F.N. and H.P-J.; data curation, F.F.N., H.P-J. and S.S.S; formal analysis, F.F.N. and H.P-J.; funding acquisition, F.F.N.; investigation, F.F.N., H.P-J. and S.S.S; methodology, F.F.N., H.P-J., C.C.M.F, A.F.C. and A.A.J-J; resources, M.R.C., C.C.M.F, A.F.C. and A.A.J-J; software, H.P-J.; supervision, F.F.N. and H.P-J.; writing original draft, F.F.N. and H.P-J.; final approval: all authors.
Declaration of competing interest The authors declare no conflicts of interest.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.clnesp.2022.05.027.
References
Akbar, Wibowo, Pranata, Setiabudiawan, Low serum 25-hydroxyvitamin D (vitamin D) level is associated with susceptibility to COVID-19, severity, and mortality: a systematic review and meta-analysis, Front Nutr
Ali, Role of vitamin D in preventing of COVID-19 infection, progression and severity, J Infect Public Health
Banerjee, Ganguly, Saha, Chakrabarti, Saini et al., Vitamin D and immuno-pathology of COVID-19: many interactions but uncertain therapeutic benefits, Expert Rev Anti Infect Ther
Bui, Zhu, Hawkins, Cortez-Resendiz, Bellon, Vitamin D regulation of the immune system and its implications for COVID-19: a mini review, SAGE Open Med
Dissanayake, Silva, Sumanatilleke, De Silva, Gamage et al., Prognostic and therapeutic role of vitamin D in COVID-19: systematic review and meta-analysis, J Clin Endocrinol Metab
Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline, J Clin Endocrinol Metab
Huang, Wang, Li, Ren, Zhao et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet Lond Engl
Neves, Pott-Junior, De Sousa Santos, None, Clinical Nutrition ESPEN
Neves, Pott-Junior, De Sousa Santos, None, Clinical Nutrition ESPEN
Tay, Poh, Macary, Ng, The trinity of COVID-19: immunity, inflammation and intervention, Nat Rev Immunol
Tentolouris, Samakidou, Eleftheriadou, Tentolouris, Jude, The effect of vitamin D supplementation on mortality and Intensive Care Unit admission of COVID-19 patients. A systematic review, meta-analysis and meta-regression, Diabetes Metab Res Rev
Yisak, Ewunetei, Kefale, Mamuye, Teshome et al., Effects of vitamin D on COVID-19 infection and prognosis: a systematic review, Risk Manag Healthc Pol
{ 'indexed': {'date-parts': [[2022, 7, 21]], 'date-time': '2022-07-21T17:41:27Z', 'timestamp': 1658425287408},
'reference-count': 10,
'publisher': 'Elsevier BV',
'license': [ { 'start': { 'date-parts': [[2022, 8, 1]],
'date-time': '2022-08-01T00:00:00Z',
'timestamp': 1659312000000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'}],
'content-domain': { 'domain': [ 'clinicalkey.fr', 'clinicalkey.jp', 'clinicalkey.com.au', 'clinicalkey.es',
'clinicalkey.com', 'clinicalnutritionespen.com', 'elsevier.com',
'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2022, 8]]},
'DOI': '10.1016/j.clnesp.2022.05.027',
'type': 'journal-article',
'created': {'date-parts': [[2022, 6, 14]], 'date-time': '2022-06-14T17:19:41Z', 'timestamp': 1655227181000},
'page': '322-325',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 0,
'title': 'Vitamin D deficiency predicts 30-day hospital mortality of adults with COVID-19',
'prefix': '10.1016',
'volume': '50',
'author': [ { 'ORCID': 'http://orcid.org/0000-0001-6536-3249',
'authenticated-orcid': False,
'given': 'Fabio Fernandes',
'family': 'Neves',
'sequence': 'first',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-3126-2946',
'authenticated-orcid': False,
'given': 'Henrique',
'family': 'Pott-Junior',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0003-0366-0250',
'authenticated-orcid': False,
'given': 'Sigrid',
'family': 'de Sousa Santos',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0001-6385-7392',
'authenticated-orcid': False,
'given': 'Marcia Regina',
'family': 'Cominetti',
'sequence': 'additional',
'affiliation': []},
{ 'given': 'Caio Cesar',
'family': 'de Melo Freire',
'sequence': 'additional',
'affiliation': []},
{ 'given': 'Anderson Ferreira',
'family': 'da Cunha',
'sequence': 'additional',
'affiliation': []},
{ 'given': 'Alceu Afonso Jordão',
'family': 'Júnior',
'sequence': 'additional',
'affiliation': []}],
'member': '78',
'reference': [ { 'issue': '10223',
'key': '10.1016/j.clnesp.2022.05.027_bib1',
'doi-asserted-by': 'crossref',
'first-page': '497',
'DOI': '10.1016/S0140-6736(20)30183-5',
'article-title': 'Clinical features of patients infected with 2019 novel coronavirus in '
'Wuhan, China',
'volume': '395',
'author': 'Huang',
'year': '2020',
'journal-title': 'Lancet Lond Engl'},
{ 'issue': '6',
'key': '10.1016/j.clnesp.2022.05.027_bib2',
'doi-asserted-by': 'crossref',
'first-page': '363',
'DOI': '10.1038/s41577-020-0311-8',
'article-title': 'The trinity of COVID-19: immunity, inflammation and intervention',
'volume': '20',
'author': 'Tay',
'year': '2020',
'journal-title': 'Nat Rev Immunol'},
{ 'issue': '10',
'key': '10.1016/j.clnesp.2022.05.027_bib3',
'doi-asserted-by': 'crossref',
'first-page': '1245',
'DOI': '10.1080/14787210.2021.1905519',
'article-title': 'Vitamin D and immuno-pathology of COVID-19: many interactions but '
'uncertain therapeutic benefits',
'volume': '19',
'author': 'Banerjee',
'year': '2021',
'journal-title': 'Expert Rev Anti Infect Ther'},
{ 'issue': '10',
'key': '10.1016/j.clnesp.2022.05.027_bib4',
'doi-asserted-by': 'crossref',
'first-page': '1373',
'DOI': '10.1016/j.jiph.2020.06.021',
'article-title': 'Role of vitamin D in preventing of COVID-19 infection, progression and '
'severity',
'volume': '13',
'author': 'Ali',
'year': '2020',
'journal-title': 'J\xa0Infect Public Health'},
{ 'key': '10.1016/j.clnesp.2022.05.027_bib5',
'doi-asserted-by': 'crossref',
'DOI': '10.1177/20503121211014073',
'article-title': 'Vitamin D regulation of the immune system and its implications for '
'COVID-19: a mini review',
'volume': '9',
'author': 'Bui',
'year': '2021',
'journal-title': 'SAGE Open Med'},
{ 'key': '10.1016/j.clnesp.2022.05.027_bib6',
'doi-asserted-by': 'crossref',
'first-page': '31',
'DOI': '10.2147/RMHP.S291584',
'article-title': 'Effects of vitamin D on COVID-19 infection and prognosis: a systematic '
'review',
'volume': '14',
'author': 'Yisak',
'year': '2021',
'journal-title': 'Risk Manag Healthc Pol'},
{ 'key': '10.1016/j.clnesp.2022.05.027_bib7',
'article-title': 'Low serum 25-hydroxyvitamin D (vitamin D) level is associated with '
'susceptibility to COVID-19, severity, and mortality: a systematic '
'review and meta-analysis',
'volume': '8',
'author': 'Akbar',
'year': '2021',
'journal-title': 'Front Nutr'},
{ 'key': '10.1016/j.clnesp.2022.05.027_bib8',
'first-page': 'dgab892',
'article-title': 'Prognostic and therapeutic role of vitamin D in COVID-19: systematic '
'review and meta-analysis',
'author': 'Dissanayake',
'year': '2021',
'journal-title': 'J\xa0Clin Endocrinol Metab'},
{ 'issue': '7',
'key': '10.1016/j.clnesp.2022.05.027_bib9',
'doi-asserted-by': 'crossref',
'first-page': '1911',
'DOI': '10.1210/jc.2011-0385',
'article-title': 'Evaluation, treatment, and prevention of vitamin D deficiency: an '
'Endocrine Society clinical practice guideline',
'volume': '96',
'author': 'Holick',
'year': '2011',
'journal-title': 'J\xa0Clin Endocrinol Metab'},
{ 'key': '10.1016/j.clnesp.2022.05.027_bib10',
'first-page': 'e3517',
'article-title': 'The effect of vitamin D supplementation on mortality and Intensive Care '
'Unit admission of COVID-19 patients. A systematic review, meta-analysis '
'and meta-regression',
'author': 'Tentolouris',
'year': '2021',
'journal-title': 'Diabetes Metab Res Rev'}],
'container-title': 'Clinical Nutrition ESPEN',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://api.elsevier.com/content/article/PII:S2405457722002935?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S2405457722002935?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'}],
'deposited': { 'date-parts': [[2022, 7, 21]],
'date-time': '2022-07-21T17:17:35Z',
'timestamp': 1658423855000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S2405457722002935'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 8]]},
'references-count': 10,
'alternative-id': ['S2405457722002935'],
'URL': 'http://dx.doi.org/10.1016/j.clnesp.2022.05.027',
'relation': {},
'ISSN': ['2405-4577'],
'subject': ['Nutrition and Dietetics', 'Endocrinology, Diabetes and Metabolism'],
'container-title-short': 'Clinical Nutrition ESPEN',
'published': {'date-parts': [[2022, 8]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Vitamin D deficiency predicts 30-day hospital mortality of adults with COVID-19',
'name': 'articletitle',
'label': 'Article Title'},
{'value': 'Clinical Nutrition ESPEN', 'name': 'journaltitle', 'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1016/j.clnesp.2022.05.027',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': '© 2022 European Society for Clinical Nutrition and Metabolism. Published by '
'Elsevier Ltd. All rights reserved.',
'name': 'copyright',
'label': 'Copyright'}]}
