Vitamin D, vitamin D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients.


Journal

The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027

Informations de publication

Date de publication:
01 05 2022
Historique:
received: 24 09 2021
accepted: 27 01 2022
pubmed: 2 2 2022
medline: 10 5 2022
entrez: 1 2 2022
Statut: ppublish

Résumé

Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed. We aimed to examine the relationship between vitamin D status and mortality from COVID-19. In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression. There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality. Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).

Sections du résumé

BACKGROUND
Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed.
OBJECTIVES
We aimed to examine the relationship between vitamin D status and mortality from COVID-19.
METHODS
In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression.
RESULTS
There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality.
CONCLUSIONS
Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).

Identifiants

pubmed: 35102371
pii: S0002-9165(22)00259-3
doi: 10.1093/ajcn/nqac027
pmc: PMC8903333
doi:

Substances chimiques

Albumins 0
Vitamin D-Binding Protein 0
Vitamins 0
Vitamin D 1406-16-2

Types de publication

Journal Article Observational Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1367-1377

Informations de copyright

© Crown copyright 2022.

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Auteurs

Sreedhar Subramanian (S)

Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

Jonathan M Rhodes (JM)

Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

Joseph M Taylor (JM)

Department of Clinical Chemistry, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Anna M Milan (AM)

Department of Clinical Chemistry, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Steven Lane (S)

Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

Martin Hewison (M)

Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom.

Rene F Chun (RF)

Department of Orthopaedic Surgery, University of California, Los Angeles, CA, USA.

Andrea Jorgensen (A)

Department of Health Data Science, University of Liverpool, Liverpool, United Kingdom.

Paul Richardson (P)

Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Darshan Nitchingham (D)

Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Joseph Aslan (J)

Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Maya Shah (M)

Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Coonoor R Chandrasekar (CR)

Department of Orthopaedic Surgery, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Amanda Wood (A)

Department of Clinical Pharmacology, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Mike Beadsworth (M)

Tropical and Infectious Diseases Unit, Liverpool University Hospital Foundation NHS Trust, Liverpool, United Kingdom.

Munir Pirmohamed (M)

Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.

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