Abstract: Vitamin D, D-binding protein, free vitamin D and COVID-19
mortality in hospitalized patients.
Short title: Vitamin D and COVID-19 mortality
PT
Martin Hewison5, Rene F Chun6, Andrea Jorgensen7, Paul Richardson1, Darshan Nitchingham1,
RI
Joseph Aslan1, Maya Shah1, Coonoor R Chandrasekar8, Amanda Wood9, Mike Beadsworth10,
Department of Gastroenterology, Liverpool University Hospital Foundation NHS Trust, Liverpool,
N
U
1
SC
Munir Pirmohamed11
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University
M
2
A
UK
3
IT
ED
of Liverpool
Department of Clinical Chemistry, Liverpool University Hospital Foundation NHS Trust,
Liverpool, UK
Department of Biostatistics, Institute of Translational Medicine, University of Liverpool,
ED
4
N
Liverpool, UK
Institute of Metabolism and Systems Research, University of Birmingham
6
Department of Orthopaedic Surgery, University of California, Los Angeles
7
Department of Health Data Science, University of Liverpool, Liverpool, UK
8
Department of Orthopaedic Surgery, Liverpool University Hospital Foundation NHS Trust,
IN
A
L
U
5
Department of Clinical Pharmacology, Liverpool University Hospital Foundation NHS Trust,
O
RI
9
G
Liverpool, UK
Liverpool, UK
© Crown copyright 2022. This article contains public sector information licensed under the Open Government Licence v3.0
(http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/).
Sreedhar Subramanian1, 2 ¶, Jonathan M Rhodes2, , Joseph M Taylor3, Anna M Milan3, Steven Lane4,
10
Tropical and Infectious Diseases Unit, Liverpool University Hospital Foundation NHS Trust,
Liverpool, UK
11
Department of Molecular and Clinical Pharmacology, University of Liverpool
¶
Corresponding author:
Consultant Gastroenterologist and Honorary Senior Lecturer
PT
Department of Gastroenterology
RI
Liverpool University Hospital Foundation NHS Trust and University of Liverpool
SC
Prescot Street
Liverpool L7 8XP, UK
N
U
Email: sreedhar.subramanian@liverpoolft.nhs.uk
A
Acknowledgements: None
M
Registration: The study protocol was approved by the London-Surrey Research Ethics Committee
IT
ED
(20/HRA/2282).
Funding Source: This research was funded by an internal departmental grant from Liverpool
ED
University Hospitals NHS Foundation Trust. The funders had no input into study design or final
Guarantor of the article
A
L
U
Dr Sreedhar Subramanian
N
analysis.
IN
Author contributions: SS, JR, MP, JT and AM were involved in study design and initial drafting
G
of the manuscript. SL was involved in data analysis. All authors revised and approved the final
O
RI
version of the manuscript.
Sreedhar Subramanian, MD, FRCP
Conflict of interest: JMR with the University of Liverpool and Provexis UK, holds a patent for
use of a soluble fibre preparation as maintenance therapy for Crohn’s disease plus a patent for its
use in antibiotic-associated diarrhoea. Patent also held with the University of Liverpool and others
in relation to use of modified heparins in cancer therapy. SS has received speaker fees from MSD,
Actavis, Abbvie, Dr Falk pharmaceuticals, Janssen, Takeda, Boehringer-Ingelheim, Shire and
Abbvie, Dr Falk..
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>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 25(OH)D status hard to interpret. Because of this, measurement of unbound “free” and '
'albumin-bound “bioavailable” 25(OH) D has been proposed.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Objective</jats:title>\n'
' <jats:p>We aimed to examine the relationship between vitamin D status and '
'mortality from COVID-19.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>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 co-morbidities 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.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Findings</jats:title>\n'
' <jats:p>Four hundred and seventy-two patients with COVID-19 were included, '
'of whom 112 (23.7%) died within 28 days. Non-survivors were older (mean age 73, [range '
'34-98]) than survivors (65, [19-95]; P = 0.003) and more likely male (67%; P = 0.02). The '
'frequency of vitamin D deficiency (25(OH)D &lt;50nmol/L) was similar between '
'non-survivors (71/112 [63.4%]) and survivors (204/360 [56.7%]; P = 0.15) but, after '
'adjustment for age, sex and co-morbidities, increased odds for mortality were present in '
'those with severe deficiency (25(OH)D &lt;25nmol/L), OR 2.37 (95% CI 1.17, 4.78), or high '
'25(OH)D (≥100nmol/L), OR 4.65 (95% CI 1.51, 14.34) compared with 25(OH)D 50-74 nmol/L '
'(reference). Serum DBP levels were not associated with mortality after adjustment for '
'25(OH)D, age, sex and co-morbidities. Neither free nor bioavailable 25(OH)D were associated '
'with mortality.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusion</jats:title>\n'
' <jats:p>: Vitamin D deficiency as commonly defined by serum 25 (OH)D levels '
'(&lt;50nmol/L) is not associated with increased mortality from COVID-19 but extreme low '
'(&lt;25nmol/L) and high (&gt;100nmol/L) levels may be associated with risk. Neither '
'free nor bioavailable 25(OH) D associate with risk.</jats:p>\n'
' </jats:sec>',
'DOI': '10.1093/ajcn/nqac027',
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'created': {'date-parts': [[2022, 1, 27]], 'date-time': '2022-01-27T20:11:33Z', 'timestamp': 1643314293000},
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