Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study
et al., BMJ Open,
Analysis of 259 hospitalized COVID-19 patients in the UK, showing a majority of patients had vitamin D deficiency/insufficiency, which was associated with poor outcomes. Both free and total 25(OH)D were analyzed with consistent results. ISRCTN66726260.
risk of death, 68.4% lower, RR 0.32, p = 0.005, high D levels 68, low D levels 191, odds ratio converted to relative risk, >50nmol/l, multivariable, Supplementary Table 2, control prevalance approximated with overall prevalence.
risk of mechanical ventilation, 66.0% lower, RR 0.34, p = 0.004, high D levels 6 of 68 (8.8%), low D levels 61 of 191 (31.9%), NNT 4.3, odds ratio converted to relative risk, >50nmol/l, multivariable, Supplementary Table 2.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hurst et al., 22 Oct 2021, prospective, United Kingdom, peer-reviewed, 23 authors.
Abstract: Open access
Emma A Hurst,1,2 Richard J Mellanby,1 Ian Handel,1 David M Griffith ,3
Adriano G Rossi,4 Timothy S Walsh,4,5 Manu Shankar-Hari,6,7 Jake Dunning,8
Natalie Z Homer,2 Scott G Denham,2 Kerri Devine,2 Paul A Holloway,9
Shona C Moore,10 Ryan S Thwaites,11 Romit J Samanta,12
Charlotte Summers ,12 Hayley E Hardwick,10 Wilna Oosthuyzen,13
Lance Turtle,10,14 Malcolm G Semple,10,15 Peter J M Openshaw,11
J Kenneth Baillie,5,13 Clark D Russell ,4,13 ISARIC4C Investigators
To cite: Hurst EA, Mellanby RJ,
Handel I, et al. Vitamin D
insufficiency in COVID-19
and influenza A, and critical
illness survivors: a cross-
sectional study. BMJ Open
►► Prepublication history and
additional supplemental material
for this paper are available
online. To view these files,
please visit the journal online
Received 13 July 2021
Accepted 30 September 2021
© Author(s) (or their
employer(s)) 2021. Re-use
permitted under CC BY.
Published by BMJ.
For numbered affiliations see
end of article.
Dr Clark D Russell;
Objectives The steroid hormone vitamin D has roles
in immunomodulation and bone health. Insufficiency is
associated with susceptibility to respiratory infections. We
report 25-hydroxy vitamin D (25(OH)D) measurements in
hospitalised people with COVID-19 and influenza A and
in survivors of critical illness to test the hypotheses that
vitamin D insufficiency scales with illness severity and
persists in survivors.
Design Cross-sectional study.
Setting and participants Plasma was obtained from
295 hospitalised people with COVID-19 (International
Severe Acute Respiratory and emerging Infections
Consortium (ISARIC)/WHO Clinical Characterization
Protocol for Severe Emerging Infections UK study), 93
with influenza A (Mechanisms of Severe Acute Influenza
Consortium (MOSAIC) study, during the 2009–2010 H1N1
pandemic) and 139 survivors of non-selected critical
illness (prior to the COVID-19 pandemic). Total 25(OH)D
was measured by liquid chromatography-tandem mass
spectrometry. Free 25(OH)D was measured by ELISA in
Outcome measures Receipt of invasive mechanical
ventilation (IMV) and in-hospital mortality.
Results Vitamin D insufficiency (total 25(OH)D 25–
50 nmol/L) and deficiency (<25 nmol/L) were prevalent in
COVID-19 (29.3% and 44.4%, respectively), influenza A
(47.3% and 37.6%) and critical illness survivors (30.2%
and 56.8%). In COVID-19 and influenza A, total 25(OH)
D measured early in illness was lower in patients who
received IMV (19.6 vs 31.9 nmol/L (p<0.0001) and 22.9
vs 31.1 nmol/L (p=0.0009), respectively). In COVID-19,
biologically active free 25(OH)D correlated with total
25(OH)D and was lower in patients who received IMV, but
was not associated with selected circulating inflammatory
Conclusions Vitamin D deficiency/insufficiency was
present in majority of hospitalised patients with COVID-19
or influenza A and correlated with severity and persisted
in critical illness survivors at concentrations expected to
disrupt bone metabolism. These findings support early
supplementation trials to determine if insufficiency is
Strengths and limitations of this study
►► Liquid chromatography-tandem mass spectrometry
was used to quantify 25-hydroxy vitamin D (25(OH)
D) in plasma samples from well-characterised..
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