Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study
Emma A Hurst, Richard J Mellanby, Ian Handel, David M Griffith, Adriano G Rossi, Timothy S Walsh, Manu Shankar-Hari, Jake Dunning, Natalie Z Homer, Scott G Denham, Kerri Devine, Paul A Holloway, Shona C Moore, Ryan S Thwaites, Romit J Samanta, Charlotte Summers, Hayley E Hardwick, Wilna Oosthuyzen, Lance Turtle, Malcolm G Semple, Peter J M Openshaw, J Kenneth Baillie, Dr Clark D Russell
BMJ Open, doi:10.1136/bmjopen-2021-055435
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 COVID-19 samples. 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 mediators. 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 causal in progression to severe disease, and investigation of longer-term bone health outcomes.
Ethics approval Ethical approval for the ISARIC/WHO CCP-UK study (COVID- 19) was given by the South Central Oxford C Research Ethics Committee in England (13/SC/0149), the Scotland A Research Ethics Committee (20/SS/0028), and the WHO Ethics Review Committee (RPC571 and RPC572, 25 April 2013). Ethical approval for the MOSAIC study (influenza A) was given by the NHS National Research Ethics Service, Outer West London Research Ethics Committee (09/ H0709/52, 09/MRE00/67). Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available upon reasonable request. Data generated by the ISARIC4C consortium is available for collaborative analysis projects through an independent data and materials access committee at isaric4c. net/ sample_ access. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and..
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'abstract': '<jats:sec><jats:title>Objectives</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Cross-sectional '
'study.</jats:p></jats:sec><jats:sec><jats:title>Setting and '
'participants</jats:title><jats:p>Plasma was obtained from 295 hospitalised people with '
'COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium '
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'with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the '
'2009–2010\u2009H1N1 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 COVID-19 '
'samples.</jats:p></jats:sec><jats:sec><jats:title>Outcome '
'measures</jats:title><jats:p>Receipt of invasive mechanical ventilation (IMV) and in-hospital '
'mortality.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Vitamin D '
'insufficiency (total 25(OH)D 25–50\u2009nmol/L) and deficiency (<25\u2009nmol/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\u2009nmol/L '
'(p<0.0001)\u2009and 22.9 vs 31.1\u2009nmol/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 '
'mediators.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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 causal in progression to severe '
'disease, and investigation of longer-term bone health outcomes.</jats:p></jats:sec>',
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