Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Emma Hurst; Richard Mellanby; Ian Handel; David M Griffith; Adriano G Rossi; Timothy S. Walsh; Manu Shankar-Hari; Jake Dunning; Natalie Z M Homer; Scott Denham; Kerri Devine; A Holloway; Shona C Moore; Ryan S  Thwaites; Romit J  Samanta; Charlotte Summers; Hayley E Hardwick; Wilna Oosthuyzen; Lance  Turtle; Malcolm G Semple; Peter Openshaw; Kenneth Baillie; Clark D Russell

doi:10.1136/bmjopen-2021-055435

Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Emma Hurst, Richard Mellanby, Ian Handel, David M Griffith, Adriano G Rossi, Timothy S. Walsh, Manu Shankar-Hari, Jake Dunning, Natalie Z M Homer, Scott Denham, Kerri Devine, A Holloway, Shona C Moore, Ryan S Thwaites, Romit J Samanta, Charlotte Summers, Hayley E Hardwick, Wilna Oosthuyzen, Lance Turtle, Malcolm G SemplePeter Openshaw, Kenneth Baillie, Clark D Russell^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Objectives: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25(OH)D measurements in hospitalised people with COVID-19 and influenza A, and 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 (ISARIC/WHO CCP-UK study), 93 with influenza A (MOSAIC study, during the 2009-10 H1N1 pandemic), and 139 survivors of non-selected critical illness (prior to 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 (<25nmol/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, was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators.
Conclusions: Vitamin D deficiency/insufficiency was present in the majority of hospitalised patients with COVID-19 or influenza A, 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.

Original language	English
Journal	BMJ Open
Early online date	22 Oct 2021
DOIs	https://doi.org/10.1136/bmjopen-2021-055435
Publication status	E-pub ahead of print - 22 Oct 2021

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Natalie Homer (Manager), Scott Denham (Other) & Jo Simpson (Other)
Centre for Cardiovascular Science
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Hurst, E., Mellanby, R., Handel, I., Griffith, D. M., Rossi, A. G., Walsh, T. S., Shankar-Hari, M., Dunning, J., Homer, N. Z. M., Denham, S., Devine, K., Holloway, A., Moore, S. C., Thwaites, R. S., Samanta, R. J., Summers, C., Hardwick, H. E., Oosthuyzen, W., Turtle, L., ... Russell, C. D. (2021). Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study. BMJ Open. Advance online publication. https://doi.org/10.1136/bmjopen-2021-055435

@article{1099cc2a1d58438083ae7edbd54befeb,

title = "Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study",

abstract = "Objectives: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25(OH)D measurements in hospitalised people with COVID-19 and influenza A, and survivors of critical illness, to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.Design: Cross-sectional studySetting and Participants: Plasma was obtained from 295 hospitalised people with COVID-19 (ISARIC/WHO CCP-UK study), 93 with influenza A (MOSAIC study, during the 2009-10 H1N1 pandemic), and 139 survivors of non-selected critical illness (prior to 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 (<25nmol/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, was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators.Conclusions: Vitamin D deficiency/insufficiency was present in the majority of hospitalised patients with COVID-19 or influenza A, 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.",

author = "Emma Hurst and Richard Mellanby and Ian Handel and Griffith, {David M} and Rossi, {Adriano G} and Walsh, {Timothy S.} and Manu Shankar-Hari and Jake Dunning and Homer, {Natalie Z M} and Scott Denham and Kerri Devine and A Holloway and Moore, {Shona C} and Thwaites, {Ryan S} and Samanta, {Romit J} and Charlotte Summers and Hardwick, {Hayley E} and Wilna Oosthuyzen and Lance Turtle and Semple, {Malcolm G} and Peter Openshaw and Kenneth Baillie and Russell, {Clark D}",

year = "2021",

month = oct,

day = "22",

doi = "10.1136/bmjopen-2021-055435",

language = "English",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

}

Hurst, E, Mellanby, R, Handel, I, Griffith, DM , Rossi, AG , Walsh, TS , Shankar-Hari, M, Dunning, J, Homer, NZM , Denham, S, Devine, K, Holloway, A, Moore, SC, Thwaites, RS, Samanta, RJ, Summers, C, Hardwick, HE, Oosthuyzen, W, Turtle, L, Semple, MG, Openshaw, P, Baillie, K & Russell, CD 2021, 'Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study', BMJ Open. https://doi.org/10.1136/bmjopen-2021-055435

TY - JOUR

T1 - Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

AU - Hurst, Emma

AU - Mellanby, Richard

AU - Handel, Ian

AU - Griffith, David M

AU - Rossi, Adriano G

AU - Walsh, Timothy S.

AU - Shankar-Hari, Manu

AU - Dunning, Jake

AU - Homer, Natalie Z M

AU - Denham, Scott

AU - Devine, Kerri

AU - Holloway, A

AU - Moore, Shona C

AU - Thwaites, Ryan S

AU - Samanta, Romit J

AU - Summers, Charlotte

AU - Hardwick, Hayley E

AU - Oosthuyzen, Wilna

AU - Turtle, Lance

AU - Semple, Malcolm G

AU - Openshaw, Peter

AU - Baillie, Kenneth

AU - Russell, Clark D

PY - 2021/10/22

Y1 - 2021/10/22

N2 - Objectives: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25(OH)D measurements in hospitalised people with COVID-19 and influenza A, and survivors of critical illness, to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.Design: Cross-sectional studySetting and Participants: Plasma was obtained from 295 hospitalised people with COVID-19 (ISARIC/WHO CCP-UK study), 93 with influenza A (MOSAIC study, during the 2009-10 H1N1 pandemic), and 139 survivors of non-selected critical illness (prior to 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 (<25nmol/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, was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators.Conclusions: Vitamin D deficiency/insufficiency was present in the majority of hospitalised patients with COVID-19 or influenza A, 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.

AB - Objectives: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25(OH)D measurements in hospitalised people with COVID-19 and influenza A, and survivors of critical illness, to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors.Design: Cross-sectional studySetting and Participants: Plasma was obtained from 295 hospitalised people with COVID-19 (ISARIC/WHO CCP-UK study), 93 with influenza A (MOSAIC study, during the 2009-10 H1N1 pandemic), and 139 survivors of non-selected critical illness (prior to 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 (<25nmol/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, was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators.Conclusions: Vitamin D deficiency/insufficiency was present in the majority of hospitalised patients with COVID-19 or influenza A, 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.

U2 - 10.1136/bmjopen-2021-055435

DO - 10.1136/bmjopen-2021-055435

M3 - Article

SN - 2044-6055

JO - BMJ Open

JF - BMJ Open

ER -

Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

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