BMJ Open (Oct 2021)

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

  • David Price,
  • Mark Roberts,
  • Andrew Walden,
  • Jason Kendall,
  • Clark D Russell,
  • Natalie Pattison,
  • Daniel B Hawcutt,
  • George Koshy,
  • Adam Finn,
  • Ellen G Murphy,
  • Ewen M Harrison,
  • Maria Zambon,
  • Michael Murphy,
  • Tom Solomon,
  • Carrol Gamble,
  • Laura Marsh,
  • Nicholas Barrett,
  • Nigel Chee,
  • Paul Dark,
  • Clive Graham,
  • Andrew Law,
  • Richard J Mellanby,
  • Gail Carson,
  • Jake Dunning,
  • Laura Merson,
  • Ingeborg Welters,
  • Stephen R Knight,
  • Thomas M Drake,
  • Tamas Szakmany,
  • Robert Thompson,
  • Richard Smith,
  • Ian Handel,
  • Kenneth A McLean,
  • Sam Douthwaite,
  • David Baxter,
  • Patrick Lillie,
  • Dougal Atkinson,
  • Chris Dunn,
  • James Moon,
  • Paul Klenerman,
  • Catherine Hartley,
  • Mandeep Phull,
  • Pieter Bothma,
  • Craig Morris,
  • Adam Wolverson,
  • Ana Alegria,
  • Lawrence Wilson,
  • Susan Jain,
  • James Limb,
  • Vanessa Linnett,
  • Chris Dawson,
  • Jason Cupitt,
  • Sam Waddy,
  • Guy Rousseau,
  • Andrew Burtenshaw,
  • Devender Roberts,
  • Samreen Ijaz,
  • Mark Nelson,
  • Anthony Evans,
  • Meera Chand,
  • Wei Shen Lim,
  • Catherine A Shaw,
  • Cameron J Fairfield,
  • Timothy S Walsh,
  • Anil Hormis,
  • Peter W Horby,
  • Marlies Ostermann,
  • Tim Reynolds,
  • Mark Lyttle,
  • Bryan Yates,
  • Chloe Donohue,
  • Anil Sharma,
  • Jenny Child,
  • Elaine Hardy,
  • Julian A Hiscox,
  • Debby Bogaert,
  • Richard Stewart,
  • Martin Williams,
  • Adriano G Rossi,
  • Catherine Cosgrove,
  • David M Griffith,
  • William Greenhalf,
  • Thapas Nagarajan,
  • Saye Khoo,
  • Annemarie B Docherty,
  • Christopher A Green,
  • Hayley E Hardwick,
  • Riinu Pius,
  • Lisa Norman,
  • Louise Sigfrid,
  • Sophie Halpin,
  • Clare Jackson,
  • J Kenneth Baillie,
  • Malcolm G Semple,
  • Manu Shankar-Hari,
  • Carlo Palmieri,
  • Lance Turtle,
  • Stuart Hartshorn,
  • Rishi K Gupta,
  • Tom Fletcher,
  • Michelle Girvan,
  • Peter J M Openshaw,
  • Beatrice Alex,
  • Benjamin Bach,
  • Wendy S Barclay,
  • Graham S Cooke,
  • Alexander J Mentzer,
  • Alison M Meynert,
  • Mahdad Noursadeghi,
  • Shona C Moore,
  • Massimo Palmarini,
  • William A Paxton,
  • Georgios Pollakis,
  • Nicholas Price,
  • Andrew Rambaut,
  • David L Robertson,
  • Vanessa Sancho-Shimizu,
  • Janet T Scott,
  • Shiranee Sriskandan,
  • David Stuart,
  • Charlotte Summers,
  • Richard S Tedder,
  • Emma C Thomson,
  • Ryan S Thwaites,
  • Lance C W Turtle,
  • Hayley Hardwick,
  • Wilna Oosthuyzen,
  • Fiona Griffiths,
  • Derek Murphy,
  • Jo Dalton,
  • Egle Saviciute,
  • Stephanie Roberts,
  • Janet Harrison,
  • Marie Connor,
  • Gary Leeming,
  • Ross Hendry,
  • Victoria Shaw,
  • Sarah McDonald,
  • Katie A Ahmed,
  • Jane A Armstrong,
  • Milton Ashworth,
  • Innocent G Asiimwe,
  • Siddharth Bakshi,
  • Samantha L Barlow,
  • Laura Booth,
  • Benjamin Brennan,
  • Katie Bullock,
  • Jordan J Clark,
  • Emily A Clarke,
  • Sarah Cole,
  • Louise Cooper,
  • Helen Cox,
  • Christopher Davis,
  • Oslem Dincarslan,
  • Philip Dyer,
  • Angela Elliott,
  • Lewis W S Fisher,
  • Terry Foster,
  • Isabel Garcia-Dorival,
  • Philip Gunning,
  • Rebecca L Jensen,
  • Christopher B Jones,
  • Trevor R Jones,
  • Shadia Khandaker,
  • Katharine King,
  • Robyn T Kiy,
  • Chrysa Koukorava,
  • Annette Lake,
  • Suzannah Lant,
  • Diane Latawiec,
  • Daniella Lefteri,
  • Lauren Lett,
  • Lucia A Livoti,
  • Maria Mancini,
  • Laurence McEvoy,
  • John McLauchlan,
  • Soeren Metelmann,
  • Nahida S Miah,
  • Joanna Middleton,
  • Joyce Mitchell,
  • Rebekah Penrice-Randal,
  • Jack Pilgrim,
  • Tessa Prince,
  • Debby Sales,
  • Victoria E Shaw,
  • Rebecca K Shears,
  • Benjamin Small,
  • Krishanthi S Subramaniam,
  • Agnieska Szemiel,
  • Aislynn Taggart,
  • Jordan Thomas,
  • Erwan Trochu,
  • Eve Wilcock,
  • Kayode Adeniji,
  • Daniel Agranoff,
  • Ken Agwuh,
  • Dhiraj Ail,
  • Brian Angus,
  • Abdul Ashish,
  • Shahedal Bari,
  • Gavin Barlow,
  • Stella Barnass,
  • Michael Beadsworth,
  • Jolanta Bernatoniene,
  • John Berridge,
  • Nicola Best,
  • Robin Brittain-Long,
  • Naomi Bulteel,
  • Tom Burden,
  • Vikki Caruth,
  • David Chadwick,
  • Duncan Chambler,
  • Srikanth Chukkambotla,
  • Tom Clark,
  • Paul Collini,
  • Maria-Teresa Cutino-Moguel,
  • Samir Dervisevic,
  • Phil Donnison,
  • Ingrid DuRand,
  • Ahilanadan Dushianthan,
  • Tristan Dyer,
  • Cariad Evans,
  • Chi Eziefula,
  • Duncan Fullerton,
  • Sanjeev Garg,
  • Atul Garg,
  • Jo Godden,
  • Arthur Goldsmith,
  • Daniel Harvey,
  • Peter Havalda,
  • Maria Hobrok,
  • Luke Hodgson,
  • Michael Jacobs,
  • Paul Jennings,
  • Agilan Kaliappan,
  • Vidya Kasipandian,
  • Stephen Kegg,
  • Michael Kelsey,
  • Caroline Kerrison,
  • Ian Kerslake,
  • Oliver Koch,
  • Gouri Koduri,
  • Shondipon Laha,
  • Susan Larkin,
  • Tamas Leiner,
  • Jeff Little,
  • Michael MacMahon,
  • Emily MacNaughton,
  • Ravish Mankregod,
  • Huw Masson,
  • Elijah Matovu,
  • Katherine McCullough,
  • Ruth McEwen,
  • Manjula Meda,
  • Gary Mills,
  • Jane Minton,
  • Mariyam Mirfenderesky,
  • Kavya Mohandas,
  • Quen Mok,
  • Elinoor Moore,
  • Patrick Morgan,
  • Katherine Mortimore,
  • Samuel Moses,
  • Mbiye Mpenge,
  • Rohinton Mulla,
  • Megan Nagel,
  • Igor Otahal,
  • Mark Pais,
  • Selva Panchatsharam,
  • Hassan Paraiso,
  • Brij Patel,
  • Justin Pepperell,
  • Mark Peters,
  • Stefania Pintus,
  • Jagtur Singh Pooni,
  • Frank Post,
  • Rachel Prout,
  • Nikolas Rae,
  • Henrik Reschreiter,
  • Neil Richardson,
  • Alistair Rose,
  • Brendan Ryan,
  • Taranprit Saluja,
  • Aarti Shah,
  • Prad Shanmuga,
  • Anna Shawcross,
  • Jeremy Sizer,
  • Catherine Snelson,
  • Nick Spittle,
  • Nikki Staines,
  • Tom Stambach,
  • Pradeep Subudhi,
  • Kate Tatham,
  • Jo Thomas,
  • Chris Thompson,
  • Ascanio Tridente,
  • Darell Tupper-Carey,
  • Mary Twagira,
  • Andrew Ustianowski,
  • Nick Vallotton,
  • Lisa Vincent-Smith,
  • Shico Visuvanathan,
  • Alan Vuylsteke,
  • Rachel Wake,
  • Tony Whitehouse,
  • Paul Whittaker,
  • Ashley Whittington,
  • Meme Wijesinghe,
  • Stephen Winchester,
  • Martin Wiselka,
  • Andrew Workman,
  • Peter Young,
  • James Scott-Brown,
  • Will Reynolds,
  • Jolanta Tanianis-Hughes,
  • Chrisopher Fegan,
  • Danai Papakonstantinou,
  • Effrossyni Gkrania-Klotsas,
  • Kerri Devine,
  • Daniel G Wootton,
  • Padmasayee Papineni,
  • Benjamin W A Catterall,
  • Lara Lavelle-Langham,
  • Emily Cass,
  • Alejandra Doce Carracedo,
  • Lisa Flaherty,
  • Nicole Maziere,
  • Hannah Massey,
  • Anthony Holmes,
  • Nicola Carlucci,
  • Matthew K O'Shea,
  • Libby van Tonder,
  • Emma A Hurst,
  • Natalie Z Homer,
  • Scott G Denham,
  • Paul A Holloway,
  • Romit J Samanta,
  • J Kenneth Baillie,
  • Ana da Silva Filipe,
  • Thushan de Silva,
  • A A Roger Thompson,
  • Ruth Lyons,
  • Murray Wham,
  • Sara Clohisey,
  • Sara McDonald,
  • Seán Keating,
  • Lorna Finch,
  • P Matthew Ridley,
  • J Eunice Zhang,
  • Lee Murphy,
  • Nicola Wrobel,
  • Sarah McCafferty,
  • Kirstie Morrice,
  • Alan MacLean,
  • Erin L Aldera,
  • Sneha Basude,
  • Steven Laird,
  • Antonia Ying Wai Ho

DOI
https://doi.org/10.1136/bmjopen-2021-055435
Journal volume & issue
Vol. 11, no. 10

Abstract

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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.