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 journalArticlepeer-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 languageEnglish
JournalBMJ Open
Early online date22 Oct 2021
Publication statusE-pub ahead of print - 22 Oct 2021


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