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Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study
Copyright policy ) Natalie Pattison; Richard J Mellanby; Ian Handel; Timothy S Walsh; Marlies Ostermann; Mark Lyttle; Adriano G Rossi; +44 Authors
Natalie Pattison; Richard J Mellanby; Ian Handel; Timothy S Walsh; Marlies Ostermann; Mark Lyttle; Adriano G Rossi; David M Griffith; Manu Shankar-Hari; Carlo Palmieri; Lance Turtle; Alexander J Mentzer; Lewis W S Fisher; James Scott-Brown; 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; Emma A Hurst; Natalie Z Homer; Scott G Denham; Paul A Holloway; Romit J Samanta; Thushan de Silva; A A Roger Thompson; Ruth Lyons; Murray Wham; Sara Clohisey; Sara McDonald; Seán Keating; Lorna Finch; Lee Murphy; Nicola Wrobel; Sarah McCafferty; Kirstie Morrice; Alan MacLean; Erin L Aldera; Sneha Basude; Steven Laird; Antonia Ying Wai Ho;
Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study
ObjectivesThe 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.DesignCross-sectional study.Setting and participantsPlasma 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 measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin 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.ConclusionsVitamin 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.
United Kingdom
- Imperial College London United Kingdom
- University of Edinburgh United Kingdom
- University of Oxford United Kingdom
- St Thomas' Hospital United Kingdom
- King's College London United Kingdom
Microsoft Academic Graph classification: Cross-sectional study medicine.medical_treatment Bone remodeling Pandemic Medicine Respiratory system medicine.medical_specialty vitamin D deficiency Internal medicine Vitamin D and neurology Mechanical ventilation business.industry medicine.disease Steroid hormone business
2474, immunology, Influenza A Virus, H1N1 Subtype, INFECTION, 1506, Survivors, Vitamin D, 1706, R, General Medicine, Infectious Diseases, Medicine, AUTOPHAGY, Vitamin D Deficiency/complications, Life Sciences & Biomedicine, HIGH-DOSE VITAMIN-D-3, Influenza, Human/complications, intensive & critical care, D SUPPLEMENTATION, Critical Illness, 1117 Public Health and Health Services, D DEFICIENCY, respiratory infections, Medicine, General & Internal, General & Internal Medicine, Influenza, Human, Humans, ISARIC4C Investigators, Pandemics, Science & Technology, SARS-CoV-2, COVID-19, 1103 Clinical Sciences, Vitamin D Deficiency, Cross-Sectional Studies, 1199 Other Medical and Health Sciences
2474, immunology, Influenza A Virus, H1N1 Subtype, INFECTION, 1506, Survivors, Vitamin D, 1706, R, General Medicine, Infectious Diseases, Medicine, AUTOPHAGY, Vitamin D Deficiency/complications, Life Sciences & Biomedicine, HIGH-DOSE VITAMIN-D-3, Influenza, Human/complications, intensive & critical care, D SUPPLEMENTATION, Critical Illness, 1117 Public Health and Health Services, D DEFICIENCY, respiratory infections, Medicine, General & Internal, General & Internal Medicine, Influenza, Human, Humans, ISARIC4C Investigators, Pandemics, Science & Technology, SARS-CoV-2, COVID-19, 1103 Clinical Sciences, Vitamin D Deficiency, Cross-Sectional Studies, 1199 Other Medical and Health Sciences
Microsoft Academic Graph classification: Cross-sectional study medicine.medical_treatment Bone remodeling Pandemic Medicine Respiratory system medicine.medical_specialty vitamin D deficiency Internal medicine Vitamin D and neurology Mechanical ventilation business.industry medicine.disease Steroid hormone business
5015
1 Hewison M. Vitamin D and the intracrinology of innate immunity. Mol Cell Endocrinol 2010;321:103-11.
2 Chun RF, Lauridsen AL, Suon L, et al. Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 2010;95:3368-76.
3 Sabetta JR, DePetrillo P, Cipriani RJ, et al. Serum 25-hydroxyvitamin D and the incidence of acute viral respiratory tract infections in healthy adults. PLoS One 2010;5:e11088. [OpenAIRE]
4 Monlezun DJ, Bittner EA, Christopher KB, et al. Vitamin D status and acute respiratory infection: cross sectional results from the United States National health and nutrition examination survey, 2001-2006. Nutrients 2015;7:1933-44.
5 Dancer RCA, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax 2015;70:617-24. [OpenAIRE]
6 Meltzer DO, Best TJ, Zhang H, et al. Association of vitamin D status and other clinical characteristics with COVID-19 test results. JAMA Netw Open 2020;3:e2019722.
7 Kaufman HW, Niles JK, Kroll MH, et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One 2020;15:e0239252.
8 Papadimitriou DT, Vassaras AK, Holick MF. Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: an ecological integrative approach. World J Virol 2021;10:111-29.
9 Quraishi SA, Camargo CA. Vitamin D in acute stress and critical illness. Curr Opin Clin Nutr Metab Care 2012;15:625-34.
10 Mathyssen C, Gayan-Ramirez G, Bouillon R, et al. Vitamin D supplementation in respiratory diseases: evidence from randomized controlled trials. Pol Arch Intern Med 2017;127:775-84.
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).6 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% views 22 downloads 41 citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).6 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% - 22views41downloads
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This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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Funded byView all
WT| Understanding cross-reactive immunity to Japanese encephalitis virus, EC| PREPARE, UKRI| Human infection challenge vaccine (HIC-vac) network
Project
- Wellcome Trust (WT)
- 205228
- Pathogen Biology and Disease Transmission
, UKRI| ISARIC - Coronavirus Clinical Characterisation Consortium (ISARIC-4C)
Project
- UK Research and Innovation (UKRI)
- MC_PC_19059
- MRC
Project
- UK Research and Innovation (UKRI)
- MR/R005982/1
- MRC
Related to Research communities
- Imperial College London United Kingdom
- University of Edinburgh United Kingdom
- University of Oxford United Kingdom
- St Thomas' Hospital United Kingdom
- King's College London United Kingdom
- Guy's and St Thomas' NHS Foundation Trust United Kingdom
- University of Cambridge United Kingdom
- National Institutes of Health United States
- Boston Children's Hospital United States
- Queen's University Canada
- University of Salford United Kingdom
- Edinburgh Royal Infirmary United Kingdom
- University of Liverpool United Kingdom
ObjectivesThe 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.DesignCross-sectional study.Setting and participantsPlasma 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 measuresReceipt of invasive mechanical ventilation (IMV) and in-hospital mortality.ResultsVitamin 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.ConclusionsVitamin 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.