Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic

{ 'institution': [{'name': 'medRxiv'}], 'indexed': {'date-parts': [[2024, 4, 8]], 'date-time': '2024-04-08T08:36:14Z', 'timestamp': 1712565374758}, 'posted': {'date-parts': [[2020, 10, 6]]}, 'group-title': 'Endocrinology (including Diabetes Mellitus and Metabolic Disease)', 'reference-count': 31, 'publisher': 'Cold Spring Harbor Laboratory', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'accepted': {'date-parts': [[2020, 10, 6]]}, 'abstract': '<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>It is ' 'clear that in UK healthcare workers, COVID-19 infections and deaths were more likely to be in ' 'staff who were of BAME origin. This has led to much speculation about the role of vitamin D ' 'in healthcare worker COVID-19 infections. We aimed to determine the prevalence of vitamin D ' 'deficiency in NHS staff who have isolated with symptoms suggestive of COVID-19 and relate ' 'this to vitamin D ' 'status.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We recruited NHS ' 'healthcare workers between 12<jats:sup>th</jats:sup>to 22<jats:sup>nd</jats:sup>May 2020 as ' 'part of the COVID-19 convalescent immunity study (COCO). We measured anti-SARS-Cov-2 ' 'antibodies using a combined IgG, IgA and IgM ELISA (The Binding Site). Vitamin D status was ' 'determined by measurement of serum 25(OH)D<jats:sub>3</jats:sub>using the AB SCIEX Triple ' 'Quad 4500 mass spectrometry ' 'system.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Of the 392 NHS ' 'healthcare workers, 214 (55%) had seroconverted for COVID-19. A total of 61 (15.6%) members ' 'of staff were vitamin D deficient (&lt;30 nmol/l) with significantly more staff from BAME ' 'backgrounds or in a junior doctor role being deficient. Vitamin D levels were lower in those ' 'who were younger, had a higher BMI (&gt;30 kg/m<jats:sup>2</jats:sup>), and were male. ' 'Multivariate analysis revealed that BAME and COVID-19 seroconversion were independent ' 'predictors of vitamin D deficiency. Staff who were vitamin D deficient were more likely to ' 'self-report symptoms of body aches and pains but importantly not the respiratory symptoms of ' 'cough and breathlessness. Vitamin D levels were lower in those COVID-19 positive staff who ' 'reported fever, but this did not reach statistical significance. Within the whole cohort ' 'there was an increase in seroconversion in staff with vitamin D deficiency compared to those ' 'without vitamin D deficiency (n=44/61, 72%<jats:italic>vs</jats:italic>n=170/331, 51%; ' 'p=0·003); this was particularly marked in the proportion of BAME males who were vitamin D ' 'deficient compared to non-vitamin D deficient BAME males (n=17/18, ' '94%<jats:italic>vs</jats:italic>n=12/23, 52%; p=0·005). Multivariate analysis revealed that ' 'vitamin D deficiency was an independent risk factor for seroconversion (OR 2·6, 95%CI ' '1·41–4·80; ' 'p=0·002).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>In ' 'those healthcare workers who have isolated due to symptoms of COVID-19, those of BAME ' 'ethnicity are at the highest risk of vitamin D deficiency. Vitamin D deficiency is a risk ' 'factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male ' 'staff.</jats:p></jats:sec><jats:sec><jats:title>Funding</jats:title><jats:p>This study was ' 'funded internally by the University of Birmingham and University Hospitals Birmingham NHS ' 'Foundation Trust and supported by the National Institute for Health Research (NIHR)/Wellcome ' 'Trust Birmingham Clinical Research Facility. AAF and DRT are funded by the Medical Research ' 'Council (MR/S002782/1). The Binding Site (Edgbaston, UK) have provided reagents and plates ' 'for the SARS-CoV-2 ELISA free of charge.</jats:p></jats:sec><jats:sec><jats:title>Research in ' 'context</jats:title><jats:sec><jats:title>Evidence before this study</jats:title><jats:p>The ' 'ongoing COVID-19 pandemic has raised several questions, one of which is whether individuals ' 'with vitamin D deficiency were at a greater risk of being infected or having a severe outcome ' 'if infected. Among UK healthcare workers, and indeed the general population, individuals of ' 'BAME ethnicity are disproportionately affected by COVID-19. It is well established that ' 'individuals of BAME ethnicity have a higher prevalence of vitamin D deficiency, but it is ' 'unknown if vitamin D deficiency among UK NHS workers was connected to the risk of COVID-19 ' 'infection. Our search of the literature revealed no previous studies have established the ' 'prevalence of vitamin D deficiency within a UK NHS trust. Unsurprisingly, there is also no ' 'evidence to suggest if vitamin D deficiency was connected to the risk of infection among UK ' 'healthcare workers.</jats:p></jats:sec><jats:sec><jats:title>Added value of this ' 'study</jats:title><jats:p>In this study of healthcare workers who had isolated for COVID-19 ' 'symptoms towards the end of UK surge within a large UK NHS trust, 15.6% were vitamin D ' 'deficient. Our data also reveal that healthcare workers of BAME ethnicity and those who had ' 'seroconverted for COVID-19 were more likely to be vitamin D deficient. Multivariate analysis ' 'also show that vitamin D deficiency was the only predictor of COVID-19 seroconversion. ' 'Vitamin D deficient healthcare workers that are BAME and male had a 94% seroconversion for ' 'COVID-19 compared to non-deficient BAME males suggesting they are more at risk of COVID-19 if ' 'vitamin D deficient.</jats:p></jats:sec><jats:sec><jats:title>Implications of all the ' 'available evidence</jats:title><jats:p>There is an increased risk of COVID-19 infection in ' 'healthcare workers with vitamin D deficiency. Our data adds to the emerging evidence from ' 'studies in the UK and across the globe that individuals with severe COVID-19 are more vitamin ' 'D deficient than those with mild disease. Finally, ours and the available evidence ' 'demonstrate vitamin D supplementation in individuals at risk of vitamin D deficiency or shown ' 'to be deficient may help alleviate the impact of COVID-19.</jats:p></jats:sec></jats:sec>', 'DOI': '10.1101/2020.10.05.20206706', 'type': 'posted-content', 'created': {'date-parts': [[2020, 10, 6]], 'date-time': '2020-10-06T18:20:33Z', 'timestamp': 1602008433000}, 'source': 'Crossref', 'is-referenced-by-count': 7, 'title': 'Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for ' 'COVID-19 like symptoms during the 2020 pandemic', 'prefix': '10.1101', 'author': [ {'given': 'Aduragbemi A', 'family': 'Faniyi', 'sequence': 'first', 'affiliation': []}, {'given': 'Sebastian T', 'family': 'Lugg', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sian E', 'family': 'Faustini', 'sequence': 'additional', 'affiliation': []}, {'given': 'Craig', 'family': 'Webster', 'sequence': 'additional', 'affiliation': []}, {'given': 'Joanne E', 'family': 'Duffy', 'sequence': 'additional', 'affiliation': []}, {'given': 'Martin', 'family': 'Hewison', 'sequence': 'additional', 'affiliation': []}, {'given': 'Adrian', 'family': 'Shields', 'sequence': 'additional', 'affiliation': []}, {'given': 'Peter', 'family': 'Nightingale', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alex G', 'family': 'Richter', 'sequence': 'additional', 'affiliation': []}, {'given': 'David R', 'family': 'Thickett', 'sequence': 'additional', 'affiliation': []}], 'member': '246', 'reference': [ { 'key': '2020101914500680000_2020.10.05.20206706v1.1', 'unstructured': 'WHO Coronavirus Disease (COVID-19) Dashboard. 2020. ' 'https://covid19.who.int/ (accessed Oct 5, 2020).'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.2', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7064240'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.3', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/thoraxjnl-2014-206680'}, { 'issue': '2', 'key': '2020101914500680000_2020.10.05.20206706v1.4', 'doi-asserted-by': 'crossref', 'first-page': '282', 'DOI': '10.1097/CCM.0000000000002095', 'article-title': 'Vitamin D Deficiency in Human and Murine Sepsis', 'volume': '45', 'year': '2017', 'journal-title': 'Crit Care Med'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.5', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30211-7'}, { 'issue': '12', 'key': '2020101914500680000_2020.10.05.20206706v1.6', 'doi-asserted-by': 'crossref', 'first-page': 'e1128', 'DOI': '10.1097/CCM.0000000000003405', 'article-title': 'Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, ' 'Placebo-Controlled Trial', 'volume': '46', 'year': '2018', 'journal-title': 'Crit Care Med'}, { 'issue': '7', 'key': '2020101914500680000_2020.10.05.20206706v1.7', 'doi-asserted-by': 'crossref', 'first-page': '570', 'DOI': '10.1016/S2213-8587(20)30183-2', 'article-title': 'Vitamin-D and COVID-19: do deficient risk a poorer outcome?', 'volume': '8', 'year': '2020', 'journal-title': 'Lancet Diabetes Endocrinol'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.8', 'unstructured': 'Office for National Statistics. Coronavirus (COVID-19) related deaths by ' 'ethnic group, England and Wales: 2 March 2020 to 10 April 2020. ' 'https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/coronavirusrelateddeathsbyethnicgroupenglandandwales/2march2020to10april2020 ' '(accessed Oct 5, 2020).'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.9', 'doi-asserted-by': 'crossref', 'unstructured': 'Rhodes J , Dunstan F , Laird E , Subramanian S , Kenny RA . COVID-19 ' 'mortality increases with northerly latitude after adjustment for age ' 'suggesting a link with ultraviolet and vitamin D. BMJ Nutrition, ' 'Prevention &amp; Health 2020: bmjnph-2020-000110.', 'DOI': '10.1136/bmjnph-2020-000110'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.10', 'unstructured': 'Exclusive: deaths of NHS staff from covid-19 analysed. 2020. ' 'https://www.hsj.co.uk/exclusive-deaths-of-nhs-staff-from-covid-19-analysed/7027471.article ' '(accessed Oct 5, 2020).'}, { 'issue': '1', 'key': '2020101914500680000_2020.10.05.20206706v1.11', 'doi-asserted-by': 'crossref', 'first-page': '519', 'DOI': '10.1186/s12889-017-4436-z', 'article-title': 'Vitamin D levels and deficiency with different occupations: a ' 'systematic review', 'volume': '17', 'year': '2017', 'journal-title': 'BMC Public Health'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.12', 'doi-asserted-by': 'crossref', 'unstructured': 'Shields A , Faustini SE , Perez-Toledo M , et al. SARS-CoV-2 ' 'seroprevalence and asymptomatic viral carriage in healthcare workers: a ' 'cross-sectional study. Thorax 2020.', 'DOI': '10.1136/thoraxjnl-2020-215414'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.13', 'doi-asserted-by': 'crossref', 'unstructured': 'Faustini SE , Jossi SE , Perez-Toledo M , et al. Detection of antibodies ' 'to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances ' 'detection of infection. medRxiv 2020.', 'DOI': '10.1101/2020.06.16.20133025'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.14', 'unstructured': 'Binding Site . Human Anti-IgG/A/M SARS-CoV-2 ELISA / Performance ' 'Characteristics / Clinical Performance. 2020. ' 'https://www.bindingsite.com/en/our-products/covid-19/sars-cov-2-elisa/performance-characteristics/clinical-performance ' '(accessed Oct 5, 2020).'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.15', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.abb9983'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.16', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.abb2507'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.17', 'unstructured': 'Institute of Medicine. Dietary reference intakes for calcium and vitamin ' 'D. Washington, DC: The National Academies Press 2011'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.18', 'doi-asserted-by': 'publisher', 'DOI': '10.1093/ageing/afu093'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.19', 'doi-asserted-by': 'publisher', 'DOI': '10.1258/000456306778904614'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.20', 'doi-asserted-by': 'publisher', 'DOI': '10.1258/acb.2012.011249'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.21', 'doi-asserted-by': 'crossref', 'unstructured': 'Mahida RY , Chotalia M , Alderman J , et al. Characterization and ' 'Outcomes of ARDS secondary to pneumonia in patients with and without ' 'SARS-CoV-2: A single center experience. Research Square 2020.', 'DOI': '10.21203/rs.3.rs-49674/v1'}, { 'issue': '9', 'key': '2020101914500680000_2020.10.05.20206706v1.22', 'doi-asserted-by': 'crossref', 'first-page': 'e0239252', 'DOI': '10.1371/journal.pone.0239252', 'article-title': 'SARS-CoV-2 positivity rates associated with circulating ' '25-hydroxyvitamin D levels', 'volume': '15', 'year': '2020', 'journal-title': 'PLoS One'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.23', 'doi-asserted-by': 'crossref', 'unstructured': 'Merzon E , Tworowski D , Gorohovski A , et al. Low plasma 25(OH) vitamin ' 'D level is associated with increased risk of COVID-19 infection: an ' 'Israeli population-based study. Febs j 2020.', 'DOI': '10.1101/2020.07.01.20144329'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.24', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj.i6583'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.25', 'doi-asserted-by': 'crossref', 'unstructured': 'Baktash V , Hosack T , Patel N , et al. Vitamin D status and outcomes ' 'for hospitalised older patients with COVID-19. Postgrad Med J 2020.', 'DOI': '10.1136/postgradmedj-2020-138712'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.26', 'doi-asserted-by': 'publisher', 'DOI': '10.2174/18715281113129990049'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.27', 'doi-asserted-by': 'crossref', 'unstructured': 'Panagiotou G , Tee SA , Ihsan Y , et al. Low serum 25-hydroxyvitamin D ' '(25[OH]D) levels in patients hospitalized with COVID-19 are associated ' 'with greater disease severity. Clin Endocrinol (Oxf) 2020.', 'DOI': '10.1111/cen.14310'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.28', 'doi-asserted-by': 'crossref', 'unstructured': 'Carpagnano GE , Di Lecce V , Quaranta VN , et al. Vitamin D deficiency ' 'as a predictor of poor prognosis in patients with acute respiratory ' 'failure due to COVID-19. J Endocrinol Invest 2020: 1–7.', 'DOI': '10.1007/s40618-020-01370-x'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.29', 'doi-asserted-by': 'crossref', 'unstructured': 'Im JH , Je YS , Baek J , Chung MH , Kwon HY , Lee JS . Nutritional ' 'status of patients with coronavirus disease 2019 (COVID-19). Int J ' 'Infect Dis 2020.', 'DOI': '10.1016/j.ijid.2020.08.018'}, { 'issue': '4', 'key': '2020101914500680000_2020.10.05.20206706v1.30', 'doi-asserted-by': 'crossref', 'first-page': '561', 'DOI': '10.1016/j.dsx.2020.04.050', 'article-title': 'Vitamin D concentrations and COVID-19 infection in UK Biobank', 'volume': '14', 'year': '2020', 'journal-title': 'Diabetes Metab Syndr'}, { 'key': '2020101914500680000_2020.10.05.20206706v1.31', 'first-page': '105751', 'article-title': '“Effect of calcifediol treatment and best available therapy versus best ' 'available therapy on intensive care unit admission and mortality among ' 'patients hospitalized for COVID-19: A pilot randomized clinical study”. 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