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

DOI record: { "DOI": "10.1101/2020.10.05.20206706", "URL": "http://dx.doi.org/10.1101/2020.10.05.20206706", "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>", "accepted": { "date-parts": [ [ 2020, 10, 6 ] ] }, "author": [ { "affiliation": [], "family": "Faniyi", "given": "Aduragbemi A", "sequence": "first" }, { "affiliation": [], "family": "Lugg", "given": "Sebastian T", "sequence": "additional" }, { "affiliation": [], "family": "Faustini", "given": "Sian E", "sequence": "additional" }, { "affiliation": [], "family": "Webster", "given": "Craig", "sequence": "additional" }, { "affiliation": [], "family": "Duffy", "given": "Joanne E", "sequence": "additional" }, { "affiliation": [], "family": "Hewison", "given": "Martin", "sequence": "additional" }, { "affiliation": [], "family": "Shields", "given": "Adrian", "sequence": "additional" }, { "affiliation": [], "family": "Nightingale", "given": "Peter", "sequence": "additional" }, { "affiliation": [], "family": "Richter", "given": "Alex G", "sequence": "additional" }, { "affiliation": [], "family": "Thickett", "given": "David R", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2020, 10, 6 ] ], "date-time": "2020-10-06T18:20:33Z", "timestamp": 1602008433000 }, "deposited": { "date-parts": [ [ 2021, 4, 6 ] ], "date-time": "2021-04-06T12:41:51Z", "timestamp": 1617712911000 }, "group-title": "Endocrinology (including Diabetes Mellitus and Metabolic Disease)", "indexed": { "date-parts": [ [ 2024, 4, 8 ] ], "date-time": "2024-04-08T08:36:14Z", "timestamp": 1712565374758 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 7, "issued": { "date-parts": [ [ 2020, 10, 6 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2020.10.05.20206706", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2020, 10, 6 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2020, 10, 6 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "key": "2020101914500680000_2020.10.05.20206706v1.1", "unstructured": "WHO Coronavirus Disease (COVID-19) Dashboard. 2020. https://covid19.who.int/ (accessed Oct 5, 2020)." }, { "DOI": "10.3390/nu7064240", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.2" }, { "DOI": "10.1136/thoraxjnl-2014-206680", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.3" }, { "DOI": "10.1097/CCM.0000000000002095", "article-title": "Vitamin D Deficiency in Human and Murine Sepsis", "doi-asserted-by": "crossref", "first-page": "282", "issue": "2", "journal-title": "Crit Care Med", "key": "2020101914500680000_2020.10.05.20206706v1.4", "volume": "45", "year": "2017" }, { "DOI": "10.1016/S0140-6736(20)30211-7", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.5" }, { "DOI": "10.1097/CCM.0000000000003405", "article-title": "Vitamin D to Prevent Lung Injury Following Esophagectomy-A Randomized, Placebo-Controlled Trial", "doi-asserted-by": "crossref", "first-page": "e1128", "issue": "12", "journal-title": "Crit Care Med", "key": "2020101914500680000_2020.10.05.20206706v1.6", "volume": "46", "year": "2018" }, { "DOI": "10.1016/S2213-8587(20)30183-2", "article-title": "Vitamin-D and COVID-19: do deficient risk a poorer outcome?", "doi-asserted-by": "crossref", "first-page": "570", "issue": "7", "journal-title": "Lancet Diabetes Endocrinol", "key": "2020101914500680000_2020.10.05.20206706v1.7", "volume": "8", "year": "2020" }, { "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)." }, { "DOI": "10.1136/bmjnph-2020-000110", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.9", "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." }, { "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)." }, { "DOI": "10.1186/s12889-017-4436-z", "article-title": "Vitamin D levels and deficiency with different occupations: a systematic review", "doi-asserted-by": "crossref", "first-page": "519", "issue": "1", "journal-title": "BMC Public Health", "key": "2020101914500680000_2020.10.05.20206706v1.11", "volume": "17", "year": "2017" }, { "DOI": "10.1136/thoraxjnl-2020-215414", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.12", "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": "10.1101/2020.06.16.20133025", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.13", "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." }, { "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)." }, { "DOI": "10.1126/science.abb9983", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.15" }, { "DOI": "10.1126/science.abb2507", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.16" }, { "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" }, { "DOI": "10.1093/ageing/afu093", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.18" }, { "DOI": "10.1258/000456306778904614", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.19" }, { "DOI": "10.1258/acb.2012.011249", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.20" }, { "DOI": "10.21203/rs.3.rs-49674/v1", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.21", "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": "10.1371/journal.pone.0239252", "article-title": "SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels", "doi-asserted-by": "crossref", "first-page": "e0239252", "issue": "9", "journal-title": "PLoS One", "key": "2020101914500680000_2020.10.05.20206706v1.22", "volume": "15", "year": "2020" }, { "DOI": "10.1101/2020.07.01.20144329", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.23", "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": "10.1136/bmj.i6583", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.24" }, { "DOI": "10.1136/postgradmedj-2020-138712", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.25", "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": "10.2174/18715281113129990049", "doi-asserted-by": "publisher", "key": "2020101914500680000_2020.10.05.20206706v1.26" }, { "DOI": "10.1111/cen.14310", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.27", "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": "10.1007/s40618-020-01370-x", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.28", "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": "10.1016/j.ijid.2020.08.018", "doi-asserted-by": "crossref", "key": "2020101914500680000_2020.10.05.20206706v1.29", "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.dsx.2020.04.050", "article-title": "Vitamin D concentrations and COVID-19 infection in UK Biobank", "doi-asserted-by": "crossref", "first-page": "561", "issue": "4", "journal-title": "Diabetes Metab Syndr", "key": "2020101914500680000_2020.10.05.20206706v1.30", "volume": "14", "year": "2020" }, { "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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