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0 0.5 1 1.5 2+ ICU admission 52% Improvement Relative Risk Vitamin D for COVID-19  Panagiotou et al.  Sufficiency Are vitamin D levels associated with COVID-19 outcomes? Retrospective 134 patients in the United Kingdom Lower ICU admission with higher vitamin D levels (p=0.02) Panagiotou et al., medRxiv, June 2020 Favors vitamin D Favors control

Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice

Panagiotou et al., medRxiv, doi:10.1101/2020.06.21.20136903
Jun 2020  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
*, now known with p < 0.00000000001 from 120 studies, recognized in 8 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments.
Retrospective analysis 134 hospitalized patients. 19% of ICU patients had 25(OH)D levels > 50 nmol/L vs. 39.1% of non-ICU patients, p=0.02
This is the 4th of 196 COVID-19 sufficiency studies for vitamin D, which collectively show higher levels reduce risk with p<0.0000000001 (1 in 11,637 vigintillion).
risk of ICU admission, 52.0% lower, RR 0.48, p = 0.02, high D levels 8 of 44 (18.2%), low D levels 34 of 90 (37.8%), NNT 5.1, >50nmol/L.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Panagiotou et al., 30 Jun 2020, retrospective, United Kingdom, preprint, 12 authors.
This PaperVitamin DAll
Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice
Grigorios Panagiotou, Su Ann Tee, Yasir Ihsan, Waseem Athar, Gabriella Marchitelli, Donna Kelly, Christopher S Boot, Nadia Stock, James Macfarlane, Adrian R Martineau, Graham Burns, Dr Richard Quinton
Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.
manuscript. RQ is the guarantor of this work and attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Alipio, Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus, COVID
Aranow, Vitamin D and the immune system, Journal of investigative medicine : the official publication of the American Federation for Clinical Research, doi:10.2310/JIM.0b013e31821b8755
Aspell, Laird, Healy, The Prevalence and Determinants of Vitamin D Status in Community-Dwelling Older Adults: Results from the English Longitudinal Study of Ageing (ELSA), Nutrients, doi:10.3390/nu11061253
Berry, Hesketh, Power, Vitamin D status has a linear association with seasonal infections and lung function in British adults, The British journal of nutrition, doi:10.1017/S0007114511001991
Covid, 19 and Vitamin D Supplementation: a Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients
Daneshkhah, Agrawal, Eshein, The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients, medRxiv, doi:10.1101/2020.04.08.20058578
Glicio, Vitamin D Level of Mild and Severe Elderly Cases of COVID-19: A Preliminary Report
Goldacre, Hall, Yeates, Hospitalisation for children with rickets in England: a historical perspective, Lancet, doi:10.1016/S0140-6736(14)60211-7
Grant, Lahore, Mcdonnell, Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients, doi:10.3390/nu12040988
Gruber-Bzura, Vitamin D and Influenza-Prevention or Therapy?, International journal of molecular sciences, doi:10.3390/ijms19082419
Hastie, Mackay, Ho, Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes & metabolic syndrome, doi:10.1016/j.dsx.2020.04.050
Hill, Granic, Davies, Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis, Foundation, doi:10.1007/s00198-015-3366-9
Hypponen, Power, Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors, The American journal of clinical nutrition, doi:10.1093/ajcn/85.3.860
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging clinical and experimental research, doi:10.1007/s40520-020-01570-8
Jin, Bai, He, Gender Differences in Patients With COVID-19: Focus on Severity and Mortality, Frontiers in public health, doi:10.3389/fpubh.2020.00152
Jolliffe, Stefanidis, Wang, Vitamin D Metabolism is Dysregulated in Asthma and Chronic Obstructive Pulmonary Disease, American journal of respiratory and critical care medicine, doi:10.1164/rccm.201909-1867OC
Khare, Godbole, Pawar, None, Calcitriol
Khunti, De Bono, Browne, Risk Reduction Framework for NHS staff at risk of COVID-19 infection, Faculty of Occupational Medicine
Khunti, Singh, Pareek, Is ethnicity linked to incidence or outcomes of covid-19?, Bmj, doi:10.1136/bmj.m1548
Lau, Majumder, Torabi, Vitamin D Insufficiency is Prevalent in Severe COVID-19, medRxiv, doi:10.1101/2020.04.24.20075838
Martineau, Jolliffe, Hooper, Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, Bmj, doi:10.1136/bmj.i6583
Nonnecke, Mcgill, Ridpath, Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves, Journal of dairy science, doi:10.3168/jds.2014-8293
Pap, Sadiah, Budiarti, Agung, Budi, Patterns of COVID-19 Mortality and Vitamin D: An Indonesian Study
Pearce, Cheetham, Diagnosis and management of vitamin D deficiency, Bmj, doi:10.1136/bmj.b5664
Pereira-Santos, Costa, Assis, Obesity and vitamin D deficiency: a systematic review and meta-analysis, International Association for the Study of Obesity, doi:10.1111/obr.12239
Rhodes, Subramanian, Laird, Editorial: low population mortality from COVID-19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity, Alimentary pharmacology & therapeutics, doi:10.1111/apt.15777
Romagnoli, Mascia, Cipriani, Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly, The Journal of clinical endocrinology and metabolism, doi:10.1210/jc.2008-0350
Ruiz-Irastorza, Egurbide, Olivares, Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences, Rheumatology, doi:10.1093/rheumatology/ken121
Silberstein, Vitamin, A simpler alternative to tocilizumab for trial in COVID-19?, Medical hypotheses, doi:10.1016/j.mehy.2020.109767
{ 'DOI': '10.1101/2020.06.21.20136903', 'URL': '', 'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>To ' 'audit implementation of a local protocol for the treatment of vitamin D deficiency (VDD) ' 'among patients hospitalized for Coronavirus Disease 2019 (COVID-19), including an assessment ' 'of the prevalence of VDD in these patients, and of potential associations with disease ' 'severity and ' 'fatality.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>This was not a ' 'study or clinical trial, but rather a retrospective interim audit (Newcastle-upon-Tyne ' 'Hospitals Registration No. 10075) of a local clinical care pathway for hospitalized patients ' 'with COVID-19-related illness. The Information (Caldicott) Guardian permitted these data to ' 'be shared beyond the confines of our ' 'institution.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>A large ' 'tertiary academic NHS Foundation Trust in the North East of England, UK, providing care to ' 'COVID-19 ' 'patients.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>One ' 'hundred thirty-four hospitalized patients with documented COVID-19 ' 'infection.</jats:p></jats:sec><jats:sec><jats:title>Main outcome ' 'measures</jats:title><jats:p>Adherence to local investigation and treatment protocol; ' 'prevalence of VDD, and relationship of baseline serum 25(OH)D with markers of COVID-19 ' 'severity and inpatient fatality versus ' 'recovery.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>55.8% of ' 'eligible patients received Colecalciferol replacement, albeit not always loaded as rapidly as ' 'our protocol suggested, and no cases of new hypercalcaemia occurred following treatment. ' 'Patients admitted to ITU were younger than those managed on medical wards (61.1 years ± 11.8 ' '<jats:italic>vs</jats:italic>. 76.4 years ± 14.9, p&lt;0.001), with greater prevalence of ' 'hypertension, and higher baseline respiratory rate, National Early Warning Score-2 and ' 'C-reactive protein level. While mean serum 25(OH)D levels were comparable ' '[<jats:italic>i</jats:italic>.<jats:italic>e</jats:italic>. ITU: 33.5 nmol/L ± 16.8 ' '<jats:italic>vs</jats:italic>. Non-ITU: 48.1 nmol/L ± 38.2, mean difference for ' 'Ln-transformed-25(OH)D: 0.14, 95% Confidence Interval (CI) (−0.15, 0.41), p=0.3], only 19% of ' 'ITU patients had 25(OH)D levels greater than 50 nmol/L <jats:italic>vs</jats:italic>. 39.1% ' 'of non-ITU patients (p=0.02). However, we found no association with fatality, potentially due ' 'to small sample size, limitations of no-trial data and, potentially, the prompt diagnosis and ' 'treatment of ' 'VDD.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Subject to the ' 'inherent limitations of observational (non-trial) audit data, analysed retrospectively, we ' 'found that patients requiring ITU admission were more frequently vitamin D deficient than ' 'those managed on medical wards, despite being significantly younger. Larger prospective ' 'studies and/or clinical trials are needed to elucidate the role of vitamin D as a preventive ' 'and/or therapeutic strategy for mitigating the effects of COVID-19 infection in patients with ' 'VDD.</jats:p></jats:sec><jats:sec><jats:title>What is already known on this ' 'topic</jats:title><jats:list list-type="bullet"><jats:list-item><jats:p>Vitamin D deficiency ' '(VDD) is associated with increased risk for acute respiratory tract ' 'infections</jats:p></jats:list-item><jats:list-item><jats:p>A link between VDD and severity ' 'of COVID-19 pathophysiology has been ' 'proposed</jats:p></jats:list-item><jats:list-item><jats:p>Two recent (non-peer-reviewed) ' 'studies have reported crude associations between VDD in defined geographic populations and ' 'COVID-19 severity and ' 'mortality</jats:p></jats:list-item></jats:list></jats:sec><jats:sec><jats:title>What this ' 'study adds</jats:title><jats:list ' 'list-type="bullet"><jats:list-item><jats:p><jats:italic>These data do not arise from a ' 'clinical study</jats:italic>; rather from an audit of a local replacement protocol for VDD in ' 'COVID-19 inpatients in a large UK centre, which found a significantly higher prevalence of ' 'VDD among ITU patients compared to non-ITU patients, despite the ITU patients being ' 'significantly younger.</jats:p></jats:list-item><jats:list-item><jats:p>Prompt treatment of ' 'VDD following a local protocol did not result in any adverse events, such as ' 'hypercalcaemia.</jats:p></jats:list-item><jats:list-item><jats:p>Whilst by no means ' 'conclusive, these data suggest an important association between VDD and COVID-19 severity; ' 'hence our report of interim findings in advance of achieving completed outcomes (fatality ' '<jats:italic>vs</jats:italic>. recovery) for all ' 'patients.</jats:p></jats:list-item><jats:list-item><jats:p>There is an urgent need for larger ' 'studies exploring vitamin D as a potential preventative measure and/or treatment of ' 'Covid-19-related illness among individuals with ' 'VDD.</jats:p></jats:list-item></jats:list></jats:sec>', 'accepted': {'date-parts': [[2020, 6, 25]]}, 'author': [ { 'ORCID': '', 'affiliation': [], 'authenticated-orcid': False, 'family': 'Panagiotou', 'given': 'Grigorios', 'sequence': 'first'}, {'affiliation': [], 'family': 'Tee', 'given': 'Su Ann', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Ihsan', 'given': 'Yasir', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Athar', 'given': 'Waseem', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Marchitelli', 'given': 'Gabriella', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Kelly', 'given': 'Donna', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Boot', 'given': 'Christopher S.', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Stock', 'given': 'Nadia', 'sequence': 'additional'}, {'affiliation': [], 'family': 'Macfarlane', 'given': 'James', 'sequence': 'additional'}, 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