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
doi:10.1101/2020.06.21.20136903
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.
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"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<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>",
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