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
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Abstract
Objectives
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.
Design
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.
Setting
A large tertiary academic NHS Foundation Trust in the North East of England, UK, providing care to COVID-19 patients.
Participants
One hundred thirty-four hospitalized patients with documented COVID-19 infection.
Main outcome measures
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.
Results
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 vs . 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 [ i . e . ITU: 33.5 nmol/L ± 16.8 vs . 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 vs . 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.
Conclusions
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.
What is already known on this topic
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Vitamin D deficiency (VDD) is associated with increased risk for acute respiratory tract infections
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A link between VDD and severity of COVID-19 pathophysiology has been proposed
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Two recent (non-peer-reviewed) studies have reported crude associations between VDD in defined geographic populations and COVID-19 severity and mortality
What this study adds
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These data do not arise from a clinical study ; 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.
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Prompt treatment of VDD following a local protocol did not result in any adverse events, such as hypercalcaemia.
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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 vs . recovery) for all patients.
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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.
Article activity feed
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SciScore for 10.1101/2020.06.21.20136903: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of these data include the small sample size and the observational nature of this audit. We also acknowledge that the cross-sectional analysis employed herein does not allow causality to be established, particularly …
SciScore for 10.1101/2020.06.21.20136903: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Limitations of these data include the small sample size and the observational nature of this audit. We also acknowledge that the cross-sectional analysis employed herein does not allow causality to be established, particularly given data suggesting that 25OHD may be a negative acute phase reactant due to dysregulated vitamin D metabolism in respiratory disease [31]. Nevertheless, these data provide an important impetus to the commissioning, design and interpretation of ongoing or future multi-center randomized controlled trials, which could conclusively define a therapeutic role of vitamin D in COVID-19. In addition, our population consisted of predominantly Caucasian patients with moderate to severe symptoms from COVID-19 and, given that the vast majority of COVID-19 cases are asymptomatic or mildly symptomatic (not requiring hospital admission), community-based studies are needed to address whether adequate vitamin D concentrations reduce the risk for hospital attendance. We have proactively treated VDD in our patients per our Trust protocol described herein and this might partly explain the lack of association of baseline serum 25(OH)D with fatality. Also, since data collection was performed in a retrospective manner, patients included in this audit may have been actively treated with various other medications as part of clinical research trials to identify successful treatment for COVID-19 and it is therefore almost impossible to adjust for this in the analysis. In conclu...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04344041 Recruiting COvid-19 and Vitamin D Supplementation: a Multicenter Random… NCT04334005 Not yet recruiting Vitamin D on Prevention and Treatment of COVID-19 Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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