key: cord-1052854-0rg339zp
authors: Livingston, Mark; Plant, Aiden; Dunmore, Simon; Hartland, Andrew; Jones, Stephen; Laing, Ian; Ramachandran, Sudarshan
title: Detectable respiratory SARS‐CoV‐2 RNA is associated with low vitamin D levels and high social deprivation
date: 2021-04-24
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14166
sha: cd3e21d807ce2504144d5fa411f0b47ec73773e0
doc_id: 1052854
cord_uid: 0rg339zp

BACKGROUND: Accumulating evidence links COVID‐19 incidence and outcomes with vitamin D status. We investigated if an interaction existed between vitamin D levels and social deprivation in those with and without COVID‐19 infection. METHODS: Upper or lower respiratory tract samples from 104 patients were tested for SARS‐CoV‐2 RNA in accordance with Public Health England criteria (January‐May 2020) using RT‐PCR. The latest serum total 25‐hydroxyvitamin D(25‐OHD) levels, quantified by LC‐MS/MS, was obtained for each patient (September 2019‐April 2020). Index of Multiple Deprivation (IMD) was generated for each patient. Univariate and logistic regression analyses examined associations between age, gender, 25‐OHD, IMD score and SARS‐CoV‐2 result in the total cohort and subgroups. RESULTS: In the total cohort, a positive SARS‐CoV‐2 test was significantly associated with lower 25‐OHD levels and higher IMD. A positive test was associated with higher IMD in the male subgroup and with lower 25‐OHD levels in those aged >72 years. Low 25‐OHD and IMD quintile 5 were separately associated with positive COVID‐19 outcome in the cohort. Patients in IMD quintile 5 with vitamin D levels ≤ 34.4 nmol/L were most likely to have a positive COVID‐19 outcome, even more so if aged >72 years (OR: 19.07, 95%CI: 1.71‐212.25; P = .016). CONCLUSIONS: In this cohort, combined low vitamin D levels and higher social deprivation were most associated with COVID‐19 infection. In older age, this combination was even more significant. Our data support the recommendations for normalising vitamin D levels in those with deficient / insufficient levels and in groups at high risk for deficiency.

accumulating evidence, there have been recommendations that individuals at risk of COVID-19 should consider treatment with inactive vitamin D to reduce the risk of infection: 10 000 IU/day for a few days followed by 5000 IU/day to raise serum 25-OHD concentrations to 100-150 nmol/L. 6, 10 However, although a study by Hastie et al 11 using data from the UK Biobank did show an association between vitamin D levels and COVID-19 infection, this relationship was not sustained when confounders were included in the logistic regression model. Hence, the relationship between vitamin D levels and COVID-19 infection appears complex, and perhaps may only be seen in subgroups. This heterogeneity would make the association very dependent on the cohort studied.

A report from the UK Office for National Statistics suggested that COVID-19-related deaths (20 283 in England and Wales between March 1, 2020, and April 17, 2020) showed a relationship between mortality and deprivation; the age-standardised mortality rate in the most deprived areas of England was 55.1/100 000 population compared with 25.3/100 000 population in the least deprived areas. 12 Hayden et al 13 showed that vitamin D deficiency is related to ethnicity and social deprivation; an association (P = .0001) was The aim of this pilot study was to see whether any differences in serum vitamin D and social deprivation, using the IMD scores, existed between the patient groups with and without a SARS-CoV-2 detected PCR test. We also wished to see if an interaction existed between vitamin D concentration and deprivation with regard to COVID-19. Moreover, the analyses were repeated in subgroups associated with a poorer prognosis, in particular, male gender and older age. Clinical samples of the upper (nasopharyngeal swabs) or lower respiratory tract (sputum or bronchial washings) were tested for the presence of SARS-CoV-2 after inoculation into viral transport medium, using initially reference laboratory investigational RdRPgene real-time reverse-transcriptase PCR assay until 6th April 2020. After this date, detection of SARS-CoV-2 was performed locally on a commercial assay detecting the ORF-1a/b and E-genes with a reported limit of detection of <300 copies/mL (Roche Cobas; Roche Diagnostics GmbH, Manheim, Germany). 16 The relative clinical sensitivity and specificity of these targets are not yet known.

Vitamin D levels were the most recent for each patient, obtained from the Clinical Biochemistry laboratory database, from a period covering 6 months up to and including admission date (between prived is ranked 32 844. Each vitamin D result was aligned with an associated postcode for each patient and linked to its LSOA using the geo-convert tool. 17 The LSOA is then linked to the 2019 IMD for the specified full postcode. 14 This was not possible using geoconvert for six patients included in this study. 18 

The association between a positive SARS-CoV-2 test compared with a negative SARS-CoV-2 test result and serum vitamin D levels, IMD, age and gender was initially studied using unpaired t-test (continuous variables), rank-sum non-parametric test (ordinal data: IMD) in the total cohort and subgroups; age, vitamin D by median values and IMD by the quintile threshold closest to the median. 19 Logistic regression analyses were then carried out with SARS-CoV-2 RNA real-time RT-PCR test result as the dichotomous outcome (detected or not detected) and vitamin D levels and factorised IMD as independent variables with age and gender included as confounders.

The regression analyses were carried out in the total groups and the previously mentioned subgroups. All analyses were performed on Stata 14 (StataCorp LLC, Texas, USA).

In the total cohort of 104 individuals tested for SARS-CoV-2, a positive result was significantly associated with low vitamin D concentrations and IMD, but not age and gender ( Table 1 ). The total cohort was then stratified by gender, median age (72 years), vitamin D levels (Table 1) .

We then performed a logistic regression analysis with COVID-19 positive diagnosis (reference: negative diagnosis) as the dichotomous outcome. Low vitamin D levels and IMD quintile 5 (compared with IMD quintiles 1-4) were significantly associated with the outcome whilst age and gender were not ( 

There is accumulating evidence on the association between vitamin D levels and COVID-19 incidence and outcome following infection. [6] [7] [8] 20 Ours is a relatively small study cohort fulfiling the PCR-based testing criteria for COVID-19. Univariate analyses showed that low In conclusion, combined low vitamin D levels and higher social deprivation were most associated with COVID-19 infection. In older age, this combination was even more significant. The importance of studying subgroups and acknowledging heterogeneity is highlighted, with results being dependant on the cohort studied.

The authors acknowledge Mr Yusuf Varachia for help with extracting the data from the laboratory database.

A preprint of this publication in the Authorea repository: https:// w w w.autho rea.com/users/ 31229 6/ar tic les/45494 0-detec table -respi rator y-sars-cov-2-rna-is-assoc iated -with-low-vitam in-d-level s-and-high-socia l-depri vatio n?commi t=0a10e c6dd5 905a5 d7177 61c9e a66e9 e366c a1f7d

None to declare.

We used patient level data which was fully anonymised prior to analysis. Any requests for access to this data should be made to the corresponding author, Prof Mark Livingston.

Mark Livingston https://orcid.org/0000-0001-6878-0769

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