SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels
PLoS ONE 15(9): e0239252. https://doi.org/10.1371/journal.pone.0239252
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Note; This association may be just due to elderly having low vitamin D and testing positive.
Chart is not age-adjusted
Higher rate if lower Vitamin D test
Graphic made from the data by www.vitaminDJournal.de
Higher rate of test positive if further from Equator
Higher rate of test positive if darker skin
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Expression of Concern by editors of PLOS1
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- Concerns were raised about the reported study’s sample size and whether it was adequate to address the aims of the study.
- Questions were raised about whether the statistical analyses and results were sufficiently robust to support the article’s conclusions, and about how potential confounds were addressed in the data analyses. As one aspect of this, it was raised that vitamin D levels may be indicative of co-morbidities that may themselves impact COVID outcomes.
- There are statements in the article, including in its title and conclusions, that suggest a causal relationship between vitamin D levels and the clinical outcome of COVID-19 infections which is not supported by the data.
- Of the participants in the study, only 31.06% had RT-PCR tests confirming a COVID-19 diagnosis. As such, the COVID-19 status of other participants is in question, although in the article all are reported as patients with COVID-19. This is not taken into consideration in the subgroup analyses as reported in the article, and calls into question the overall interpretation of the results.
- The article’s Competing Interests statement says, “The authors have declared that no competing interests exist.” However, publicly available information indicates that corresponding author MFH may have potential competing interests that include non-financial interests based on his vitamin D research and other activities focused on vitamin D; contributions to an app that tracks vitamin D; and interests that include consultancies, funding support, and authorship of books related to vitamin D usage.
- The authors commented that the article did not claim a causal role of vitamin D on clinical outcomes, and that the limitations of the study were clearly described in the Discussion which said, “we cannot explain the cause and effect relationship of vitamin D sufficiency and the reduced risk of severity from a COVID-19 infection.” [1] They also stated that COVID-19 diagnoses were made by infectious disease specialists per WHO interim guidance and recommendations of the Iranian National Committee of COVID-19 [2].
- PLOS ONE is currently reassessing the article and following up on the above issues in accordance with COPE guidance and journal policies. Meanwhile, the PLOS ONE Editors issue this Expression of Concern.
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190,000 in the US who got tested for vitamin D
then later got tested for COVID-19 by the same company
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Harvey W. Kaufman1, Justin K. Niles1, Martin H. Kroll1, Caixia Bi1, Michael F. Holick nD2 mfholick at bu.edu
1 Medical Informatics, Quest Diagnostics, Secaucus, NewJersey, United States of America,
2 Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude.
A total of 191,779 patients were included (median age, 54years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with “deficient”25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with “adequate” values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values >55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25 (OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV- 2 infection and COVID-19 disease.
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