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. 2023 Feb 25;54:459. doi: 10.1016/j.clnesp.2023.02.015

Re: Vitamin D deficiency predicts 30-day hospital mortality of adults with COVID-19

Ephrem Kirub 1
PMCID: PMC9984282  PMID: 36963895

Dear Editor,

COVID-19, since the onset of the pandemic almost three years back, cost lots of lives and left many with disability. There has been controversy surrounding the association of Vitamin D levels with poor COVID-19 outcomes. Vitamin D is said to contribute to higher mortality in COVID-19 patients [1]. This study tries to identify if it is true [2].

The authors tried to address a clearly focused issue which is the association between low serum vitamin D levels and severe COVID-19 outcomes. They conducted a cohort study that is suitable to address the association between the independent and dependent variables. Moreover, they objectively measured vitamin D levels and COVID-19 infection using validated tests: direct competitive chemiluminescence immunoassay [3] and real-time polymerase chain reaction (qPCR) [4]. In addition, they used Kaplan–Meier analysis to estimate the probability of survival and complemented it with cox proportional hazards regression models to provide an effect estimate. This allowed the authors to control the confounding factors they included.

The authors mentioned that they conducted a retrospective cohort design on the Methodology part. However, since the outcome of the study had not occurred when they started the study, it should have been corrected as a prospective cohort design. In addition, they stated in-person interviews were used to collect information on chronic comorbidities. However, the Charlson Comorbidity Index (CCI) should have been completed from the medical record of the patient for validity.

Another issue here is that they did not control for some risk factors for increased COVID-19 mortality, such as ethnicity and socioeconomic status. The sample size was very small, which makes it difficult to control for the unknown confounding factors. In addition, since it has low power, the authors should not extrapolate the result to a broader community. Furthermore, the effect of antibiotics, steroids, and anti-coagulant, although included in the demographic part, was not analyzed. Since the number of people treated with each specific treatment differs between patients with low vitamin D and normal Vitamin D levels, it should have been analyzed to avoid information bias.

Moreover, the adjusted Hazard ratio (aHR) in the study is 0.98 with a p-value of 0.02. Although this means that the finding is significant since the p-value is less than 0.05, the adjusted hazard ratio suggests the risk of death between the two Vitamin D groups is almost the same. As compared to other variables like Comorbidity (aHR = 2.15) and male sex (aHR = 1.16) have more effect on the mortality than Vitamin D level.

Overall, the results are affected by residual confounding factors, the study has low power to extrapolate the findings and therefore the conclusion they reached is flawed.

Funding

There was no funding for this manuscript.

Author

The author conducted critical appraisal of the study using the Critical Appraisal Skills Program toolkit.

Declaration of competing interest

The author declares that he has no competing/conflicting interests.

Acknowledgment

I would like to acknowledge Dr. P. Peter Wang for guiding me with his knowledge and skill in critical appraisal.

References

  • 1.Dror A.A., Morozov N., Daoud A., Namir Y., Yakir O., Shachar Y., et al. Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness. PLoS One. 2022;17(2) doi: 10.1371/journal.pone.0263069. https://pubmed.ncbi.nlm.nih.gov/15369717/ [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  • 2.Neves F.F., Pott-Junior H., Sousa Santos S.D., Cominetti M.R., de Melo Freire C.C., da Cunha A.F., et al. Vitamin D deficiency predicts 30-day hospital mortality of adults with COVID-19. Clinical Nutrition Espen. 2022;50:322–325. doi: 10.1016/j.clnesp.2022.05.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Han S., Qiu W., Zhang J., Bai Z., Tong X. Development of a chemiluminescence immunoassay for quantification of 25-hydroxyvitamin D in human serum. Journal of Analytical Methods in Chemistry 2019; 2020 doi: 10.1155/2020/9039270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Chung Y.S., Lee N.J., Woo S.H., Kim J.M., Kim H.M., Jo H.J., et al. Validation of real-time RT-PCR for detection of SARS-CoV-2 in the early stages of the COVID-19 outbreak in the Republic of Korea. Sci Rep. 2021;11:14817. doi: 10.1038/s41598-021-94196-3. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical Nutrition Espen are provided here courtesy of Elsevier

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