Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection
Authors: Mehdi Ebrahimi
Marzieh Pazoki
Mahnaz Montazeri
Mohammad Ali Sahraian
Azar Hadadi
Hedieh Moradi Tabriz
Samira Kafan
Michael F Holick
Arash Shirvani
Mehrad Nasiri
Zhila Maghbooli
Journal: PLoS ONE (2020)
Discipline: Multidisciplinary
Keywords: serum 25-hydroxyvitamin D levels; adverse clinical outcomes; immune function; mortality; SARS-CoV-2 infection
Affiliations: Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran., Endocrinology Department, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Department of Infectious Diseases, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Department of Internal Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Department of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Research Development Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Department of Medicine, Section of Endocrinology, Nutrition, Diabetes and Weight Management, Boston University Medical Center, Boston, Massachusetts, United States of America.

Abstract:  Background: To investigate the association between serum 25-hydroxyvitamin D levels and its effect on adverse clinical outcomes, and parameters of immune function and mortality due to a SARS-CoV-2 infection. Study design: The hospital data of 235 patients infected with COVID-19 were analyzed. Results: Based on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32.8% were vitamin D sufficient. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP) and an increase in lymphocyte percentage. Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D&lt; 30 ng/ml. The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection. Conclusion: Therefore, it is recommended that improving vitamin D status in the general population and in particular hospitalized patients has a potential benefit in reducing the severity of morbidities and mortality associated with acquiring COVID-19. 

Retracted: No

PubPeer comments:
 https: twitter.com GidMK status 1310726774657966080 , 
 https: twitter.com sTeamTraen status 1311067055660118017 , 
 In light of these concerns (#1 and #2), would the authors be able to make the anonymized data available for further analysis? , 
 The thread by me, incorporated in point #2, includes an earlier thread about a separate issue with the paper. I am posting that here for clarity. https: twitter.com sTeamTraen status 1310997416305451010?s=20 , 
 https: coronavirus.medium.com vitamin-d-and-covid-19-90f1d1493cc0 , 
 After this article [1] was published, concerns were raised about the validity of results and conclusions reported in the article and about undisclosed competing interests. Specifically, *Concerns were raised about the reported studyu2019s 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 articleu2019s 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 articleu2019s Competing Interests statement says, u201cThe authors have declared that no competing interests exist.u201d 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, u201cwe cannot explain the cause and effect relationship of vitamin D sufficiency and the reduced risk of severity from a COVID-19 infection.u201d [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. https: journals.plos.org plosone article?id=10.1371 journal.pone.0240965 h t [Retraction Watch] ,