Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness
Dror et al.
, Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness
, PLOS ONE, doi:10.1371/journal.pone.0263069 (date from earlier preprint)
Retrospective 253 hospitalized patients in Israel showing higher mortality and higher risk of severe cases with vitamin D deficiency. Vitamin D levels were measured 14 to 730 days before the COVID-19 test. Adjusted results are only provided for severity.
risk of severe or critical case, 84.8% lower, RR 0.15, p = 0.001, high D levels 109 of 120 (90.8%), low D levels 76 of 133 (57.1%), adjusted per study, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk, >40ng/mL vs. <20ng/mL, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Dror et al., 7 Jun 2021, retrospective, Israel, peer-reviewed, 18 authors.
Abstract: PLOS ONE
Pre-infection 25-hydroxyvitamin D3 levels and
association with severity of COVID-19 illness
Amiel A. Dror ID1,2*, Nicole Morozov ID3, Amani Daoud1,2, Yoav Namir2, Orly Yakir4,
Yair Shachar1, Mark Lifshitz5, Ella Segal1,2, Lior Fisher1,2, Matti Mizrachi1,2,
Netanel Eisenbach1,2, Doaa Rayan1,2, Maayan Gruber1,2, Amir Bashkin2,6,
Edward Kaykov2,7, Masad Barhoum8, Michael Edelstein2, Eyal Sela1,2
1 Department of Otolaryngology, Head and Neck Surgery, Galilee Medical Center, Nahariya, Israel, 2 Azrieli
Faculty of Medicine, Bar-Ilan University, Safed, Israel, 3 Sackler Faculty of Medicine, Tel Aviv University, Tel
Aviv, Israel, 4 Statistical Analysis Division, Galilee Medical Center, Nahariya, Israel, 5 Computer Data
Division, Galilee Medical Center, Nahariya, Israel, 6 Endocrinology Unit, Galilee Medical Center, Nahariya,
Israel, 7 Geriatric Medicine Department, Galilee Medical Center, Nahariya, Israel, 8 Galilee Medical Center,
Citation: Dror AA, Morozov N, Daoud A, Namir Y,
Yakir O, Shachar Y, et al. (2022) Pre-infection 25hydroxyvitamin D3 levels and association with
severity of COVID-19 illness. PLoS ONE 17(2):
Editor: Dong-Yan Jin, University of Hong Kong,
Received: June 27, 2021
Accepted: January 12, 2022
Published: February 3, 2022
Copyright: © 2022 Dror et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Data Availability Statement: All relevant data are
within the manuscript and its Supporting
Funding: The author(s) received no specific
funding for this work.
Competing interests: The authors have declared
that no competing interests exist.
Studies have demonstrated a potential correlation between low vitamin D status and both
an increased risk of infection with SARS-CoV-2 and poorer clinical outcomes. This retrospective study examines if, and to what degree, a relationship exists between pre-infection
serum 25-hydroxyvitamin D (25(OH)D) level and disease severity and mortality due to
The records of individuals admitted between April 7th, 2020 and February 4th, 2021 to the
Galilee Medical Center (GMC) in Nahariya, Israel, with positive polymerase chain reaction
(PCR) tests for SARS-CoV-2 (COVID-19) were searched for historical 25(OH)D levels measured 14 to 730 days prior to the positive PCR test.
Patients admitted to GMC with COVID-19 were categorized according to disease severity
and level of 25(OH)D. An association between pre-infection 25(OH)D levels, divided
between four categories (deficient, insufficient, adequate, and high-normal), and COVID-19
severity was ascertained utilizing a multivariable regression analysis. To isolate the possible
influence of the sinusoidal pattern of seasonal 25(OH)D changes throughout the year, a
cosinor model was used.
Of 1176 patients admitted, 253 had records of a 25(OH)D level prior to COVID-19 infection.
A lower vitamin D status was more common in patients with the severe or critical disease
(<20 ng/mL [87.4%]) than in individuals with mild or moderate disease (<20 ng/mL [34.3%] p
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