Evidence-Based Medicine
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. May 25, 2021; 10(3): 111-129
Published online May 25, 2021. doi: 10.5501/wjv.v10.i3.111
Association between population vitamin D status and SARS-CoV-2 related serious-critical illness and deaths: An ecological integrative approach
Dimitrios T Papadimitriou, Alexandros K Vassaras, Michael F Holick
Dimitrios T Papadimitriou, Pediatric - Adolescent Endocrinology and Diabetes, Athens Medical Center, Marousi 15125, Greece
Dimitrios T Papadimitriou, Endocrine Unit, Aretaieion University Hospital, Athens 11528, Greece
Alexandros K Vassaras, Neurology Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
Alexandros K Vassaras, Neuroimmunology Department, Democritus University of Thrace, Alexandroupoli 68100, Greece
Michael F Holick, Section Endocrinology, Nutrition and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA 02118, United States
Author contributions: All authors contributed to this manuscript; Papadimitriou DT and Vassaras AK contributed to conceptualization; Holick MF did data curation; Papadimitriou DT contributed to formal analysis and methodology; Holick MF contributed to project administration; Vassaras AK did visualization; Papadimitriou DT wrote the original draft; Holick MF wrote, reviewed and edited the manuscript; all authors have read and approve the final manuscript.
Conflict-of-interest statement: Holick MF was a former consultant for Quest Diagnostics, consultant for Ontometrics Inc. and speaker’s Bureau for Abbott Inc. The other authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The guidelines of the PRISMA 2009 Statement have been adopted.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dimitrios T Papadimitriou, MD, MSc, PhD, Director, Pediatric - Adolescent Endocrinology and Diabetes, Athens Medical Center, 58, Kifisias av., Marousi 15125, Greece. info@pedoendo.net
Received: January 10, 2021
Peer-review started: January 10, 2021
First decision: February 15, 2021
Revised: February 21, 2021
Accepted: April 7, 2021
Article in press: April 7, 2021
Published online: May 25, 2021
Processing time: 127 Days and 13.2 Hours
Abstract
BACKGROUND

Vitamin D population status may have possible unappreciated consequences to the coronavirus disease 2019 (COVID-19) pandemic. Α significant association between vitamin D sufficiency and reduction in clinical severity and inpatient mortality from COVID-19 disease has recently been shown, while a recent study has claimed lower COVID-19 cases in European countries with a better vitamin D status. Low serum 25-hydroxyvitamin-D [25(OH)D] was identified as an independent risk factor for COVID-19 infection and hospitalization, and administration of 0.532 mg (21280 IU) of calcifediol or 25(OH)D, followed by 0.266 mg on days 3 and 7 and then weekly until discharge or intensive care unit admission significantly reduced the need for intensive care unit treatment.

AIM

To elucidate the role of vitamin D European population status in the COVID-19 pandemic, data from the Worldometer were analyzed.

METHODS

Linear regression explored the correlation between published representative-standardized population vitamin D concentrations and the number of total cases/million (M), recovered/M, deaths/M and serious-critically ill/M from COVID-19 for 26 European countries populated > 4 M (Worldometer). Life expectancy was analyzed with semi-parametric regression. Weighted analysis of variance/analysis of covariance evaluated serious-critical/M and deaths/M by the vitamin D population status: Deficient < 50, insufficient: 50-62.5, mildly insufficient > 62.5-75 and sufficient > 75 nmol/L, while controlling for life expectancy for deaths/M. Statistical analyses were performed in XLSTAT LIFE SCIENCE and R (SemiPar Library).

RESULTS

Linear regression found no correlation between population vitamin D concentrations and the total cases-recovered/M, but negative correlations predicting a reduction of 47%-64%-80% in serious-critical illnesses/M and of 61%-82%-102.4% in deaths/M further enhanced when adapting for life expectancy by 133-177-221% if 25(OH)D concentrations reach 100-125-150 nmol/L, sustained on August 15, 2020, indicating a truthful association. Weighted analysis of variance was performed to evaluate serious-critical/M (r2 = 0.22) by the vitamin D population status and analysis of covariance the deaths/M (r2 = 0.629) controlling for life expectancy (r2 = 0.47). Serious-critical showed a decreasing trend (P < 0.001) from population status deficient (P < 0.001) to insufficient by 9.2% (P < 0.001), to mildly insufficient by 47.6% (P < 0.044) and to sufficient by 100% (reference, P < 0.001). For deaths/M the respective decreasing trend (P < 0.001) was 62.9% from deficient (P < 0.001) to insufficient (P < 0.001), 65.15% to mildly insufficient (P < 0.001) and 78.8% to sufficient (P = 0.041).

CONCLUSION

Achieving serum 25(OH)D 100-150 nmol/L (40-60 ng/mL) (upper tolerable daily doses followed by maintenance proposed doses not requiring medical supervision, Endocrine Society) may protect from serious-critical illness/death from COVID-19 disease.

Keywords: COVID-19; SARS-CoV-2; Vitamin D status; Vitamin D concentrations; 25-hydroxyvitamin-D; Immunity

Core Tip: To elucidate the role of vitamin D in the coronavirus disease 2019 (COVID-19) pandemic, we examined associations between published representative and standardized European population vitamin D data and the Worldometer COVID-19 data. Linear regression found no correlation between population vitamin D concentrations and the total cases-recovered/million (M), but negative correlations predicting a reduction of 47%-64%-80% in serious-critical illnesses/M and of 61%-82%-102.4% in deaths/M further enhanced when adapting for life expectancy by 133-177-221% if 25-hydroxyvitamin-D concentrations reach 100-125-150 nmol/L. Weighted analysis of variance/analysis of covariance showed a decreasing trend (P < 0.001) evaluating serious-critical/M (r2 = 0.22) and the deaths/M (r2 = 0.629) after controlling for life expectancy (r2 = 0.47), by vitamin D population status, respectively.