Vitamin D Deficiency Is Associated With Higher Hospitalization Risk From COVID-19

A Retrospective Case-Control Study

Edward B. Jude; Stephanie F. Ling; Rebecca Allcock; Beverly X. Y. Yeap; Joseph M. Pappachan

Disclosures

J Clin Endocrinol Metab. 2021;106(11):e4708-e4715. 

In This Article

Abstract and Introduction

Abstract

Context: One risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is postulated to be vitamin D deficiency. To better understand the role of vitamin D deficiency in the disease course of COVID-19, we undertook a retrospective case-control study in North West England.

Objective: To examine whether hospitalization with COVID-19 is more prevalent in individuals with lower vitamin D levels.

Methods: The study included individuals with test results for serum 25-hydroxyvitamin D (25[OH]D) between April 1, 2020, and January 29, 2021, from 2 districts in North West England. The last 25(OH)D level in the previous 12 months was categorized as "deficient" if less than 25 nmol/L and "insufficient" if 25 to 50 nmol/L.

Results: The study included 80 670 participants. Of these, 1808 were admitted to the hospital with COVID-19, of whom 670 died. In a primary cohort, median serum 25(OH)D in nonhospitalized participants with COVID-19 was 50.0 nmol/L (interquartile range [IQR], 34.0–66.7) vs 35.0 nmol/L (IQR, 21.0–57.0) in those admitted with COVID-19 (P < 0.005). In a validation cohort, median serum 25(OH)D was 47.1 nmol/L (IQR, 31.8–64.7) in nonhospitalized vs 33.0 nmol/L (IQR, 19.4–54.1) in hospitalized patients. Age-, sex-, and season-adjusted odds ratios for hospital admission were 2.3 to 2.4 times higher among participants with serum 25(OH)D <50 nmol/L compared with those with normal serum 25(OH)D levels, without excess mortality risk.

Conclusion: Vitamin D deficiency is associated with higher risk of COVID-19 hospitalization. Widespread measurement of serum 25(OH)D and treatment of insufficiency or deficiency may reduce this risk.

Introduction

Vitamin D deficiency has been proposed as a risk factor for many viral respiratory illnesses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite attempts to curtail coronavirus disease 2019 (COVID-19) resulting from SARS-CoV-2 infection, there has been only limited success, even after 18 months since the beginning of the mega-pandemic in December 2019.

Vitamin D has been thought to possess immunomodulatory functions, apart from its well-known effects on bone mineral metabolism.

Several observational studies[1–10] have examined the role of vitamin D on COVID-19 infection risk or disease outcomes with conflicting results. Although with some technical flaws and discrepancies in the assessment methods, 3 systematic reviews also assessed the risk of COVID-19 and vitamin D levels, and the benefits of supplementation on morbidity and mortality reduction from the disease.[11–13] These reviews suggested an overall increased risk of hospitalization (odds ratio [OR] 1.43–1.81) and mortality (OR 1.82; 95% CI, 1.6–2.58) from COVID-19 in patients with vitamin D deficiency. However, the studies included in these systematic reviews exhibited a high risk of various biases, such as inadequate evaluation of the outcome, inappropriate sample selection, and lack of uniformity of the inclusion criteria, and so the certainty of evidence emerging from these studies appears low. On the contrary, a study from Italy[14] and another from Brazil[15] clearly refute the probability of a causal link between vitamin D deficiency and susceptibility to SARS-CoV-2 infection. Therefore, it is imperative to have more evidence based on large population-based studies to reveal the risk of COVID-19 in populations with vitamin D deficiency, and multicenter randomized controlled trials to observe the potential benefits of vitamin D supplementation in treating the disease.

Most studies that have looked at prevailing vitamin D levels and COVID-19 have been performed in a small number of patients. Therefore, we set out to understand the role of vitamin D levels and the risk of developing COVID-19 in a large-cohort observational study from 2 hospital sites in North West England in the United Kingdom to uncover the uncertainties around this highly debated topic. Our primary outcome was to determine whether insufficient or deficient vitamin D status was associated with increased risk of hospitalization from COVID-19, with due consideration of Northern hemisphere's seasonal variations of vitamin D. Our secondary outcome was to determine whether insufficient or deficient vitamin D status was associated with increased risk of inpatient death from COVID-19.

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