Association Between Vitamin D and Novel SARS-CoV-2 Respiratory Dysfunction - A Scoping Review of Current Evidence and Its Implication for COVID-19 Pandemic.

Aida Santaolalla,Sheeba Irshad,Kerri Beckmann,Joyce Kibaru,Mieke Van Hemelrijck,Debra Josephs

doi:10.3389/fphys.2020.564387

Abstract

ObjectivesTo assess the association between vitamin D deficiency and increased morbidity/mortality with COVID-19 respiratory dysfunction.DesignScoping review.Data SourcesOvid MEDLINE (1946 to 24 of April 2020) and PubMed (2020 to 17 of September 2020).Eligibility Criteria for Selecting StudiesA search using the search terms: [(cholecalciferol or ergocalciferol or vitamin D2 or vitamin D3 or vitamin D or 25OHD) and (SARS-CoV-2 or coronavirus or COVID or betacoronavirus or MERS-CoV or SARS-CoV or respiratory infection or acute respiratory distress syndrome or ARDS)]m.p. was conducted on the 24/04/2020 (Search A) and 17/09/2020 (Search B).Results91 studies were identified as being concerned with Acute Respiratory Infection (ARI)/Acute Respiratory Distress Syndrome (ARDS) and vitamin D, and 25 publications specifically explored the role of vitamin D deficiency in the development and progression of SARS-CoV-2/COVID-19 related ARDS. Search “A” identified three main themes of indirect evidence supporting such an association. Consistent epidemiological evidence exists linking low vitamin D levels to increased risk and severity of respiratory tract infections. We also report on plausible biological processes supporting such an association; and present weaker evidence supporting the benefit of vitamin D supplementation in reducing the risk and severity of ARIs. Uncertainty remains about what constitutes an appropriate dosing regimen in relation to reducing risk/severity of ARI/ARDS. More recent evidence (Search B) provided new insights into some direct links between vitamin D and COVID-19; with a number of cohort and ecological studies supporting an association with PCR-positivity for SARS-CoV-2 and vitamin D deficiency. The exact efficacy of the vitamin D supplementation for prevention of, or as an adjunct treatment for COVID-19 remains to be determined; but a number of randomized control trials (RCTs) currently underway are actively investigating these potential benefits.ConclusionOur rapid review of literature supports the need for observational studies with COVID-19 infected populations to measure and assess vitamin D levels in relation to risk/severity and outcomes; alongside RCTs designed to evaluate the efficacy of supplementation both in preventive and therapeutic contexts. The overlap in the vitamin D associated biological pathways with the dysregulation reported to drive COVID-19 outcomes warrants further investigation.

Highlights

Vitamin D deficiency affects almost 50% of the population worldwide (Holick, 2007)
United Kingdom and United States data from critically ill patients with COVID-19 indicate that people from Black, Asian and minority ethnic (BAME) backgrounds are at Abbreviations: 25(OH)D, 25-hydroxy vitamin D; acute lower respiratory infections (ALRI), acute lower respiratory infection; ARI, acute respiratory infection; ARDS, acute respiratory distress syndrome; ALI, acute lung injury; ACEI ACEII, angiotensin-converting enzymes I and II; BAME, black, asian and minority ethnic backgrounds; randomized controlled trials (RCTs), Randomized Clinical Trials; RAS, renin-angiotensin system; RTI, respiratory tract infection; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
Given the rapid turnaround of COVID-19 related literature published following the first peak of the SARS-CoV-2 pandemic, we conduced a second search in PubMed, a bibliographic database that comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books, with the following search terms: [(cholecalciferol or ergocalciferol or vitamin D2

Summary

Introduction

Vitamin D deficiency affects almost 50% of the population worldwide (Holick, 2007). Its high prevalence is a important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population (Melamed et al, 2008). The potential consequences of vitamin D deficiency are wide ranging It plays a role in the development and progression of chronic diseases such as cardiovascular disease, bone health, autoimmunity, type-2 diabetes, cancer and depression. Countries that lie below 35 degrees North have relatively low mortality rates (e.g., 14.6% of patients in northern latitudes to 0.6% of patients in southern latitudes) (Rhodes et al, 2020) This discrepancy has been suggested to be a consequence of the high prevalence of elderly populations in European countries (Bureau, 2020); 35 degrees North is the latitude above which people do not receive sufficient sunlight to retain adequate vitamin D levels during winter, suggesting a possible role for vitamin D in determining outcomes from COVID-19 (Lips et al, 2019). United Kingdom and United States data from critically ill patients with COVID-19 indicate that people from Black, Asian and minority ethnic (BAME) backgrounds are at Abbreviations: 25(OH)D, 25-hydroxy vitamin D; ALRI, acute lower respiratory infection; ARI, acute respiratory infection; ARDS, acute respiratory distress syndrome; ALI, acute lung injury; ACEI ACEII, angiotensin-converting enzymes I and II; BAME, black, asian and minority ethnic backgrounds; RCTs, Randomized Clinical Trials; RAS, renin-angiotensin system; RTI, respiratory tract infection; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

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