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

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.

Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives

“…Interestingly, vitamin D deficiency has been found to be an independent risk factor for the development of ARDS, its severity, and mortality. Notably, a bulk of recent studies have reported that vitamin D deficiency is associated with severe COVID-19 and a higher risk for progression to ARDS [ 163 ]. Interestingly, the biologic pathways involved in the pleiotropic actions of vitamin D intersect with the dysregulated mechanisms during COVID-19-related ARDS, providing some possible explanations behind this association.…”

COVID-19: Role of Nutrition and Supplementation

“…In the category of micronutrients, vitamin C [ 60 , 61 , 62 , 63 , 64 ] and the aforementioned vitamin D are included [ 48 , 56 , 65 , 66 , 67 , 68 ]. In an important recent review [ 69 ] the authors state that additional well-designed studies on the role of vitamin supplementations in order to prevent and/or treat COVID-19 infections should be mandatory. Indeed, considering the biological pathways, their dysregulation could be linked to COVID-19 outcomes: For these reasons, further investigation on vitamin C levels at the time of COVID-19 infection, during the infection, and after the infection is required to clarify their role as predictive biomarkers of disease severity.…”

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019

“…Indeed, folate levels were demonstrated to be positively correlated with vitamin D levels in several studies [ 39 , 40 ]. To date, much has been published regarding a possible association between vitamin D deficiency, COVID-19 infection, and disease severity [ 20 , 21 , 22 , 23 , 24 , 41 ]. Moreover, Annweiler et al demonstrated that vitamin D supplementation was associated with a higher survival rate and lower COVID-19 disease severity [ 42 ].…”

“…Gene expression for PCFT is influenced, among other transcription factors, by vitamin D [ 1 , 19 ]. As vitamin D deficiency was associated with a higher infection rate and poor outcomes in COVID-19 patients [ 20 , 21 , 22 , 23 , 24 ], we hypothesized that folate levels in COVID-19 patients would be decreased.…”