Vitamin D and coronavirus disease 2019 (COVID-19): rapid evidence review

Abstract

Background The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has re-ignited interest in the possible role of vitamin D in modulation of host responses to respiratory pathogens. Indeed, vitamin D supplementation has been proposed as a potential preventative or therapeutic strategy. Recommendations for any intervention, particularly in the context of a potentially fatal pandemic infection, should be strictly based on clinically informed appraisal of the evidence base. In this narrative review, we examine current evidence relating to vitamin D and COVID-19 and consider the most appropriate practical recommendations. Observations Although there are a growing number of studies investigating the links between vitamin D and COVID-19, they are mostly small and observational with high risk of bias, residual confounding, and reverse causality. Extrapolation of molecular actions of 1,25(OH)2-vitamin D to an effect of increased 25(OH)-vitamin D as a result of vitamin D supplementation is generally unfounded, as is the automatic conclusion of causal mechanisms from observational studies linking low 25(OH)-vitamin D to incident disease. Efficacy is ideally demonstrated in the context of adequately powered randomised intervention studies, although such approaches may not always be feasible. Conclusions At present, evidence to support vitamin D supplementation for the prevention or treatment of COVID-19 is inconclusive. In the absence of any further compelling data, adherence to existing national guidance on vitamin D supplementation to prevent vitamin D deficiency, predicated principally on maintaining musculoskeletal health, appears appropriate.

Vitamin D and COVID-19 disease: don’t believe everything you read in the papers! Reply to Dr William B. Grant

“…Definitive randomised controlled trials are lacking and the one well-conducted trial undertaken to date has shown no effect, albeit in a relatively small population [ 9 ]. We do not view the evidence base as conclusive one way or the other—the underlying biology, in terms of 1,25(OH) 2 D, as Dr Grant suggests, and as we documented in our review, would be compatible with an effect of vitamin D on COVID-19 [ 2 ]. Additionally, a large meta-analysis of supplementation for reduction in (non-COVID-19) respiratory infections also supports the possibility of an effect on this outcome [ 10 ].…”

“…We read with interest the letter [ 1 ] from William B Grant, director of the Sunlight, Nutrition and Health Research Centre, San Francisco, commenting on our narrative review of the evidence around vitamin D and COVID-19 disease [ 2 ]. Dr Grant suggests that confounding and reverse causality, at least as addressed in studies to date, do not account for associations between vitamin D and COVID-19 disease, where these have been observed.…”

“…In our review [ 2 ], we attempted to critically appraise the source studies available rather than simply report, or indeed synthesise, their results. It is clear from the characteristics of the component studies in Kazemi et al’s analysis that they are highly heterogeneous in terms of setting, design and methodology, generally of small sample size and also highly variable in ability to account for confounding and bias [ 4 ].…”

Vitamin D—let common sense prevail—on the balance of probabilities

“…High latitude, dark skin type, overweight, inflammatory conditions, are all predisposing factors for severe vitamin D deficiency (serum 25(OH)D below 25 nmol/l) [ 1 ]. The authors of the latest rapid evidence review for vitamin D and Covid-19 [ 2 ] find the evidence not compelling enough to advise population-wide prophylactic vitamin D supplementation to prevent Covid-19 severity. They confirm, however, vitamin D’s role in immune modulatory processes.…”

Vitamin D and coronavirus disease 2019 (COVID-19)—rapid evidence review

“…The recent review by Raisi-Estabragh and colleagues [ 1 ] concluded that evidence to support vitamin D supplementation for the prevention or treatment of COVID-19 is inconclusive. The main reasons given for reaching this conclusion were confounding considerations and reverse causation in observational studies, and limited data from intervention studies.…”