The link between vitamin D deficiency and Covid-19 in a large population

Israel, Ariel; Cicurel, Assi; Feldhamer, Ilan; Dror, Yosef; Giveon, Shmuel; Gillis, David; Strich, David; Lavie, Gil

doi:10.1101/2020.09.04.20188268

Cited by 32 publications

(38 citation statements)

References 21 publications

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“…A population-based study among 4.6 million members of a Health Services provider in Israel showed that vitamin D levels estimated between 2010 and 2019 correlated strongly with COVID-19 incidence [ 60 ]. They found that vitamin D deficiency (less than 50 nmol l −1 ), and particularly severe vitamin D deficiency (less than 30 nmol l −1 ) was much more prevalent among Ultra-orthodox and Arabs.…”

Section: Preliminary Evidence Of Associations Between Vitamin D Statumentioning

confidence: 99%

Vitamin D and COVID-19: evidence and recommendations for supplementation

et al. 2020

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Vitamin D is a hormone that acts on many genes expressed by immune cells. Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable—links with ethnicity, obesity, institutionalization; latitude and ultraviolet exposure; increased lung damage in experimental models; associations with COVID-19 severity in hospitalized patients. Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol l −1 , as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021—although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800–1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU–1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain.

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Section: Preliminary Evidence Of Associations Between Vitamin D Statumentioning

confidence: 99%

Vitamin D and COVID-19: evidence and recommendations for supplementation

et al. 2020

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“…Israel et al performed a large multiethnic population-based study and found a highly significant correlation between prevalence of vitamin D deficiency and incidence of confirmed SARS-CoV-2 infections [7]. Influence of vitamin D status on COVID-19-related hospital admissions, ICU admissions and mortality were not assessed in this study [7].…”

Section: Observational Studiesmentioning

confidence: 70%

“…Data from observational and intervention studies on the effect of vitamin D status and vitamin D administration during COVID-19 are conflicting. In general, larger studies of higher quality demonstrate effects on disease susceptibility [7] but not on severity or disease outcome [3,9]. Vitamin D supplementation is generally considered to be safe [22], however, this may not always be the case [19].…”

Section: Resultsmentioning

confidence: 99%

“…Whereas Walk et al did not find differences in vitamin D status between hospitalized COVID-19 patients with poor and good disease outcomes [5], Jain et al demonstrated a strong association between vitamin D deficiency and COVID-19-related mortality [6]. Israel et al performed a large multiethnic population-based study and found a highly significant correlation between prevalence of vitamin D deficiency and incidence of confirmed SARS-CoV-2 infections [7]. Influence of vitamin D status on COVID-19-related hospital admissions, ICU admissions and mortality were not assessed in this study [7].…”

Section: Observational Studiesmentioning

confidence: 99%

“…Alternatively, vitamin D droplets -rather than tablets -might be used to bypass the endothelium. Israel et al demonstrated a protective effect from liquid vitamin D formulations against SARS-CoV-2 infections (OR 0.9) in a large population-based study, whereas use of vitamin D tablets was associated with increased risk (OR 1.2) [7]. A possible explanation might be that a significant proportion of vitamin D droplets is probably directly absorbed by the epithelial cells of the oropharynx and does not have to pass endothelial cells.…”

Section: Airway Epitheliummentioning

confidence: 99%

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Why Appreciation of Pulmonary Vitamin D Metabolism Should Temper Expectations for Vitamin D Supplementation to Reduce Disease Severity and Improve Clinical Outcome of COVID-19

Janssen¹,

Walk²,

Ouweland³

2020

Preprint

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Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

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Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results

et al. 2021

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IMPORTANCE Deficient (ie, <20 ng/mL) or insufficient (ie, 20 to <30 ng/mL) 25-hydroxyvitamin D (also known as calcifediol) levels are more common in Black individuals than White individuals and are associated with increased coronavirus disease 2019 (COVID-19) risk. Whether COVID-19 risk is associated with differences in vitamin D levels of 30 ng/mL or greater is not known. OBJECTIVE To examine whether COVID-19 test results are associated with differences in vitamin D levels of 30 ng/mL or greater, including for White individuals and for Black individuals. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study was conducted at an academic medical center in Chicago, Illinois. Participants included individuals with data on vitamin D

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The link between vitamin D deficiency and Covid-19 in a large population

Cited by 32 publications

References 21 publications

Vitamin D and COVID-19: evidence and recommendations for supplementation

Vitamin D and COVID-19: evidence and recommendations for supplementation

Why Appreciation of Pulmonary Vitamin D Metabolism Should Temper Expectations for Vitamin D Supplementation to Reduce Disease Severity and Improve Clinical Outcome of COVID-19

Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results

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