Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis
EClinicalMedicine. 2021 Jul;37:100967. doi: 10.1016/j.eclinm.2021.100967
Andrea Crafa 1, Rossella Cannarella 1, Rosita A Condorelli 1, Laura M Mongioì 1, Federica Barbagallo 1, Antonio Aversa 2, Sandro La Vignera 1, Aldo E Calogero 1
Low vitamin D = < 20 ng
Note: several of the high studies were fradulent, so VitaminDWiki reduced the HR from 4.58 to 3.5
- COVID-19 risk reduced by vitamin D supplementation – umbrella review of 7 meta-analysis – Oct 2021
- COVID-19 treated by Vitamin D (example: ICU reduced by 5X) – 20th meta-analysis Oct 13, 2021
- Severe COVID-19 2.5 X more likely if low vitamin D (23 studies) – 19th meta-analysis Oct 2021
- COVID-19 mortality extrapolates to zero at 50 ng of vitamin D – 18th Meta-analysis Sept 2021
- COVID-19 death 1.6 X more likely if low vitamin D (24 studies) – 17th meta-analysis Aug 2021
- Severe COVID-19 5X more likely if low vitamin D (23 studies) – 16th meta-analysis July 2021
- Severe COVID-19 3.5 more likely if low vitamin D (30 studies) – meta-analysis July 2021
- COVID-19 patients who had supplemented with Vitamin D were 3X less likely to enter ICU – June 2021
- Low Calcium associated with severe COVID-19 – several studies
- COVID-19 mortality 3X more likely if low vitamin D (999,179 people) – meta-analysis March 29, 2021
- COVID-19 was 2.6X more severe if very low Vitamin D (43 studies) – meta-analysis March 26, 2021
- Low Vitamin D associated with 2.7X more severe COVID-19 – 12th MA March 5, 2021
- Vitamin D supplementation fights COVID-19 – 11th meta-analysis Jan 24, 2021
- 3.7 X less likely to die of COVID-19 if supplemented with Vitamin D - meta-analysis Jan 5, 2021
- Less likely to test positive for COVID-19 if higher Vitamin D – meta-analysis Jan 6, 2021
- Vitamin D reduces COVID-19 by 80 percent - anonymous meta-analysis - Jan 5, 2021
- COVID-19 1.7X more likely to be severe if low Vitamin D - meta-analysis Oct 2020
- Low Vitamin D associated 1.8X increased risk of COVID-19 death in hospital – meta-analysis Nov 4, 2020
- Acute viral respiratory infections (RTI) reduced by Vitamin D - 20 reviews - Aug 2020
- Prudent to consider that Vitamin D has a role in COVID-19 – meta-analysis – Aug 7, 2020
- Risk of enveloped virus infection is increased 50 percent if poor Vitamin D Receptor - meta-analysis Dec 2018
- Hepatitis B patients have 2 ng lower level of Vitamin D – meta-analysis June 2019
- Influenza Vaccination not benefited by lowish levels of vitamin D – meta-analysis March 2018
- As of Dec 2, 2021, the VitaminDWiki page had: 34 trials, 6 trial results, 28 meta-analyses and reviews, 64 observations, 36 recommendations, 55 associations, 89 speculations, 52 videos see related: Governments, HealthProblems, Hospitals, Dark Skins, 26 risk factors are ALL associated with low Vit D, Recent Virus pages Fight COVID-19 with 50K Vit D weekly Vaccines
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19.
Methods: Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: "Vitamin D", "25 hydroxy Vitamin D", "25 hydroxycholecalciferol", "cholecalciferol", "COVID 19″, "SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25-hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D <20 ng/ml, were also included. We calculated the mean difference (MD) and the 95% confidence intervals (CI) for quantitative variables such as 25(OH)D levels in patients with or without SARS-CoV-2 infection, in those with mild vs. severe COVID-19, or those who have died vs. those who have been discharged. Instead, we calculated odds ratios and 95% CI for qualitative ones, such as the number of patients with severe illness/death in the presence of VDD vs. those with normal serum 25(OH)D levels. A p-value lower than 0.05 was considered statistically significant. The study was registered on PROSPERO (CRD42021241473).
Findings: Out of 662 records, 30 articles met inclusion criteria and, therefore, were included in the meta-analysis. We found that the serum levels of 25(OH)D were significantly lower in patients with SARS-CoV-2 infection than in negative ones [MD -3.99 (-5.34, -2.64); p <0.00001; I2= 95%]. Furthermore, its levels were significantly lower in patients with severe disease [MD -6.88 (-9.74, -4.03); p <0.00001; I2=98%] and in those who died of COVID-19 [MD -8.01 (-12.50, -3.51); p = 0.0005; I2=86%].
Finally, patients with VDD had an increased risk of developing severe disease [OR 4.58 (2.24, 9.35); p <0.0001; I2=84%] but not a fatal outcome [OR 4.92 (0.83, 29.31); p = 0.08; I2=94%].
Interpretation: This meta-analysis revealed a large heterogeneity of the studies included due to the different enrolment criteria of patient samples (age, body mass index, ethnicity, comorbidities), the country where they live, all factors influencing serum 25(OH)D levels, and the different criteria used to define the severity of COVID-19. Furthermore, the observational nature of these studies does not allow to establish a cause-effect relationship, even taking into account that 25(OH)D represents a marker of acute inflammation. Treatment with vitamin D might be considered for the primary prevention of SARS-CoV-2 infection and the management of patients with COVID-19. However, further intervention studies are needed to prove this hypothesis.