J Clin Endocrinol Metab. 2021 Dec 11 doi: 10.1210/clinem/dgab892
Harsha Anuruddhika Dissanayake 1, Nipun Lakshitha de Silva 2, Manilka Sumanatilleke 3, Sawanawadu Dilantha Neomal de Silva 4, Kavinga Kalhari Kobawaka Gamage 3, Chinthana Dematapitiya 3, Daya Chandrani Kuruppu 5, Priyanga Ranasinghe 6, Sivatharshya Pathmanathan 3, Prasad Katulanda 1 7
Note: Defintion of "Low" Vitamin D varied: <10, <12. >15. <20, and <30. but was apparently ignored
Purpose: Vitamin D deficiency/insufficiency may increase the susceptibility to COVID-19. We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment.
Methods: We searched CINHAL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to 30.05.2021 for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4∙1∙0). Heterogeneity was determined by I 2 and sources were explored through pre-specified sensitivity analyses, subgroup analyses and meta-regressions.
Results: Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n=1,976,099).
Vitamin D deficiency/insufficiency increased the odds of developing
- COVID-19 (OR 1∙46, 95% CI 1∙28-1∙65, p<0∙0001, I 2=92%),
- Severe disease (OR 1∙90, 95% CI 1∙52-2∙38, p<0.0001, I 2=81%) and
- death (OR 2∙07, 95% CI 1∙28-3∙35, p=0.003, I 2=73%).
25-hydroxy vitamin D (25(OH)D) concentration were lower
- in individuals with COVID-19 compared to controls (mean difference [MD] -3∙85 ng/mL, 95% CI -5∙44,-2∙26, p=<0.0001),
- in patients with severe COVID-19 compared to controls with non-severe COVID19 (MD -4∙84 ng/mL, 95% CI -7∙32,-2∙35, p=0∙0001) and
- in non-survivors compared to survivors (MD -4∙80 ng/mL, 95%-CI -7∙89,-1∙71, p=0∙002).
The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19 and vitamin D deficiency/insufficiency partly explained the heterogeneity.
Four RCTs were widely heterogeneous precluding meta-analysis.
Conclusion: Multiple observational studies involving nearly two million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.
Download the PDF from VitaminDWiki
- Vitamin D fights COVID (54 studies of 1,400,000 people) – 23rd meta-analysis - Dec 2021
- COVID-19 treated by Vitamin D (reduce ICU by 3X) - 22nd meta-analysis - Dec 29, 2021
- COVID-19 death increased 2X if low Vitamin D (less than 10 to less than 30 ng) – 21st meta-analysis Dec 2021
- 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
- COVID-19 and Vitamin D (42 studies, consensus) – Oct 2021
- Overview of reviews of COVID-19 and vitamin D, etc. – April 2021
- Vitamin D can prevent severe COVID-19 in Latin America too – review Feb 1, 2021
- Many COVID-19 risks are associated with low vitamin D (7 studies) – Systematic Review Jan 2021
- Excellent on-going analysis of Vitamin D and COVID-19 publications not a formal publication
- COVID-19 Disease and Vitamin D: A Mini-Review – Dec 15, 2020
- 75 articles indicate that Vitamin D should fight COVID-19 – Evidence Review Dec 10, 2020
- 5.8 X more likely to die of COVID-19 if low vitamin D - Systematic Review Dec 3, 2020
- COVID-19 Scoping Review of Vitamin D finds lots of evidence, protocol to be used is unclear - Nov 26, 2020