COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis

Abstract

Background Much research shows that blood calcidiol (25(OH)D3) levels correlate strongly with SARS-CoV-2 infection severity. There is open discussion regarding whether low D3 is caused by the infection or if deficiency negatively affects immune defense. The aim of this study was to collect further evidence on this topic. Methods Systematic literature search was performed to identify retrospective cohort as well as clinical studies on COVID-19 mortality rates vs. D3 blood levels. Mortality rates from clinical studies were corrected for age, sex and diabetes. Data was analyzed using correlation and linear regression. Results One population study and seven clinical studies were identified, which reported D3 blood levels pre-infection or on the day of hospital admission. They independently showed a negative Pearson correlation of D3 levels and mortality risk (r(17)=-.4154, p=.0770/r(13)=-.4886, p=.0646). For the combined data, median (IQR) D3 levels were 23.2 ng/ml (17.4 – 26.8), and a significant Pearson correlation was observed (r(32)=-.3989, p=.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/ml D3. Conclusions The two datasets provide strong evidence that low D3 is a predictor rather than a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/ml to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity.

Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial

“…Several studies conducted earlier in the pandemic have linked vitamin D deficiency with the risk and severity of COVID-19 infection and hospitalization [26,27], while a recent systematic review and meta-analysis of eight studies and >1500 participants concluded that vitamin D levels over 50 nmol/L can reduce the mortality risk of COVID-19 to zero [28].…”

Vitamin D: A Potential Mitigation Tool for the Endemic Stage of the COVID-19 Pandemic?

“…Additionally, a meta-analysis showed a strong correlation between death rate caused by SARS-CoV-2 and vitamin D blood levels, reporting that a threshold level of 30 ng/mL decreased mortality considerably (103). A multicenter study measured [25(OH)D 3 ] in patients that had acute COVID-19, patients that had healed from COVID-19 and noninfected patients; the study showed that acute COVID-19 patients had the lowest levels of [25(OH)D 3 ] (9,63 ± 8.70 ng/mL), followed by healed patients (11.52 ± 4.90 ng/mL, p>0.05), with the highest levels reported by non-infected patients (15.96 ± 5.99 ng/mL, p = 0.0091) (104). The most recent systematic review and meta-analysis which involves approximately two million adults suggests that vitamin D insufficiency/deficiency increases susceptibility to COVID-19 and to severe COVID-19, with association regarding mortality reported as less robust (105).…”

Fall 2021 Update

“…Having adequate micronutrients like zinc and vitamins C and D can help our immune systems function better. For example, a not yet peer-reviewed systematic literature review released September 25, 2021, found that low blood levels of Vitamin D3 were a predictor of COVID-19 infection and mortality ( Borsche et al, 2021 ).…”