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 versus D3 blood levels. Mortality rates from clinical studies were corrected for age, sex, and diabetes. Data were analyzed using correlation and linear regression. Results: One population study and seven clinical studies were identified, which reported D3 blood levels preinfection or on the day of hospital admission. The two independent datasets showed a negative Pearson correlation of D3 levels and mortality risk (r(17) = −0.4154, p = 0.0770/r(13) = −0.4886, p = 0.0646). 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) = −0.3989, p = 0.0194). Regression suggested a theoretical point of zero mortality at approximately 50 ng/mL D3. Conclusions: The datasets provide strong evidence that low D3 is a predictor rather than just 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.

Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes

“…However, either the large time frame between 25OHD measurement and the COVID-19 infection or the possible influence of confounding factors render the results of that study questionable ( 113 ). Nevertheless, beyond its plausible causal role, the presence of vitamin D deficiency/insufficiency at hospital admission should be considered as a relevant prognostic marker of disease severity in COVID-19 patients ( 114 ).…”

Dietary supplements intake during the second wave of COVID-19 pandemic: A multinational Middle Eastern study

“…In addition, vitamin D and B supplementations were thought to be associated with a decreased risk of mortality among severely infected COVID-19 patients [42] . However, although there is strong scientific evidence supporting the correlation between the mortality rate and severity of COVID-19 infection and blood levels of Vitamin D, still there is an open debate on the causal relationship [43] .…”

The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2

“…Vitamin D (Vit D) is an oxysterol hormone with important immunomodulatory and antiviral properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Even though this vitamin is often recommended as a nutritional supplement in treatment guidelines and prescribed for the management of coronavirus disease 2019 (COVID-19) [ 9 , 10 , 11 , 12 ], several studies have yielded divergent or inconclusive results [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”