Friday, July 8, 2022

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

Blood calcidiol 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
  • This study was to collect further evidence on this topic.
  • One population study and seven clinical studies were identified, which reported D3 blood levels preinfection or on the day of hospital admission.

The SARS-CoV-2 pandemic causing acute respiratory distress syndrome (ARDS) has lasted for more than 18 months

  • It has created a major global health crisis due to the high number of patients requiring intensive care, and the high death rate
  • According to many scientists and medical professionals, we are far from the end of this disaster and hence must learn to coexist with the virus for several more years, perhaps decades
  • The effectiveness of vaccination is limited in time, especially with the current vaccines designed to trigger an immunological response against a single viral protein
  • We have already learned that even fully vaccinated people can be infected
  • Currently, most infections do not result in hospitalization, especially for young individuals without comorbidities
  • A return to normal life in the near future seems unlikely
  • Mask requirements as well as limitations of public life will likely accompany us for a long time if we are not able to establish additional methods that reduce virus dissemination

Search Strategy and Selection Criteria

  • Initially, a systematic literature review was performed to identify relevant COVID-19 studies
  • Included studies were observational cohort studies that grouped two or more cohorts by their vitamin D3 values and listed mortality rates for the respective cohorts
  • Titles and abstracts were screened, and full-text articles were further analyzed for eligibility

Data Analysis

  • Collected studies were divided into a population study and seven hospital studies
  • Mortality rates and D3 blood levels from studies on hospitalized COVID-19 patients were assembled in a separate dataset
  • The two datasets were combined, and the mortality rates of the hospital studies were scaled according to the mortality range of the population studies, resulting in a uniform list of patient cohorts

Results

  • Database and registry searches resulted in 563 and 66 records, respectively
  • Nonsystematic web searches accounted for 13 studies, from which an additional 31 references were assessed
  • After removal of 104 duplicates and initial screening, 44 studies remained
  • Four meta-studies, one comment, one retracted study, one report with unavailable data, one wrong topic report, and one Russian language record were excluded.
  • The remaining 35 studies were assessed in full text, 20 of which did not meet the eligibility criteria due to their study design or lack of quantitative mortality data.

The median vitamin D3 level across countries was 23.2 ng/mL (17.4-26.8 μg/mL)

  • A frequency distribution of vitamin D levels is shown in Figure 4.
  • The correlations shown in Table 3 suggest the sex/age distribution, diabetes, and the rigidity of public health measures as some of the causes for outliers within the Ahmad dataset.

Attempted corrections of the CMR values in the population study by Ahmad

  • The extracted data from seven hospital studies showed a median vitamin D3 level of 23.2 ng/mL.
  • These data are plotted after correction of patient characteristics and scaling in combination with the data points from Ahmad in Figure 5. The correlation results show a significant negative Pearson correlation.

Correlation of mortality and vitamin D blood levels for the respective datasets

  • Pearson correlation (Mortality~Vit D) r(17) = −0.4154, p = 0.0770
  • r(13) = -0.3989, p < 0.0194
  • Spearman correlation (Death~Vitamin D) rs = −1.4300, p= 0.0661, N = 19
  • N = 34
  • e.g. Pearson correlation for both groups was also found to be significant

Table 5: Intercept 192.6788 114.4156 140.2880

  • Coefficient −4.4408 −2.7654

Discussion

  • This study illustrates that, at a time when vaccination was not yet available, patients with sufficiently high D3 serum levels preceding the infection were highly unlikely to suffer a fatal outcome.
  • The lower threshold for healthy vitamin D levels should lie at approximately 125 nmol/L or 50 ng/mL 25(OH)D3, which would save most lives, reducing the impact even for patients with various comorbidities such as diabetes, obesity, and high blood pressure.

Limitations

  • The study does not question the vital role that vaccination will play in coping with the COVID-19 pandemic.

Conclusion

  • Vaccination alone cannot prevent all SARS-CoV-2 infections and dissemination of the virus.
  • It is important to combine vaccination with routine strengthening of the immune system of the whole population by vitamin D3 supplementation to consistently guarantee blood levels above 50 ng/mL (125 nmol/L).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541492/

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