Vitamin D and Covid-19

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Supplementation studies

Randomized

Supports link to vitamin D

  • A parallel pilot randomized open label trial of 76 patients in Spain found that the administration of calcifediol reduced ICU admission and mortality. Of the 50 patients treated with calcifediol. 13/26 patients in the control group required ICU care compared with 1 in the intervention group. A subsequent statistical analysis showed that decreased ICU admissions were not due to uneven distribution of comorbidities or other prognostic indicators, to imperfect blinding, or to chance, but were instead associated with the calcifediol intervention. (Castillo et all, August 2020)
  • A randomized, placebo controlled trial found that therapeutic, high-dose cholecalciferol supplementation led to SARS-CoV-2 RNA negative status in additional 41.7% of mildly symptomatic Covid patients (p<0.001) and was useful for viral SARS-CoV-2 RNA clearance.

Does not support vitamin D link

  • A randomized, placebo controlled trial of 240 patients found that a one-time supplementation of 200,000 IU of vitamin D, on average 10 days after symptom onset did not reduce the length of hospital stay in severe Covid-19 patients. The treatment was safe and well tolerated.

Non-Randomized

  • A small cohort trial found that just 16% of patients who received vitamin D, magnesium, and vitamin B12 required oxygen compared with 61.5% of the previous cohort who did not receive DBM supplementation. (Chuen Wen Tan, October 2020)
  • A retrospective study found that hospitalized patients who were treated with vitamin D were less likely to die than those who did not receive vitamin D. (Ling et all, October 2020)
  • A retrospective study found that French nursing home residents who had recently received a bolus dose of vitamin D were more likely to survive a Covid-19 infection than residents who had not recently received a supplement. 92% of the 57 people who received vitamin D survived, while 66% of the 9 people in the cooperator group survived. (Anweller et. al, October 2020)
  • A retrospective study found that regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly. (Anweller et. al, November 2020)

Covid severity associated with serum vitamin D levels

Pre-infection blood samples

Supports link to vitamin D

  1. A retrospective cohort study found that Chicago patients who were likely vitamin D deficient were more likely to test positive for Covid-19. (Meltzer et al, May 2020)
  2. An Israeli study of 7,000 patients with pre-Covid serum vitamin D tests found that vitamin D levels were associated with Covid infection and hospitalization. (Eugene Merzon et al, July 2020)
  3. An analysis of Israeli vitamin D tests performed between 2010 and 2019 found that vitamin D deficiency predicted Covid-19 infection. (Israel et al, August 2020)
  4. An analysis of 190,000 patients found that the probability of testing positive was associated with vitamin D levels. This association held across all age groups, ethnicities and geographies. (Kaufman et all, Sept 2020)

Does not support vitamin D link

  • Vitamin D levels between 2006-2010 were associated with Covid-19 mortality, but not after controlling for other variables in the data set. It’s hard to make inferences from 10 year old blood samples because there’s a causal story in which low vitamin D in 2010 increases vitamin D in 2020 because that group is likely to supplement. (Hastie et al, July 2020)

Post-infection blood samples

Supports vitamin D link

  1. A re-analysis of 107 Swiss blood samples found that PCR positive patients had 25-hydroxyvitamin D concentrations half that of PCR negatives. This finding held after stratifying for age and gender. (Avolio et 1) l, April 2020)
  2. Hospitalized male Covid-19 patients were found to have lower vitamin D levels than controls. (De Smet et al, May 2019)
  3. A observational study from Belgium found that vitamin D deficiency is correlated with the risk for hospitalization for COVID-19 pneumonia and predisposes to more advanced radiological disease stages. (De Smet, May 2020)
  4. Vitamin D deficiency was more common among ITU Covid patients than the general population in a Newcastle hospital. (Panagiotou et all, June 2020)
  5. A Mexican study found that patients with vitamin D serum levels bellow 8 ng/mL had 3.68 higher risk of dying from COVID-19. (Arturo Rodríguez Tort et al, April 2020)
  6. A Iranian study (Maghbooli et al, September 2020) found there was a significant association between vitamin D sufficiency and reduction in clinical severity. Note that an expression of concern was filed for this publication.
  7. A study of 42 COVID-19 patients in a respiratory ICU found that 50% of vitamin D deficient patients died after 10 days compared with 5% of non-deficient patients. (Carpagnano et all, August 2020)
  8. A prospective cohort study found that vitamin D deficiency was more common among Covid positive patients presenting with Covid symptoms than Covid negative patients, and suggested that it could be considered as a diagnostic tool. (Baktash V et all, August 2020)
  9. A study of patients presenting with Covid symptoms at an Iranian hospital found that vitamin D deficiency and ACE dysregulation were more common among those who tested positive for Covid-19. (Mardenia et all, August 2020)
  10. A German Study found that vitamin D status was associated with need for mechanical ventilation and death. (Radujkovic et al, August 2020)
  11. A small prospective cohort study of older adults found that vitamin D deficiency was associated with mechanical ventilation, but not death. (Baktash et all, September 2020)
  12. A Turkish study found that vitamin D deficiency was associated with mortality. (Karahan & Katkat October 2020)
  13. A study of UK health professionals found that vitamin D deficient individuals were more likely to be seropositive for Covid antibodies. (Aduragbemi et all, October 2020)
  14. A study of Covid positive children found that children with Covid had lower vitamin D levels than healthy controls. (Yilmaz & Sen, October 2020)
  15. A case control study in China found that vitamin D deficiency was higher in Covid patients than healthy controls, and that it was associated with disease severity. (Ye et. al, October, 2020)
  16. A retrospective case control study of 216 hospitalized patients found that 80% of Covid patients were vitamin D deficient, while just 42% of matched controls were deficient. The study did not find that vitamin D deficiency was associated with disease outcome. (Hernández et al, October 2020)
  17. A study of 74 hospitalized patients found that vitamin D deficiency was associated with Covid lung involvement, and mortality. (Abrishami et all, October 2020)
  18. A prospective observational study found that criticlaly ill Covid patients had higher rates of vitamin D deficiency than asymptomatic patients. (Jain et al, November 2020)

Does not support link to vitamin D

  1. A small trial did not find an association between vitamin D deficiency and Covid-19 severity. The study did find an association among younger patients. (Macaya et. al, September 2020)
  2. A case-control study did not find that Covid positive patients had lower vitamin D levels than patients hospitalized with non-Covid pneumonia or a set of non-respiratory conditions. The comparator groups in this study are a bit strange because low vitamin D levels are implicated in almost all of the diagnoses included in this study. See the comments associated with the paper. (Tomasti et al, October 2020)
  3. An Italian study of 347 patients did not find that hospitalized Covid patients had lower serum vitamin D than non-Covid patients. The authors note that “Because a large portion of patients were below the suggested 30 ng/mL threshold, we can’t exclude that VitD supplementation, restoring normal levels, might be beneficial in reducing the risk of infection.” (Ferrari & Locatelli, November 2020)
  4. A study of 135 hospitalized patients in the Netherlands was not assoicated with need for mechanical ventilation or death. The author’s note that vitamin K may be an important factor along with vitamin D. (Walk et al, November 2020)