johanf85 / vitamin_d_covid

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The argument for supplementation

  • Vitamin D reduces the risk of other acute respiratory infections. One interesting finding of this meta-analysis is that people who were very deficient (less than 25 nmol/L) saw the largest protective effect with an adjusted odd ratio of 0.58 and a 95% CI of 0.40 to 0.82. These are the same populations which seem to be at risk for severe Covid-19.
  • Calcitriol, the active form of Vitamin D is active against the SARS-COV2 virus.
  • A Mendelian randomisation analysis of excess COVID-19 mortality of African-Americans in the US suggests that vitamin D is a risk factor for Covid Mortality
  • Several studies have now observed lower vitamin D levels among severe Covid-19 patients
  • Vitamin D is very low risk an adverse events of vitamin D supplementation can be easily managed by clinicians

Direct research on vitamin D and Covid

Evidence of a causal link

In vitro evidence

  • Calcitriol, the active form of Vitamin D is active against the SARS-COV2 virus.

Covid severity associated with serum vitamin D levels

Post-infection blood samples

Supports vitamin D link

  • 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.
  • A restrospective study in the Philippines found a significant association between vitamin D status and severe Covid-19 infections.
  • Hospitalized male Covid-19 patients were found to have lower vitamin D levels than controls
  • 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.
  • Vitamin D deficiency was more common among ITU Covid patients than the general population in a Newcastle hospital.
  • 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.

Pre-infection blood samples

Supports link to vitamin D

  • A retrospective cohort study found that Chicago patients who were likely vitamin D deficient were more likely to test positive for Covid-19.
  • An Isreali study of 7,000 patients with pre-Covid serum vitamin D tests found that vitamin D levels were associated with Covid infection and hospitalization.

Contradicts 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.

Intervention studies

  • 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.

Ecological studies

  • A study out of Northwestern University found that the vitamin D status of a country's elderly population was associated with the number of severe cases of Covid-19 in that country.
  • There was a strong correlation between vitamin D levels and European mortality which increased over time.
  • UVB radiation, which the skin uses to manufacture vitamin D is associated with lower death rates and case fatality rates.
  • Covid-19 deaths-per-million appears to vary by latitude.
  • Latitude was not associated with a proportional increase in cases during one week of March.
  • Latitude is a significant predictor of Covid mortality after controlling for age.

Vitamin D background and previous studies

  • Vitamin D reduces the risk of other acute respiratory infections. One interesting finding of this meta-analysis is that people who were very deficient (less than 25 nmol/L) saw the largest protective effect with an adjusted odd ratio of 0.58 and a 95% CI of 0.40 to 0.82. These are the same populations which seem to be at risk for severe Covid-19.
  • Vitamin D and Influenza — Prevention or Therapy?
  • Vitamin D and the anti-viral state
  • Vitamin D Supplementation to Prevent Acute Respiratory Tract Infections: Systematic Review and Meta-Analysis of Individual Participant Data

Comprehensive debate by the Irish Medical Journal:

  • Covid-19, Cocooning, and Vitamin D Intake Requirements Link
  • Authors of Article ‘Optimisation of Vitamin D Status for Enhanced Immuno-Protection against Covid-19’ by McCartney et al. comment on response report‘Covid-19, Cocooning and Vitamin D Requirements’ by McKenna et al Link
  • Vitamin D and Inflammation: Potential Implications for Severity of Covid Link
  • Authors of Article ‘Optimisation of Vitamin D Status for Enhanced Immuno-Protection against Covid-19’by McCartney et al. comment onresponse letter ‘Vitamin D and Covid-19: A Note of Caution’ by Rabbitt et al.Link
  • Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection Link

Lit reviews and clinical guidance

  • This review of potential vitamin D mechanisms of action provides some useful history on the origin of vitamin D dosing recommendations. They also review their clinical guidelines after treating several thousand patients with 5000-10000 IU/day, including recognizing and resolving hypercalcemia or other adverse events.
  • Slovenia has begun administering vitamin D to residents of nursing homes and health care workers.
  • A review in Nature suggests that all patients should be monitored and potentially treated for vitamin D deficiency.
  • A bmj report which is generally critical of the connection between Covid-19 and vitamin D nevertheless concludes that supplementation according to government health guidelines (no more than 4,000 IU/day) is sensible for most people.
  • Evidence supports a vitamin-D causal model more than an acausal one.
  • A quarantine hospital in Egypt has started providing vitamin D to frontline medical workers.
  • The French National Academy of Medicine now recommends vitamin D supplementation as a preventative and adjuvent therapy for Covid-19 infection.
  • NICE, an English clinical research group, does not recommend vitamin D supplementation.
  • A review of the evidence finds that supplementing with vitamin D in accordance with government guidelines is a good idea, but there is no evidence to support supplementation rates higher than 4,000 IU/day

Vitamin D / Covid correlations

  • Vitamin D deficiency is very common in places that have been hit hard by the disease.
  • Vitamin D reduces the risk of thrombosis which is one of the puzzling symptoms of Covid-19
  • People with the genetic condition phenylketonuria tend to consume a diet fortified with vitamin D, and anecdotally have not suffered any Covid-19 deaths.
  • Hypocalcemia was associated with covid-19 severity. Vitamin D deficiency is one cause of hypocalcemia.

Race and Covid

  • Black and Asian populations are at a high risk of Covid morality. Some studies have found a relationship between skin pigmentation an vitamin D levels, but others have found that there is no difference in bio-available vitamin D because of differences in genetic polymorphisms related to vitamin D–binding protein. Interestingly, vitamin D binding protein is itself associated with infectious lung diseases.
  • There are lots of other factors which vary by race and which make Covid mortality more likely. These do not fully explain the race gap.
  • BAIPO, which represents UK doctors of Indian origin wrote to the NHS advocating for vitamin D testing and supplementation for front line staff. They are providing all members with vitamin D on request.
  • Black people are 5 Times More Likely to Develop COVID-19: Spatial Modeling of New York City ZIP Code-level Testing Results
  • Excess African-American mortality in the US was higher in southern states than northern states.
  • A dataset of 6 million US veterans found that Black and Hispanic had higher rates of Covid-19 which were not explained by medical conditions or where they live or receive care.
  • An analysis found that immigrants to Sweden from low and middle income countries were 1.5-2.5 times more likely to die from Covid.
  • An analysis of census data found that for all minorities, the minority's population share is strongly correlated with total COVID-19 deaths.

MIS-C, PIMS-TS, Kawasaki Disease

Supplementation in the absence of evidence

Potential Mechanisms

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