Is there evidence to support a relationship between vitamin D and respiratory infections

including coronavirus disease 2019?

Submission Category
Infectious Disease
Purpose 100 85
Vitamin D deficiency affects over 1 billion people worldwide. The literature has shown that low
vitamin D levels may increase the risk, frequency and severity of respiratory tract infections.
Vitamin D functions as a hormone to facilitate innate immunity and aid in development of
antimicrobial peptides. The purpose of this study is to assess current literature describing the
effects of vitamin D deficiency on viral respiratory tract infections (RTIs) including coronavirus
disease 2019 (COVID-19) and explore possible immunomodulatory effects of the hormone to
prevent infection.
Methods 225 200
A literature search was conducted using PubMed to find studies evaluating the relationship
between vitamin D and RTIs including COVID-19. The search was limited to literature
published after January 1, 2000. Search terms included: vitamin D deficiency, COVID-19, and
viral respiratory tract infections. Recent data published by the World Health Organization and
John Hopkins University on COVID-19 were also reviewed. Reviewers also manually searched
reference lists to find appropriate articles. Literature was reviewed to assess patient age, sex,
initial vitamin D concentration, frequency of vitamin D supplementation, dosage of vitamin D
administered and geographical location. Literature was included if it was in English and included
supplemental vitamin D as an intervention or assessed the effects of vitamin D deficiency for
patients 18 years of age or older. Observational studies and randomized control trials were
included. A specific focus was to assess studies that explored the relationship between vitamin D
concentrations and outcomes of infection. Outcome measures included RTIs in patients
receiving vitamin D supplementation compared to placebo as well as mean vitamin D serum
concentration in patients with infections such as COVID-19. The National Academy of Sciences
guidelines describe vitamin D serum concentration of less than 30 nmol/L as deficient.
Results 200 200

A total of fourteen articles were selected evaluating 34,034 subjects that were 18 years of age or
older (n=2,166 in randomized control trials n=31,868 in observational studies). Vitamin D doses
ranged from 500-4,000 units daily. Seven randomized control trials evaluating vitamin D
supplementation and its relationship to RTIs were found. Three trials showed vitamin D had a
statistically significant benefit; four did not find favorable results. Three trials showed decreasing
frequency of upper RTIs and symptoms (16.5% vs 27.8%(p=0.042), 23.3% vs 26.7%(p=0.09),
10.8% vs 18.6%(p=0.04)). One trial evaluated recurrent infections. Vitamin D supplementation
reduced disease burden in patients with recurrent RTIs (202 vs 249 infectious score)
(p=0.04).Seven observational studies evaluating serum concentrations of vitamin D showed
favorable results. Three studies found a relationship between mean vitamin D serum
concentrations and frequency of positive COVID-19 cases. In addition, there was a negative
correlation between mean vitamin D concentrations and frequency of positive cases. Vitamin D
concentrations at greater to or equal to 38 ng/ml decreased the rate of viral respiratory infections
by 50%. Serum vitamin D concentrations have been shown to be inversely related to upper RTIs
(OR 1.36 95% CI 1.01–1.84 in <10ng/mL and 1.24 95% CI 1.07-1.43 for 10-<30ng/mL).

Conclusion 98
Randomized control trials and observational studies showed that vitamin D supplementation had
some beneficial effects. Evidence showed that the dose of vitamin D administration as well as
vitamin D deficiency affected the occurrence of RTIs. Additional randomized controlled studies
evaluating vitamin D effect on RTIs should aim to show how vitamin D supplementation in
vitamin D deficient populations may decrease the frequency of RTIs especially COVID-19
patients. For the over 1 billion people who are vitamin D deficient, supplementation may
decrease their chance of contracting RTIs like COVID-19 and improve their outcomes in the
event they become infected.