Vitamin D Modulation in Respiratory Viral Infections

Vitamin D has emerged as a pivotal modulator of host defences against respiratory viruses, acting at the intersection of innate and adaptive immunity. The biologically active form, calcitriol, binds to the vitamin D receptor (VDR) in respiratory epithelial cells and immune cells, influencing gene transcription to enhance antimicrobial peptide production and regulate pro-inflammatory cytokine release. This dual action fortifies mucosal barriers and attenuates the excessive inflammation that underlies severe disease. Mechanistic studies reveal that vitamin D signalling upregulates cathelicidins and defensins, which impede viral replication, and tunes type I interferon responses to improve viral clearance without provoking tissue-damaging cytokine storms. Observational data link low serum 25-hydroxyvitamin D levels to increased susceptibility, higher viral loads and worse clinical outcomes in infections such as influenza and COVID-19. Interventional trials have further shown that regular, daily or weekly supplementation in deficient individuals reduces the incidence and severity of acute respiratory tract infections. The global burden of viral pneumonia and the seasonal ebb and flow of vitamin D status, particularly in higher latitudes, underscore the potential public health impact of optimizing vitamin D concentrations. Practical applications extend from prophylactic supplementation in at-risk populations to adjunctive therapy during active infection, while also informing vaccine responsiveness. Continued research aims to refine dosing regimens, identify responsive subgroups and integrate vitamin D modulation into comprehensive antiviral strategies.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Vitamin D Modulation in Respiratory Viral Infections publication trend

The graph below shows the total number of articles in vitamin d modulation in respiratory viral infections across all publications each year (not limited to Nature Index journals).

Technical terms

25-Hydroxyvitamin D (25(OH)D): The main circulating form of vitamin D used to assess an individual’s vitamin D status.

Calcifediol: A hydroxylated precursor to the active hormone calcitriol, often used in clinical supplementation.

Vitamin D receptor (VDR): A nuclear receptor that binds calcitriol and regulates gene transcription related to immune function.

Type I interferon: A group of cytokines critical for antiviral defence, promoting viral clearance and modulating inflammation.

Antimicrobial peptides: Small molecules such as cathelicidins and defensins that disrupt viral particles and infected cells.

References

1. Age-differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - Effects of vitamin D. Mucosal Immunology (2023).
2. Calcifediol boosts efficacy of ChAdOx1 nCoV-19 vaccine by upregulating genes promoting memory T cell responses. npj Vaccines (2024).
3. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. The BMJ (2017).
4. Modulation of the Immune Response to Respiratory Viruses by Vitamin D. Nutrients (2015).