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Brief overview: Current evidence suggests vitamin D replacement may reduce risk for acute respiratory tract infections (ARTI) in people with deficiency or insufficiency, although the effects of supplementation on incidence and severity of ARTI in the general population remain unknown. Oral vitamin D supplemzentation taken at routine doses appears to be generally safe and well tolerated. Verdict: Current experimental evidence remains inconclusive regarding the effects of vitamin D supplementation in the general population for the prevention and treatment of acute respiratory tract infections (ARTI). There is also insufficient evidence to draw conclusions regarding the impact of vitamin D supplementation on the severity or duration of ARTI, nor on outcomes related to lung injury or hospitalization from ARTI. Based on this rapid review, sources of significant heterogeneity in published clinical trials include: differences study populations, inconsistent assessment of serum status at baseline, dosing variability, varying routes of administration, and/or inconsistent definitions of outcome measures. Experimental evidence and observations in large cohorts are generally consistent that vitamin D deficiency (<50 nmol/L [<20 ng/mL]) and insufficiency (<75 nmol/L [<30 ng/mL]) of serum 25-hydroxycholecalciferol (25-OHD) concentration is associated with increased risk of ARTI, and supplementation for those with deficiency/insufficiency may lead to clinically meaningful reductions in the incidence of ARTI. In this rapid review, vitamin D was primarily administered as oral supplementation, and findings suggested significant differences in daily oral dosing compared to periodic bolus dosing. Based on the available experimental evidence, vitamin D supplementation appears to have a high margin of safety with very few adverse events reported in children or adults from a variety of dosing strategies. Future clinical trials on vitamin D should consider the sources of heterogeneity in the existing experimental research and design trials that account for baseline status, evaluate the potential for prevention and treatment in at risk populations, standardize dosing strategies, assess product quality, assess outcomes according to gold standard definitions/diagnostic methods, and delineate viral ARTI from other causes when possible. The available mechanistic evidence related to immunological requirements for adequate vitamin D, the availability of observational and experimental evidence suggestive of clinically meaningful benefits (especially in deficient/insufficient participants), and the high margin of safety, should make vitamin D a high priority for additional clinical research during the current COVID-19 pandemic.