Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: -1.7 × 10^-4/person-day, 95%-CI: -3.0 × 10^-4 to -3.3 × 10^-5/person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: -1.3 × 10^-4/person-day, 95%-CI -2.5 × 10^-4 to -7.1 × 10^-6/person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: -4.2 × 10^-5/person-day, 95%-CI: -10.0 × 10^-5 to 1.5 × 10^-5/person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

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