ABSTRACT
Coronavirus Disease 2019 (COVID-19) poses an enormous challenge to health care systems throughout the world, but it doesn't affect every individual to the same extent. There is great variability in disease outcomes. Therefore, identifying the main prognostic risk factors is of paramount importance. These include increased age, skin pigmentation, obesity, pre-existing illness, and vitamin D deficiency. Vitamin D is a molecule with established effectiveness against various upper respiratory infections. This is due to its pivotal role as modulator of the innate and adaptative immune system through different mechanisms. Moreover, vitamin D can regulate the renin-angiotensin system that is exploited by SARS-CoV-2 for entry into the host cells. Vitamin D supplementation is thus a therapeutic option to consider, especially since it has low toxicity, and there are few currently available drugs for COVID-19 treatment. In this review chapter, we engage an immunological lens to discuss potential mechanisms by which vitamin D signaling might regulate COVID-19 disease susceptibility, severity, and by consequence, mortality. Hence, a critical analysis of the clinical trials published to date has been undertaken to address the value of vitamin D supplementation. We also discuss, based on plausible immunological mechanisms, the relationship between vitamin D and Long-COVID, as well as its effect on SARS-CoV-2 vaccination responsiveness. © 2023 Elsevier Inc. All rights reserved.