Summary The pleiotropic role of vitamin D has been explored over the past decades and there is compelling evidence for an epidemiological association between poor vitamin D status and a variety of diseases. While the potential anti‐viral effect of vitamin D has recently been described, the underlying mechanisms by which vitamin D deficiency could contribute to viral disease development remain poorly understood. The possible interactions between viral infections and vitamin D appear to be more complex than previously thought. Recent findings indicate a complex interplay between viral infections and vitamin D, including the induction of anti‐viral state, functional immunoregulatory features, interaction with cellular and viral factors, induction of autophagy and apoptosis, and genetic and epigenetic alterations. While crosstalk between vitamin D and intracellular signalling pathways may provide an essential modulatory effect on viral gene transcription, the immunomodulatory effect of vitamin D on viral infections appears to be transient. The interplay between viral infections and vitamin D remains an intriguing concept, and the global imprint that vitamin D can have on the immune signature in the context of viral infections is an area of growing interest.

Summary Evidence suggests that vitamin D supplementation could potentially be effective either in treatment or prevention of coronavirus disease 2019 (Covid‐19). Indeed, several studies and trials have begun to investigate the impact of vitamin D supplementation on patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. In this review, we focus on the potential mechanisms of vitamin D in the pathogenesis of Covid‐19. We consider whether deficiency of vitamin D may be one of the underlying biological factors that could explain the excess mortality seen among non‐Caucasians. We also raise several important questions which need to be addressed to provide a clear picture of the extent to which vitamin D supplementation may benefit patients with Covid‐19, particularly those with underlying risk factors.

Background-Common variable immunodeficiency is the most common primary immunodeficiency. A subset of patients suffers from debilitating inflammatory complications.