Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity

Abstract

Vitamin D deficiency co-exists in patients with COVID-19. At this time, dark skin color, increased age, the presence of pre-existing illnesses and vitamin D deficiency are features of severe COVID disease. Of these, only vitamin D deficiency is modifiable. Through its interactions with a multitude of cells, vitamin D may have several ways to reduce the risk of acute respiratory tract infections and COVID-19: reducing the survival and replication of viruses, reducing risk of inflammatory cytokine production, increasing angiotensin-converting enzyme 2 concentrations, and maintaining endothelial integrity. Fourteen observational studies offer evidence that serum 25-hydroxyvitamin D concentrations are inversely correlated with the incidence or severity of COVID-19. The evidence to date generally satisfies Hill's criteria for causality in a biological system, namely, strength of association, consistency, temporality, biological gradient, plausibility (e.g., mechanisms), and coherence, although experimental verification is lacking. Thus, the evidence seems strong enough that people and physicians can use or recommend vitamin D supplements to prevent or treat COVID-19 in light of their safety and wide therapeutic window. In view of public health policy, however, results of large-scale vitamin D randomized controlled trials are required and are currently in progress.

Keywords: 25-hydroxyvitamin D; COVID-19; IL-6; MMP-9; SARS-CoV-2; cathelicidin; endothelial dysfunction; immune system; inflammation; vitamin D.

Figure 1

The cascade of events by the innate immune system in response to viral infections. Among the functions of AMPs (antimicrobial peptides) is chemotaxis, the movement of cells in response to a chemical stimulus, here macrophages, mast cells, monocytes, and neutrophils. Other effects include activation of the innate immune system, effects on angiogenesis, antiendotoxin activity, and opsonization (the molecular mechanism whereby pathogenic molecules, microbes, or apoptotic cells (antigenic substances) are connected to antibodies, complement, or other proteins to attach to the cell surface receptors on phagocytes and NK cells). LMS (lipopolysaccharide)

Figure 2

The role of vitamin D regarding ACE in response to SARS-CoV-2. ACE: angiotensin-converting enzyme.