Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>SARS‐CoV‐2 coronavirus infection ranges from asymptomatic through to fatal COVID‐19 characterized by a ‘cytokine storm’ and lung failure. Vitamin D deficiency has been postulated as a determinant of severity.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To review the evidence relevant to vitamin D and COVID‐19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Narrative review.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID‐19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (<jats:italic>P</jats:italic> = 0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID‐19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin‐converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Substantial evidence supports a link between vitamin D deficiency and COVID‐19 severity but it is all indirect. Community‐based placebo‐controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID‐19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile, vitamin D supplementation should be strongly advised for people likely to be deficient.</jats:p></jats:sec>