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

Background. 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 postu-lated as a determinant of severity. Objectives. To review the evidence relevant to vitamin D and COVID-19. Methods. Narrative review. Results. 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 (P = 0.031) after adjust-ment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Fac-tors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, dia-betes and hypertension and these also associate with deficiency of vitamin D or its response. Vita-min D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vita-min D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angio-tensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. Conclusions. Substantial evidence supports a link between vitamin D deficiency and COVID-19 sever-ity 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 sup-plementation should be strongly advised for people likely to be deficient.