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

Rhodes, JM ORCID: 0000-0002-1302-260X, Subramanian, S ORCID: 0000-0002-6483-1730, Laird, E, Griffin, G and Kenny, RA (2020) Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis. Journal of Internal Medicine, 289 (1). pp. 97-115.

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Abstract

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 postulated 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 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. Conclusions 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.

Item Type:	Article
Uncontrolled Keywords:	vitamin D, COVID-19, cytokine
Depositing User:	Symplectic Admin
Date Deposited:	09 Sep 2020 10:36
Last Modified:	18 Jan 2023 23:34
DOI:	10.1111/joim.13149
Open Access URL:	http://doi.org/10.1111/joim.13149
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3100528