Original publication: Low serum 25‐hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID‐19 are associated with greater disease severity

Abstract

We thank Dr Brown for the insightful reading of our manuscript.1 We defined inpatients with severe COVID-19 as those requiring admission to the intensive therapy unit (ITU). It was rightly highlighted that this group did not include patients who were deemed inappropriate for escalation of care, so it is indeed possible that they had a higher prevalence of vitamin D deficiency (VDD), due to older age or multiple comorbidities, and therefore, a wider difference between ITU vs. non-ITU groups might have been shown; it may even have brought out a difference in mortality between the groups. However, this was beyond our primary aim to audit the local clinical care pathway with regards to diagnosing and treating VDD in patients with COVID-19. Although we acknowledge its major relevance to COVID-19 and VDD, we were unable to explore the effect of ethnicity, as our local patient demographic has an unusually low percentage of BAME population. Even though the Scientific Advisory Committee on Nutrition (SACN) has a minimalist definition of adequate vitamin D status (at least 25 nmol/L throughout the year, compared to the Endocrine Society recommended level of 75 nmol/L, for example), 48/134 (35.8%) of our patients had 25(OH)D levels below this threshold and, of those, 29 patients had 25(OH)D levels less than 15 nmol/L where there is a very real risk of osteomalacia. Only 13% of patients had levels above the 75 nmol/L threshold that other investigators suggest may be protective against COVID-19 (6). Furthermore, VDD prevalence may well have increased following prolonged lockdown measures and our data highlight a monumental failure of UK Public Health strategy, wherein the metabolic and immune health of the population has been compromised through longstanding and highly publicized sunlight avoidance advice of uncertain evidence benefit,2 without any counterbalancing vitamin D food fortification strategy. Indeed, ultraviolet B radiation (UVB) exposure that is necessary for vitamin D synthesis is estimated to reduce the number of deaths from COVID-19 in conjunction with social distancing measures.3 Furthermore, since the acceptance of our report, an erratum (and de facto partial retraction) of the UK Biobank prospective study now shows that historic lower 25(OH)D levels are associated with present higher risk for COVID-19,4, 5 which was also confirmed by a recent large Israeli study6 and by a more comprehensive and careful analysis of UK Biobank Data performed by other investigators.7 A recent commentary8 states that hospital-based clinical trials are underway elsewhere in the world, albeit National Institute for Health Research (NIHR) has declined to fund at least four UK grant applications for clinical trials of vitamin D3 in covid-19 disease prevention or mitigation. It may now be more challenging to definitively outline a signal for vitamin D supplementation in severe COVID-19 due to various factors, and results will certainly not be available for many months to come. In the interim, our data support the active diagnosis and prompt high-dose treatment of VDD as a safe and inexpensive strategy against COVID-19 infection, while more evidence is awaited. Moreover, there is need for an effective public health campaign to encourage greater population exposure to sunshine over this summer, along with active promotion of vitamin D supplementation as per SACN guidance before the onset of winter, rather than the present half-hearted efforts.

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