Vitamin D Status: A U-shaped relationship for SARS-CoV-2 seropositivity in UK healthcare workers

Mackay, W. R.; Lugg, S. T.; Faniyi, A. A.; Faustini, S.; Webster, C.; Duffy, J.; Hewison, M.; Shields, A.; Richter, A. A.; Parekh, D.; Scott, A.; Thickett, D. R.

Background: Vitamin D has numerous mechanistic roles within the immune system. There is increasing evidence to suggest Vitamin D deficiency may increase individuals risk of COVID-19 infection and susceptibility. We aimed to determine the relationship between severity of vitamin D deficiency and sufficiency and COVID-19 infection within healthcare workers. Methods: The study included an observational cohort of healthcare workers who isolated due to COVID-19 symptoms from 12th to 22nd May 2020, from the University Hospitals Birmingham NHS Foundation Trust (UHBFT). This was part of the COVID-19 convalescent immunity study (COCO). Data collected included SARS-CoV-2 seroconversion status, serum 25(OH)D3 levels as well as age, body mass index (BMI), sex, ethnicity, job role, and co-morbidities. Participants were grouped into four vitamin D (VD) categories. 1) Severe VD deficiency (VD <30 nmol/L); 2) VD deficiency (VD > or equal to 30 nmol/L and <50 nmol/L); 3) VD insufficiency (VD > or equal to 50 nmol/L and <75 nmol/L); 4) VD sufficiency (VD > or equal to 75 nmol/L). Results: When VD levels were compared against COVID-19 seropositivity rate, a U-shaped curve was identified in the total population. This trend repeated when split into subgroups of age, sex, ethnicity, BMI, and co-morbidity status. Significant difference was identified in the COVID-19 seropositivity rate between VD groups between multiple VD groups in the total population, males, females, BAME, BMI<30 (kg/m2), 0 and +1 comorbidities; the majority of which were differences when the severely VD deficient category were compared to the other group. A significantly larger proportion of those within the Black, Asian, minority ethnic (BAME) group (vs. white ethnicity) were severely vitamin D deficient (P <0.00001). A significantly higher proportion of the 0-comorbidity subgroup were vitamin D deficient in comparison to the 1+ comorbidity subgroup (P = 0.046). Conclusions: Further investigation of the U-shaped curves is required to determine whether high VD levels can have a detrimental effect on susceptibility to COVID-19 infection. Future randomised clinical trials of VD supplementation could potentially identify optimal VD levels. This would allow for targeted therapeutic treatment for those at-risk such as in the BAME group.