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

Abstract

Background: There is increasing evidence that vitamin D (VD) deficiency may increase individuals' risk of COVID-19 infection and susceptibility. We aimed to determine the relationship between VD deficiency and sufficiency and COVID-19 seropositivity within healthcare workers.

Methods: The study included an observational cohort of healthcare workers who isolated due to COVID-19 symptoms from 12 May to 22 May 2020, from the University Hospitals Birmingham National Health Service Foundation Trust. Data collected included SARS-CoV-2 seroconversion status, serum 25(OH)D₃ levels, age, body mass index (BMI), sex, ethnicity, job role and comorbidities. Participants were grouped into four VD categories: (1) Severe VD deficiency (VD<30 nmol/L); (2) VD deficiency (30 nmol/L ≤VD<50 nmol/L); (3) VD insufficiency (50 nmol/L ≤VD<75 nmol/L); (4) VD sufficiency (VD≥75 nmol/L).

Results: When VD levels were compared against COVID-19 seropositivity rate, a U-shaped curve was identified. This trend repeated when participants were split into subgroups of age, sex, ethnicity, BMI and comorbidity status. Significant difference was identified in the COVID-19 seropositivity rate between VD groups in the total population and between groups of men and women; black, Asian and minority ethnic (BAME) group; BMI<30 (kg/m²); 0 and +1 comorbidities; the majority of which were differences when the severely VD deficient category were compared with the other groups. A larger proportion of those within the BAME group (vs white ethnicity) were severely VD deficient (p<0.00001). A larger proportion of the 0 comorbidity subgroup were VD deficient in comparison to the 1+ comorbidity subgroup (p=0.046).

Conclusions: Our study has shown a U-shaped relationship for COVID-19 seropositivity in UK healthcare workers. Further investigation 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, allowing for targeted therapeutic treatment for those at risk.

Keywords: COVID-19; respiratory infection; viral infection.

Figure 1

SARS-CoV-2 seropositivity rate against serum VD levels by (A) Total, (B) Age group, (C) Ethnicity, (D) Sex, (E) BMI and (F) Presence of comorbidities. Seropositivity rate is defined as the number of SARS-CoV-2-positive cases, divided by the total number of cases. The data are represented by a weighted second-order polynomial regression smooth line. The line equation and the R² value are placed beside each corresponding line. BAME, black, Asian and minority ethnic; BMI, body mass index; VD, vitamin D.

Figure 2

Proportion of subgroup population by VD category. Each bar represents the proportion (%) of participants that is severely VD deficient (blue) and VD deficient (orange) within the total population (A) and when subgrouped according to age (B), ethnicity (C), sex (D), BMI (E) and comorbidity (F). Comparisons are made between the two subgroups to determine whether there is a significant difference in the proportion of the subgroup within each VD category. BAME, black, Asian and minority ethnic; BMI, body mass index, VD, vitamin D.

Figure 3

Relative proportions of paired subgroups within VD categories. The proportion (%) of participants who were 1=severely deficient, 2=deficient, 3=insufficient, 4=sufficient within the total population (A). For each of the subgroups of vitamin D status (categories 1–4), the proportion of those differing by age (B), ethnicity (C), sex (D), BMI (E) and comorbidity (F). BAME, black, Asian and minority ethnic; BMI, body mass index; VD, vitamin D.