ABSTRACT
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)D 3 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 (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 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/m 2 ), 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.
Subject(s)
COVID-19 , Vitamin D DeficiencyABSTRACT
Rational: Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify tractable therapeutic targets. Objectives: Examine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC) Methods: Isolated neutrophils from 41 hospitalised, non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured. Results: Compared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO (p<0.0001), VEGF (p<0.0001), TNFRI (p<0.0001) and IL-6 (p=0.009) were elevated in COVID-19, which positively correlated with disease severity by 4C score. Conclusion: COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.