A Snapshot of the UK Blood Donor Plasma Virome: A Retrospective Cross‐Sectional Cohort Study

Estimates of population prevalence and genetic diversity of bloodborne viruses in healthy humans are essential to support population-scale monitoring for transfusion transmission risk. In the UK and globally, blood donations are routinely screened for a limited number of high-consequence pathogens, but the full composition of the plasma virome remains to be characterized. Using a novel quantitative targeted metagenomics sequencing approach, we analyzed previously unscreened plasma donations collected by NHS Blood and Transplant in England for all major pathogenic and known commensal human bloodborne viruses, and quantified their viral burden. Here we show that in a representative sample of 5064 UK blood donors in pools of 24 collected over a 1-month period, the virome was dominated by a small number of largely persistent species, representing < 10% (10/106) of previously identified human bloodborne viruses. The principal genera of human anelloviruses (TTV, TTMV and TTMDV) were detected in 89% of pools, albeit at low read count, inconsistent with measured anellovirus viral loads. In contrast, human pegivirus type 1 (HPgV-1), had an estimated population prevalence of 3.7% (95% CI 3.0%-4.4%), with high read count and complete genome recovery in around one half of positive pools, consistent with high titer in plasma. Less common detections included one species of gemykibovirus in five separate plasma pools, one hepatitis C virus (genotype 1a), and polyomaviruses and herpesviruses with prevalences between 0.04% (parvovirus 4, BK polyomavirus) to 0.41% (human herpesvirus 6). Phylogenetic analyses revealed mixed TTV, TTMV, and TTMDV populations and almost exclusively genotype 2 HPgV-1, consistent with known genotype distributions in Europe. Our results provide a baseline for describing the healthy plasma virome in UK blood donors.