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 characterised. Using a novel quantitative targeted metagenomics sequencing approach, we analysed 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 5,064 UK blood donors in pools of 24 collected over a one-month period, the virome was dominated by a small number of largely persistent species, representing ~11% (12/106) of previously identified human bloodborne viruses. Anelloviruses (TTV, TTMV and TTMDV) was detected in 89.0% of pools, albeit at low read count inconsistent with measured anellovirus viral loads. In contrast, human pegivirus type 1 (HPgV-1), had 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 titre in plasma. Estimated prevalences for less common detections included one species of gemykibovirus (0.12%), hepatitis C virus (genotype 1a, 0.04%) and various polyomaviruses and herpesviruses between 0.04% (parvovirus 4, BK polyomavirus) and 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.