Prevalence of CMV DNA in plasma from United States blood donors

BACKGROUND: Current interventions for CMV at-risk recipients include leukoreduction and CMV-antibody screening. We evaluated the CMV-DNA prevalence in United States (US) blood donors to estimate the residual risk from cell-free virus. METHODS: A highly sensitive, automated quantitative nucleic acid testing (NAT) assay assessed plasma samples in pools of 24 from CMV-seropositive or CMV-antibody not-tested donations. CMV-NAT-initial reactive (IR) samples were tested for CMV-IgG and IgM. CMV-NAT-reactive donors were invited to participate in follow-up (F/U) to confirm CMV seroconversion and DNA resolution. RESULTS: Of 240,115 CMV-DNA-tested samples, 23 were IR; titers ranged from 34.5 to 4020 IU/mL. Of 23 IR, 20 (87%) were CMV-NAT repeatedly reactive (RR); 3 (13%) were seroreactive only (repeat NAT-nonreactive/IgG-only positive). Of 20 CMV-NAT-RRs, 4 (20%) were CMV-IgG-only positive, 15 (75%) were IgM/IgG positive, and 1 (5%) was antibody-negative (i.e., window-period). F/U samples from 9 RR and 2 IR-only donors were collected at an 18-day mean after their IR donation. All F/U samples were NAT RR except those from the 2 IR-only donors, both NAT nonreactive. F/U IgG testing confirmed positivity in all 11 donors, with 8 of 11 also IgM positive. The mean age of CMV-NAT-reactive donors was 47 years; 16 (70%) were male, with 6 first-time donors. Previous donations (1999-2024) for 6 CMV-reactive donors were anti-CMV positive. A commercial infectivity assay yielded negative results for the 8 highest titer samples. CONCLUSIONS: Sensitive NAT determined a CMV-NAT-IR prevalence of 1:10,440 in plasma samples from CMV-screened seropositive/serology-unscreened US blood donors. One identified window-period donor highlights the limitation of current CMV interventions.