Longitudinal Detection of Twenty DNA and RNA Viruses in Allogeneic Hematopoietic Stem Cell Transplant Recipients Plasma

Abstract

Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients' plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT from 1 March 2017 to 31 January 2019 in this observational cohort study. Seventeen DNA and three RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays using plasma samples collected at 0, 1, 3, 6, and 12 months post HSCT. TTV infected 97% of patients, followed by HPgV-1 (prevalence: 26-36%). TTV (median 3.29 × 10⁵ copies/mL) and HPgV-1 (median 1.18 × 10⁶ copies/mL) viral loads peaked at month 3. At least one Polyomaviridae virus (BKPyV, JCPyV, MCPyV, HPyV6/7) was detected in >10% of patients. HPyV6 and HPyV7 prevalence reached 27% and 12% at month 3; CMV prevalence reached 27%. HSV, VZV, EBV, HHV-7, HAdV and B19V prevalence remained <5%. HPyV9, TSPyV, HBoV, EV and HPg-V2 were never detected. At month 3, 72% of patients had co-infections. TTV and HPgV-1 infections were highly prevalent. BKPyV, MCPyV and HPyV6/7 were frequently detected relative to classical culprits. Further investigation is needed into associations between these viral infections and immune reconstitution or clinical outcomes.

Keywords: PCR; TTV; anellovirus; blood; human pegivirus; polyomavirus; transplantation; virome; virus.

Figure 1

Priority order for virological testing on plasma samples. Patients in group 3 had screening for all 20 viral species (comprising viral species of groups 1, 2 and 3). Patients in group 2 were screened for 17 viral species (comprising viral species of group 1 and 2). Patients in group 1 were screened for 13 viral species only. Abbreviations: HSV-1/2: herpes simplex virus; VZV: varicella zoster virus; EBV: Epstein–Barr virus; CMV: cytomegalovirus: HHV-6A/B: human herpesvirus 6A/B; HHV-7: human herpes virus 7; JCPyV: JC polyomavirus; BKPyV: BK polyomavirus; MCPyV: Merkel cell polyomavirus; HPyV6: human polyomavirus 6; HPyV7: human polyomavirus 7; TSPyV: trichodysplasia spinulosa-associated polyomavirus; HPyV9: human polyomavirus 9; HAdV: human adenovirus; B19V: parvovirus B19; HBoV: human bocavirus; TTV: torque teno virus; EV: enterovirus; HPgV-1: human pegivirus 1; HPgV-2: human pegivirus 2.

Figure 2

Prevalence of plasma detection of the 9 viruses with a plasma detection prevalence above 10%. The graphs represent the prevalence of the 9 viruses with a prevalence of plasma detection above 10% at least at one time-point after transplantation. For each graph, green lines highlight the prevalence of plasma detection of one specific virus and grey lines represent the prevalence of plasma detection of the other 8 viruses. Abbreviations: TTV: torque teno virus; HPgV-1: human pegivirus 1; HPyV6: human polyomavirus 6; BKPyV: BK polyomavirus; JCPyV: JC polyomavirus; HPyV7: human polyomavirus 7; CMV: cytomegalovirus; MCPyV: Merkel cell polyomavirus; HHV-6: human herpesvirus 6.

Figure 3

Schematic representation of the plasma detection of viral species screened from D0 to Y1.

Figure 3

Schematic representation of the plasma detection of viral species screened from D0 to Y1.

Figure 4

Dot plots of TTV and HPgV-1 plasma viral load at each time-point. The graphs are represented in a logarithmic scale to improve readability. Grey lines represent median plasma viral loads.

Figure 5

Matrix of dual co-detections among patients of group 3 at M3. The matrix represents dual co-detections among the 63 patients of group 3 (20 viral species screened) with at least one virus detected at M3. Each number represents the number of patients for whom the two viruses were detected (other viral species possibly co-detected are not shown). Abbreviations: CMV: cytomegalovirus; HHV-6: human herpes virus 6; HHV-7: human herpes virus 7; JCPyV: JC polyomavirus; BKPyV: BK polyomavirus; MCPyV: Merkel cell polyomavirus; HPyV6: human polyomavirus 6; HPyV7: human polyomavirus 7; B19V: parvovirus B19; TTV: torque teno virus; HPgV-1: human pegivirus 1.