Unmasking viral sequences by metagenomic next-generation sequencing in adult human blood samples during steroid-refractory/dependent graft-versus-host disease

Background: Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort of patients at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated viral pipeline and de novo analysis on pooled stored routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal and unexpected viruses. Results: Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nuc...背景：病毒感染是异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation, allo-HSCT）后常见的并发症。合并激素难治/依赖性移植物抗宿主病（graft-versus-host disease, GvHD）的allo-HSCT受者存在重度免疫抑制，感染弱致病性或共生病毒的风险显著升高。本研究于2016至2019年间，在日内瓦大学医院纳入25例成人allo-HSCT受者，均患有急性或慢性激素难治/依赖性GvHD，将其纳入患者前瞻性队列。研究采用经过验证的病毒分析流程，对采集于强化类固醇治疗或二线GvHD治疗周期内的混合储存常规临床血浆样本，开展宏基因组下一代测序（metagenomics next-generation sequencing, mNGS）及从头分析，以识别弱致病性、共生及意外病毒。 结果：强化免疫抑制的中位持续时间为5.1个月（四分位间距IQR 5.5）。GvHD相关死亡率为36%。mNGS检测到病毒核酸……