de Campos Gabriel Montenegro, de Mello Costa Thalita Cristina, Silveira Roberta Maraninchi, Valença Ian Nunes, Bezerra Rafael Dos Santos, Darrigo Junior Luiz Guilherme, Vieira Ana Carolina de Jesus, Mesquita Camila Campos, Laurindo Patrícia da Silva, Cunha Renato Guerino, Kashima Simone, Covas Dimas Tadeu, Simões Belinda Pinto, Sampaio Sandra Coccuzzo, Elias Maria Carolina, Giovanetti Marta, Slavov Svetoslav Nanev
Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 05508-220, SP, Brazil.
Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14040-900, SP, Brazil.
Microorganisms. 2024 Dec 12;12(12):2557. doi: 10.3390/microorganisms12122557.
Viral infections are one of the most important causes of morbidity and mortality among patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Immunosuppression may lead to the reactivation of latent viruses or the acquisition of new infections, resulting in severe clinical outcomes. The early detection of viral reactivations is crucial for effective patient management and post-transplant care. In this study, we employed next-generation metagenomics to assess changes in viral abundance and detect clinically significant viruses in allogeneic HSCT patients. A total of 20 patients from the Transplant Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo were included, with plasma samples collected at three time points: D + 0 (pre-transplantation), D + 30 (30 days post-transplantation), and D + 100 (~100 days post-transplantation). A higher presence of clinically relevant viruses, such as the cytomegalovirus (CMV), the Epstein-Barr virus (EBV) and adenoviruses, were predominantly detected at D + 30. The diversity of commensal viruses, primarily anelloviruses, increased gradually, with the highest abundance and variability detected at D + 100. Viruses with clinical importance for HSCT, including CMV, adenovirus and EBV, were confirmed and characterized at the molecular level, showing generally high cycle threshold values. Our findings demonstrate a rise in anellovirus abundance following allogeneic HSCT, with the highest levels observed at D + 100. Notably, D + 30 was identified as a critical time point for the reactivation of clinically significant viruses. This study underscores the potential of metagenomics in the identification of clinically relevant viruses and highlights the importance of monitoring latent viruses in immunocompromised populations, including allogeneic HSCT patients.
病毒感染是接受异基因造血干细胞移植（HSCT）患者发病和死亡的最重要原因之一。免疫抑制可能导致潜伏病毒重新激活或感染新病毒，从而产生严重的临床后果。病毒重新激活的早期检测对于有效的患者管理和移植后护理至关重要。在本研究中，我们采用下一代宏基因组学来评估异基因HSCT患者病毒丰度的变化并检测具有临床意义的病毒。圣保罗大学医学院里贝朗普雷图分校大学医院移植科共纳入20例患者，在三个时间点采集血浆样本：D + 0（移植前）、D + 30（移植后30天）和D + 100（移植后约100天）。在D + 30时主要检测到更多具有临床相关性的病毒，如巨细胞病毒（CMV）、爱泼斯坦-巴尔病毒（EBV）和腺病毒。共生病毒（主要是指环病毒）的多样性逐渐增加，在D + 100时检测到最高丰度和变异性。对HSCT具有临床重要性的病毒，包括CMV、腺病毒和EBV，在分子水平上得到确认和表征，显示出普遍较高的循环阈值。我们的研究结果表明异基因HSCT后指环病毒丰度升高，在D + 100时观察到最高水平。值得注意的是，D + 30被确定为具有临床意义的病毒重新激活的关键时间点。本研究强调了宏基因组学在识别临床相关病毒方面的潜力，并突出了监测免疫功能低下人群（包括异基因HSCT患者）中潜伏病毒的重要性。
