Jefferson T, Spencer E A, Conly J M, Rosca E C, Maltoni S, Brassey J, Onakpoya I J, Evans D H, Heneghan C J, Plüddemann A
Department for Continuing Education, University of Oxford, Oxford, UK.
Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
J Hosp Infect. 2023 Feb;132:62-72. doi: 10.1016/j.jhin.2022.11.018. Epub 2022 Dec 5.
Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation.
To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients.
LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1 November 2019 to 26 October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically.
Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms.
Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.
由于免疫抑制，实体器官和造血干细胞移植受者比非移植受者更容易感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2），并且可能构成持续的传播风险，尤其是在医院环境中。详细的病例报告，包括症状、病毒载量和传染性（通过培养中存在具有复制能力的病毒来定义），为研究临床病程、负担和传染性之间的关系提供了机会，并为解除隔离提供指导。
研究SARS-CoV-2逆转录聚合酶链反应（RT-PCR）连续循环阈值（Ct）值或定量循环值，或其他病毒载量指标与基于病毒培养的传染性病毒存在的可能性和持续时间之间的关系，包括年龄、性别、基础疾病、免疫抑制程度和/或疫苗接种对移植受者这种关系的影响。
检索了2019年11月1日至2022年10月26日的LitCovid、medRxiv、谷歌学术和世界卫生组织COVID-19数据库。本系统评价纳入了报告SARS-CoV-2感染移植受者相关数据（连续RT-PCR检测结果和同一呼吸道样本的病毒培养数据）的研究：使用五项标准评估方法学质量，并对数据进行叙述性和图形化综合分析。
本评价纳入了13份病例报告和病例系列，涉及41名移植受者（22名肾移植、5名心脏移植、1名骨髓移植、2名肝移植、1名双侧肺移植和10名血液干细胞移植）。观察到病毒载量指标与具有复制能力的SARS-CoV-2脱落可能性之间存在关联。三名个体在症状出现后100多天内排出具有复制能力的病毒。检测和报告平台缺乏标准化，无法确定明确的病毒载量临界值。然而，尽管各平台存在差异，但大多数移植受者在Ct值>30时停止排出具有复制能力的病毒。
在考虑每位患者的临床状况时，病毒载量是传染性的合理指标。标准化的研究设计和报告对于基于不断增加的证据库来规范指导至关重要。
