SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus.
SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus.
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DOI：
10.12688/wellcomeopenres.16002.2
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发表时间：
2020
影响因子：
--
通讯作者：
Zambon M
中科院分区：
文献类型：
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作者：
Andersson MI;Arancibia-Carcamo CV;Auckland K;Baillie JK;Barnes E;Beneke T;Bibi S;Brooks T;Carroll M;Crook D;Dingle K;Dold C;Downs LO;Dunn L;Eyre DW;Gilbert Jaramillo J;Harvala H;Hoosdally S;Ijaz S;James T;James W;Jeffery K;Justice A;Klenerman P;Knight JC;Knight M;Liu X;Lumley SF;Matthews PC;McNaughton AL;Mentzer AJ;Mongkolsapaya J;Oakley S;Oliveira MS;Peto T;Ploeg RJ;Ratcliff J;Robbins MJ;Roberts DJ;Rudkin J;Russell RA;Screaton G;Semple MG;Skelly D;Simmonds P;Stoesser N;Turtle L;Wareing S;Zambon M
背景：SARS-CoV-2感染（COVID-19的病因）的实验室诊断使用PCR检测呼吸道样本中的病毒RNA（vRNA）。SARS-CoV-2 RNA也在其他类型的样本中检测到，但对其在血液中检测的临床或实验室意义的了解有限。 研究方法：我们进行了系统的文献综述，以吸收血液中vRNA频率的证据，并确定相关的临床特征。我们对来自英国急性和恢复期COVID-19病例临床队列的血清样本（n=212）以及NHS血液和移植（NHSBT）收集的恢复期血浆样本（n=462额外样本）进行了RT-PCR。为了确定PCR阳性血液样本是否会造成感染风险，我们尝试从RNA阳性样本的子集中分离病毒。 结果：我们确定了28项相关研究，报告了0-76%血液样本中的SARS-CoV-2 RNA;合并估计值为10%（95%CI 5-18%）。在我们的临床队列的血清样本中，27/212（12.7%）通过RT-PCR检测到SARS-CoV-2 RNA。RNA检测发生在症状发作后20天的样本中，并且与更严重的疾病相关（多变量比值比7.5）。在症状发作后≥28天采集的所有样本中，0/494（0%，95%CI 0-0.7%）检出vRNA。在我们的PCR阳性样本中，循环阈值（ct）值较高（范围33.5-44.8），表明vRNA拷贝数较低。PCR阳性血清接种到细胞培养物中没有产生任何细胞病变效应或产生可检测的SARS-CoV-2 RNA的增加。RT-PCR阴性与总SARS-CoV-2抗体存在相关性（p=0.02）。 结论：在急性感染中收集的少数血清样本中，在低病毒载量下可检测到vRNA，但与传染性SARS-CoV-2无关（在所用检测方法的限制范围内）。这项工作有助于为处理来自当前或既往COVID-19患者的血液制品提供生物安全预防措施。
Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.