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Persistent viral RNA shedding in COVID-19: Caution, not fear

机译:在Covid-19中持续的病毒RNA脱落:谨慎,不是恐惧

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With the continued community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, the efficacy of laboratory testing in mitigating and supressing viral spread has received increasing interest and concern. SARS-CoV-2 can be transmitted by a carrier who is unaware of the infection, and a body of evidence has demonstrated that viral transmission from asymptomatic and pre-symptomatic subjects has underpinned the current pandemic [1]. Nucleic acid amplification tests (NAATs), particularly real time reverse transcription polymerase chain reaction (rRT-PCR) assays, used since the beginning of the pandemic in order to accurately detect the virus, are considered the operational gold standard for diagnosing and confirming Coronavirus 2019 disease (COVID-19) [2]. However, in addition to the false negative rates ranging from 2 to 29% as reported in studies finding that negative rRTPCR tests were positive at repeat testing [3], the continuing PCR positivity compared with the risk of transmission remains a major concern. Persistently or intermittently PCR positive individuals raise the question of the true risk of disease transmission, and the safe duration of self-isolation. This in turn, is a major problem not only for individual patients and relatives, but also for the population at large in the preventing community transmission and enabling a safe return to the workplace and the resumption of social activities. The new insights gained in the paper by Line K Vibholm and colleagues, published recently in EbioMedicine allow a greater understanding of the prolonged RNA detection in pharyngeal swabs from COVID-19 patients, the risk associated with this finding, and the immunological responses in convalescent individuals with a history of rRT-PCR verified SARS-CoV-2 infection [4]. Two hundred and three patients with documented SARS-CoV-2 PCR positivity 12 weeks prior to the study who had fully recovered from COVID-19 were monitored at two time points (time point 1: 14 days-12 weeks after positive PCR; time point 2: 6-10 weeks after time point 1) using digital PCR (ddPCR) to detect viral RNA on pharyngeal swabs. ddPCR assures maximal sensitivity (100%) in detecting SARS-CoV-2, allowing for the absolute quantitation of copy numbers [5]. Twenty-six individuals (12.8%) were positive for SARS-CoV-2 at time 1 while, at time point 2, five (5.3%) were found to be positive (up to 105 days after recovery), and a subset of participants had remarkably high viral loads (103 copies per swab). This value is comparable to that found in acutely affected COVID-19 patients, even if sampling was performed more than four weeks after symptom onset. Therefore, overall in enrolled participants, SARSCoV-2 PCR positivity declined over time, but viral RNA was detected in some individuals up to 109 days after symptom onset, and COVID19 patients with mild or asymptomatic disease (group 1) were more likely to be persistently PCR positive than participants with a more severe illness (groups 2 and 3). Two hundred and two participants (99.5%) seroconverted at time point 1, at a median of 45 days after symptom onset, and no difference was found between the PCR-positive and PCR-negative groups for specific antibodies level. However, higher total antibodies levels were found to be associated with a lower likelihood of persistent viral RNA shedding (fewer SARS-CoV-2 copies per swab). Unfortunately, the authors did not measure neutralizing antibodies even if the serological assays used have been reported to assure results well related to neutralization activity [6]. Participants with a higher pharyngeal viral load presented an increased breadth and magnitude of SARS-specific CD8 T-cell responses, the CD8 T-cell response magnitude being significantly correlated with SARS-CoV-2 copies per swab.
机译:随着全球严重急性呼吸综合征冠状病毒2(SARS-COV-2)的持续群落传播,实验室检测在缓解和抑制病毒传播中的疗效得到了越来越关注的兴趣和关注。 SARS-COV-2可以由不知道感染的载体传播,并且证据证明了来自无症状和前症状受试者的病毒传播造成了目前的大流行[1]。核酸扩增试验(Naats),特别是实时逆转录聚合酶链反应(RRT-PCR)测定,以便自大流行开始以便准确地检测病毒,被认为是诊断和确认冠状病毒2019的运营金标准疾病(Covid-19)[2]。然而,除了在研究中报告的2%至29%的假阴性率,发现负rRTPCR试验在重复测试中阳性[3],与传播风险相比,继续PCR阳性仍然是一个主要问题。持续或间歇性PCR阳性个体提出了疾病传播风险的问题,以及自隔离的安全持续时间。这反过来,这是一个不仅适用于个体患者和亲属的主要问题,也是在防止社区传播中的群体中的人口,并能够安全回归工作场所和恢复社会活动。 eBiomedicine最近发表于eBiomedicine的Kvibholm及其同事中所获得的新见解,允许更加了解来自Covid-19患者的咽部拭子的延长RNA检测,与这种发现相关的风险以及康复人员中的免疫反应具有RRT-PCR的历史验证SARS-COV-2感染[4]。在两次从Covid-19完全回收的研究之前,两三次有记录的SARS-COV-2 PCR积极性12周监测(时间点1:14天 - 12周后阳性PCR;时间点2:: 6-10周后的时间点1)使用数字PCR(DDPCR)检测咽部拭子上的病毒RNA。 DDPCR确保在检测SARS-COV-2中的最大灵敏度(100%),允许拷贝数的绝对定量[5]。在时间1的时间为SARS-COV-2阳性的二十六个个体(12.8%)呈阳性1,而在时间点2,5(5.3%)被发现是阳性的(恢复后最多105天),以及参与者的子集具有显着的病毒载荷(每拭子103份)。即使在症状发作后超过四周进行抽样,这种价值也与急性受Covid-19患者中发现的相当。因此,总的来说,在注册的参与者中,SARSCOV-2 PCR阳性随着时间的推移而下降,但在症状发作后的一些个体中检测到病毒RNA,并且患有轻度或无症状疾病(第1组)的Covid19患者更容易持续存在PCR阳性比参与者更严重的疾病(第2组和第3组)。在症状发作症状发作后45天的中位数,两百和25%的参与者(99.5%)在时间点1,在45天后,PCR阳性和PCR阴性群体的特异性抗体水平没有差异。然而,发现较高的总抗体水平与持续的病毒RNA脱落的较低可能性相关(每拭子的较少的SARS-COV-2拷贝)相关。不幸的是,作者即使据报道使用使用的血清学检测以确保与中和活性有关的结果[6],也没有测量中和抗体。具有更高咽部病毒载体的参与者提高了SARS特异性CD8 T细胞反应的增加和大小,CD8 T细胞响应幅度与每个拭子的SARS-COV-2拷贝显着相关。

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    《EBioMedicine》 |2021年第a期|共2页
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    Mario Plebani;

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