Highly Sensitive Quantification of Plasma Severe Acute Respiratory Syndrome Coronavirus 2 RNA Sheds Light on its Potential Clinical Value
Highly Sensitive Quantification of Plasma Severe Acute Respiratory Syndrome Coronavirus 2 RNA Sheds Light on its Potential Clinical Value
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DOI：
10.1093/cid/ciaa1196
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发表时间：
2021-11-01
影响因子：
11.8
通讯作者：
Pere, Helene
中科院分区：
文献类型：
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作者：
Veyer, David;Kerneis, Solen;Pere, Helene
背景2019冠状病毒病（COVID-19）是一个全球性的公共卫生问题，已导致全球超过662 000人死亡。虽然COVID-19的临床表现以呼吸道症状为主，但一些患者会出现其他严重损害，如心血管、肾脏和肝脏损伤，和/或多器官衰竭，这表明严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在血液中传播。最近的超灵敏聚合酶链反应（PCR）技术现在允许绝对定量血浆中的核酸。我们打算使用基于液滴的数字PCR技术来获得对住院COVID-19患者的血浆SARS-CoV-2病毒载量（SARS-CoV-2 RNAemia）的灵敏检测和精确定量。分析了58名连续的COVID-19肺炎患者在症状发作后8至12天和12名健康对照。17例患者的疾病严重程度被分类为轻度至中度，16例为重度，26例为危重。血浆SARS-CoV-2 RNA血症通过液滴数字晶体数字PCR下一代技术（Stilla Technologies，Villejuif，France）定量。总体而言，在43例（74.1%）患者中检测到SARS-CoV-2 RNA血症。SARS-CoV-2 RNA血症阳性的患病率与疾病严重程度相关，范围从轻中度患者的53%到重症患者的88%（P = 0.036）。SARS-CoV-2 RNA血症水平与严重程度相关（P = 0.035）。在随访期间发生临床恶化的9例患者中，8例基线时SARS-CoV-2 RNA血症阳性，而仅1例在分析时未检测到SARS-CoV-2 RNA血症的危重患者在第27天死亡。通过基于液滴的数字PCR测量的SARS-CoV-2 RNAemia构成了COVID-19患者中有希望的预后生物标志物。
Background. Coronavirus disease 2019 (COVID-19) is a global public health problem that has already caused more than 662 000 deaths worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, some patients present other severe damage such as cardiovascular, renal and liver injury, and/or multiple organ failure, suggesting a spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in blood. Recent ultrasensitive polymerase chain reaction (PCR) technology now allows absolute quantification of nucleic acids in plasma. We intend to use the droplet-based digital PCR technology to obtain sensitive detection and precise quantification of plasma SARS-CoV-2 viral load (SARS-CoV-2 RNAemia) in hospitalized COVID-19 patients.Methods. Fifty-eight consecutive COVID-19 patients with pneumonia 8 to 12 days after onset of symptoms and 12 healthy controls were analyzed. Disease severity was categorized as mild to moderate in 17 patients, severe in 16, and critical in 26. Plasma SARS-CoV-2 RNAemia was quantified by droplet digital Crystal Digital PCR next-generation technology (Stilla Technologies, Villejuif, France).Results. Overall, SARS-CoV-2 RNAemia was detected in 43 (74.1%) patients. Prevalence of positive SARS-CoV-2 RNAemia correlated with disease severity, ranging from 53% in mild-to-moderate patients to 88% in critically ill patients (P =.036). Levels of SARS-CoV-2 RNAemia were associated with severity (P =.035). Among 9 patients who experienced clinical deterioration during follow-up, 8 had positive SARS-CoV-2 RNAemia at baseline, whereas only 1 critical patient with undetectable SARS-CoV-2 RNAemia at the time of analysis died at day 27.Conclusion. SARS-CoV-2 RNAemia measured by droplet-based digital PCR constitutes a promising prognosis biomarker in COVID-19 patients.