Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time.

Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time.
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DOI:
10.7554/elife.64683
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发表时间:
2021-07-12
期刊:
影响因子:
7.7
通讯作者:
COVID-19 Infection Survey team
COVID-19 Infection Survey team
中科院分区:
生物学1区
文献类型:
--
作者:
Walker AS;Pritchard E;House T;Robotham JV;Birrell PJ;Bell I;Bell JI;Newton JN;Farrar J;Diamond I;Studley R;Hay J;Vihta KD;Peto TE;Stoesser N;Matthews PC;Eyre DW;Pouwels KB;COVID-19 Infection Survey team

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在有代表性的社区监测中,关于SARS-CoV-2的信息有限,特别是周期阈值(Ct)值(病毒载量的替代指标)。我们收集了2020年4月26日至2021年3月13日英国全国新冠肺炎感染调查中所有阳性的鼻拭子和咽拭子,通过RT-PCRN、S和ORF1ab基因检测。我们用分位数回归研究了中位数CT值的预测因素。在3,312,159份鼻咽拭子中,27,902份(0.83%)为阳性,N、S和ORF1ab中的3、2或1个基因分别为10,317(37%)、11,012(40%)和6550(23%),中位数Ct=29.2(~215拷贝/ml;IQR Ct=21.9~32.8,14~56,400拷贝/ml)。低CTS(即更高的病毒载量)的独立预测因素包括自我报告的症状和检测到的更多基因,最多只有性别、种族和年龄的微小影响。单基因阳性患者几乎总是有Ct>30,但CTS在三基因阳性患者中差异很大,包括没有症状。人群水平的CTS随着时间的推移而变化,随着Ct的下降,SARS-CoV-2阳性率上升。首次逆转录聚合酶链式反应阳性的6189名受试者中,有4808名(78%)曾经抗体阳性,抗体阴性者的CTS显著高于阴性者。社区SARS-CoV-2 CT值的显著变化表明,它们可以作为一种有用的流行病学预警指标。英国医学研究理事会霍氏家族基金会,国立卫生研究院卫生与社会关爱部;惠康信托。
Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). We included all positive nose and throat swabs 26 April 2020 to 13 March 2021 from the UK’s national COVID-19 Infection Survey, tested by RT-PCR for the N, S, and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Of 3,312,159 nose and throat swabs, 27,902 (0.83%) were RT-PCR-positive, 10,317 (37%), 11,012 (40%), and 6550 (23%) for 3, 2, or 1 of the N, S, and ORF1ab genes, respectively, with median Ct = 29.2 (~215 copies/ml; IQR Ct = 21.9–32.8, 14–56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity, and age. Single-gene positives almost invariably had Ct > 30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4808 (78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody negative. Marked variation in community SARS-CoV-2 Ct values suggests that they could be a useful epidemiological early-warning indicator. Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.