Estimating infectiousness throughout SARS-CoV-2 infection course.
Estimating infectiousness throughout SARS-CoV-2 infection course.
复制标题
DOI：
10.1126/science.abi5273
复制
发表时间：
2021-07-09
期刊：
影响因子：
56.9
通讯作者：
Drosten, Christian
中科院分区：
文献类型：
--
作者：
Jones, Terry C.;Biele, Guido;Muhlemann, Barbara;Veith, Talitha;Schneider, Julia;Beheim-Schwarzbach, Joern;Bleicker, Tobias;Tesch, Julia;Schmidt, Marie Luisa;Sander, Leif Erik;Kurth, Florian;Menzel, Peter;Schwarzer, Rolf;Zuchowski, Marta;Hofmann, Joerg;Krumbholz, Andi;Stein, Angela;Edelmann, Anke;Corman, Victor Max;Drosten, Christian
无症状或轻度症状的严重急性呼吸综合征冠状病毒 2 型患者在病毒传播中的作用尚不清楚。琼斯等人。研究了患者的病毒载量，将那些几乎没有症状（如果有的话）的患者与住院病例进行比较。 2020 年 2 月至 2021 年 3 月，大约 40 万人（主要来自柏林）接受了检测，约 6% 的检测结果呈阳性。在 25,381 名阳性受试者中，约 8% 的病毒载量非常高。人们在感染后 2 天内就具有传染性，而在住院患者中，从病毒开始脱落到病毒载量达到峰值大约需要 4 天，该峰值发生在症状出现前 1 至 3 天。总体而言，病毒载量变化很大，但感染 B.1.1.7 变种的人的病毒载量大约高出 10 倍。儿童的病毒载量略低于成人，但这种差异可能没有临床意义。 《科学》，abi5273，本期第 14 页。 eabi5273 对德国数千名检测呈阳性的人的分析显示，许多人没有症状，少数人表现出高病毒载量。尽管事后研究揭示了严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 通过症状前、无症状和轻度症状 (PAMS) 病例传播的重要性，但其传染性的病毒学基础仍然很大程度上未量化。 B.1.1.7 等相关变异谱系迅速传播的原因尚未完全确定。患者样本中的病毒载量（病毒RNA浓度）以及从细胞培养的临床样本中分离病毒的成功率是与传染性以及传播最直接相关的临床参数。为了加深对 SARS-CoV-2 传染性的了解，特别是 PAMS 病例和 B.1.1.7 变体感染者，我们分析了 25,381 名德国病例的病毒载量数据，其中包括 9519 名住院患者、来自预约测试中心的 6110 名 PAMS 病例、1533 例 B.1.1.7 变体感染以及 4434 名（主要是住院患者）患者的病毒载量时间序列。然后将病毒载量结果与估计的细胞培养分离概率相结合，产生传染性的临床代理估计。 PAMS 受试者在第一次检测呈阳性时，其病毒载量和估计传染性仅略低于住院患者。同样，儿童的平均病毒载量仅略低于成人（0.5 log10 单位或更少），且约为成人峰值细胞培养物分离概率的 78%。 8% 的首次阳性病毒载量为每拭子 109 拷贝或更高，年龄范围广泛（平均 37.6 岁，标准差 13.4 岁），代表可能具有高度传染性的少数群体，其中三分之一是 PAMS。相对于非 B.1.1.7 病例，携带 B.1.1.7 变体的患者的病毒载量高出 10 倍，估计细胞培养物感染性高出 2.6 倍。 B.1.1.7 和 B.1.177 样本的病毒载量范围相似，能够在 Caco-2 细胞培养物中引起感染。时程分析估计，在脱落后 4.3 天达到每拭子 108.1 拷贝的峰值病毒载量，并表明，在整个感染过程中，住院患者的病毒载量略高于非住院病例，而非住院病例的病毒载量又略高于 PAMS 病例。在 PAMS 受试者的首次阳性检测中观察到较高的病毒载量，这可能是系统性早期检测的结果。平均培养物分离概率在病毒载量峰值后 5 天下降至 0.5，在病毒载量峰值后 10 天下降至 0.3。我们估计病毒载量每天下降 0.17 log10 单位，结合报告的孵化时间和细胞培养物分离成功时间的估计值，表明病毒载量在症状出现前 1 至 3 天达到峰值（在有症状的病例中）。在未预约检测中心检测呈阳性的 PAMS 受试者预计其传染性与住院患者大致相同。 PAMS 人群的预期传染性病毒排出水平非常重要，因为在检测到感染时，他们正在社区中传播。尽管病毒载量和细胞培养感染性不能直接转化为传播概率，但 B.1.1.7 变种的快速传播可能部分归因于这些病例中较高的病毒载量。例如，可以使用易于测量的病毒学参数来估计不同群体（按年龄、性别、临床状态等）的传播风险，量化方差，显示病毒变体的差异，突出和量化过度扩散，并为检疫、遏制和消除策略提供信息。 (A) 症状前、无症状和轻度症状病例（PAMS；红色）、住院患者（蓝色）和其他受试者（黑色）的病毒载量。 (B) 预期首次阳性病毒载量和细胞培养物分离概率，颜色如 (A) 所示。 (C) 用代表患者的线进行时间估计，颜色如 (A) 所示。 (D) 与 (C) 相同，但按年龄着色。量化病毒感染和脱落的两个基本参数是病毒载量以及样品是否在细胞培养物中产生复制的病毒分离株。我们检查了德国 25,381 例严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 病例，其中 6110 例来自测试中心，有症状前、无症状和轻度症状 (PAMS) 受试者，9519 例住院患者，以及 1533 例 B.1.1.7 谱系感染。最年轻受试者的病毒载量比年长受试者低 0.5（或更少）log10 单位，并且他们显示出约 78% 的峰值细胞培养复制概率；部分原因是拭子尺寸较小，不太可能与临床相关。 8% 的受试者中每个拭子的病毒载量超过 109 拷贝，其中三分之一是 PAMS，平均年龄为 37.6 岁。我们估计从开始脱落到病毒载量峰值（每个拭子 108.1 个 RNA 拷贝）和细胞培养物分离概率峰值（0.75）需要 4.3 天。 B.1.1.7受试者的平均log10病毒载量比非B.1.1.7受试者高1.05，并且B.1.1.7受试者的估计细胞培养物复制概率高出2.6倍。
The role that individuals with asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 have in transmission of the virus is not well understood. Jones et al. investigated viral load in patients, comparing those showing few, if any, symptoms with hospitalized cases. Approximately 400,000 individuals, mostly from Berlin, were tested from February 2020 to March 2021 and about 6% tested positive. Of the 25,381 positive subjects, about 8% showed very high viral loads. People became infectious within 2 days of infection, and in hospitalized individuals, about 4 days elapsed from the start of virus shedding to the time of peak viral load, which occurred 1 to 3 days before the onset of symptoms. Overall, viral load was highly variable, but was about 10-fold higher in persons infected with the B.1.1.7 variant. Children had slightly lower viral loads than adults, although this difference may not be clinically significant. Science, abi5273, this issue p. eabi5273 Analysis of thousands of people who tested positive in Germany reveals that many were asymptomatic and a minority exhibited high viral loads. Although post facto studies have revealed the importance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from presymptomatic, asymptomatic, and mildly symptomatic (PAMS) cases, the virological basis of their infectiousness remains largely unquantified. The reasons for the rapid spread of variant lineages of concern, such as B.1.1.7, have yet to be fully determined. Viral load (viral RNA concentration) in patient samples and the rate of isolation success of virus from clinical specimens in cell culture are the clinical parameters most directly relevant to infectiousness and hence to transmission. To increase our understanding of the infectiousness of SARS-CoV-2, especially in PAMS cases and those infected with the B.1.1.7 variant, we analyzed viral load data from 25,381 German cases, including 9519 hospitalized patients, 6110 PAMS cases from walk-in test centers, 1533 B.1.1.7 variant infections, and the viral load time series of 4434 (mainly hospitalized) patients. Viral load results were then combined with estimated cell culture isolation probabilities, producing a clinical proxy estimate of infectiousness. PAMS subjects had, at the first positive test, viral loads and estimated infectiousness only slightly less than hospitalized patients. Similarly, children were found to have mean viral loads only slightly lower (0.5 log10 units or less) than those of adults and ~78% of the adult peak cell culture isolation probability. Eight percent of first-positive viral loads were 109 copies per swab or higher, across a wide age range (mean 37.6 years, standard deviation 13.4 years), representing a likely highly infectious minority, one-third of whom were PAMS. Relative to non-B.1.1.7 cases, patients with the B.1.1.7 variant had viral loads that were higher by a factor of 10 and estimated cell culture infectivity that was higher by a factor of 2.6. Similar ranges of viral loads from B.1.1.7 and B.1.177 samples were shown to be capable of causing infection in Caco-2 cell culture. A time-course analysis estimates that a peak viral load of 108.1 copies per swab is reached 4.3 days after onset of shedding and shows that, across the course of infection, hospitalized patients have slightly higher viral loads than nonhospitalized cases, who in turn have viral loads slightly higher than PAMS cases. Higher viral loads are observed in first-positive tests of PAMS subjects, likely as a result of systematic earlier testing. Mean culture isolation probability declines to 0.5 at 5 days after peak viral load and to 0.3 at 10 days after peak viral load. We estimate a rate of viral load decline of 0.17 log10 units per day, which, combined with reported estimates of incubation time and time to loss of successful cell culture isolation, suggests that viral load peaks 1 to 3 days before onset of symptoms (in symptomatic cases). PAMS subjects who test positive at walk-in test centers can be expected to be approximately as infectious as hospitalized patients. The level of expected infectious viral shedding of PAMS people is of high importance because they are circulating in the community at the time of detection of infection. Although viral load and cell culture infectivity cannot be translated directly to transmission probability, it is likely that the rapid spread of the B.1.1.7 variant is partly attributable to higher viral load in these cases. Easily measured virological parameters can be used, for example, to estimate transmission risk from different groups (by age, gender, clinical status, etc.), to quantify variance, to show differences in virus variants, to highlight and quantify overdispersion, and to inform quarantine, containment, and elimination strategies. (A) Viral loads in presymptomatic, asymptomatic, and mildly symptomatic cases (PAMS; red), hospitalized patients (blue), and other subjects (black). (B) Expected first-positive viral load and cell culture isolation probability, colored as in (A). (C) Temporal estimation with lines representing patients, colored as in (A). (D) As in (C), but colored by age. Two elementary parameters for quantifying viral infection and shedding are viral load and whether samples yield a replicating virus isolate in cell culture. We examined 25,381 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Germany, including 6110 from test centers attended by presymptomatic, asymptomatic, and mildly symptomatic (PAMS) subjects, 9519 who were hospitalized, and 1533 B.1.1.7 lineage infections. The viral load of the youngest subjects was lower than that of the older subjects by 0.5 (or fewer) log10 units, and they displayed an estimated ~78% of the peak cell culture replication probability; in part this was due to smaller swab sizes and unlikely to be clinically relevant. Viral loads above 109 copies per swab were found in 8% of subjects, one-third of whom were PAMS, with a mean age of 37.6 years. We estimate 4.3 days from onset of shedding to peak viral load (108.1 RNA copies per swab) and peak cell culture isolation probability (0.75). B.1.1.7 subjects had mean log10 viral load 1.05 higher than that of non-B.1.1.7 subjects, and the estimated cell culture replication probability of B.1.1.7 subjects was higher by a factor of 2.6.
登录
查看更多内容
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
影响因子：
82.9
作者：
Adam, Dillon C.;Wu, Peng;Cowling, Benjamin J.
通讯作者：
Cowling, Benjamin J.
影响因子：
11.8
作者：
Bullard, Jared;Dust, Kerry;Poliquin, Guillaume
通讯作者：
Poliquin, Guillaume
影响因子：
9.2
作者：
Danecek P;Bonfield JK;Liddle J;Marshall J;Ohan V;Pollard MO;Whitwham A;Keane T;McCarthy SA;Davies RM;Li H
通讯作者：
Li H
DOI：
10.1136/bmj.n579
发表时间：
2021-03-09
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Challen R;Brooks-Pollock E;Read JM;Dyson L;Tsaneva-Atanasova K;Danon L
通讯作者：
Danon L