SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021.
SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021.
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2021 年夏季之前，与特拉华谷疫苗突破相关的 SARS-CoV-2 变体。
DOI：
10.1101/2021.10.18.21264623
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Bianco,Colleen
中科院分区：
文献类型：
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作者：
Marques,AndrewD;Sherrill-Mix,Scott;Everett,John;Reddy,Shantan;Hokama,Pascha;Roche,AoifeM;Hwang,Young;Glascock,Abigail;Whiteside,SamanthaA;Graham-Wooten,Jevon;Khatib,LaylaA;Fitzgerald,AyannahS;Moustafa,AhmedM;Bianco,Colleen
严重急性呼吸道冠状病毒-2 (SARS-CoV-2) 是导致全球爆发 COVID-19 的原因。有证据表明，该病毒正在进化，可以在人群中有效传播，包括接种疫苗的个体。在这里，我们报告了一项对特拉华谷（包括费城市）监测中的病毒变体以及感染疫苗接种对象的病毒变体的研究。我们对 2020 年 3 月至 2021 年 9 月期间 2621 个监测样本的完整病毒基因组进行了测序和分析，并将其与 159 个疫苗突破的基因组序列进行了比较。 2020 年初春，所有检测到的变体均为 B.1 及其密切相关的谱系。接下来是谱系的混合，特别是包括 B.1.243，然后是 B.1.1.7（α），其他谱系以较低水平存在。后来的分离以 B.1.617.2 (delta) 和其他 delta 谱系为主； delta 是上次采样时出现的唯一变体。为了调查疫苗突破中是否优先出现任何变异，我们设计了一个基于贝叶斯自回归移动平均逻辑多项式回归的模型，以进行严格比较。这表明 B.1.617.2 (delta) 在疫苗突破病例中表现出 3 倍富集（比值比为 3；95% 可信区间为 0.89-11）。病毒点替换也可能与疫苗突破相关，特别是在 α、β 和 γ 变体中发现的 N501Y 替换（比值比 2.04；95% 可信区间为 1.25-3.18）。因此，本研究概述了特拉华谷的病毒进化和疫苗突破，并引入了严格的统计方法来研究不断变化的背景下突破性变体的富集情况。 重要性 SARS-CoV-2 疫苗接种对于减少病毒感染、住院和死亡非常有效。然而，疫苗突破性感染已被广泛观察到，这引发了特定病毒变体或病毒突变是否与突破性感染相关的问题。在此，我们报告了对宾夕法尼亚州东南部特拉华谷诊断出的 2621 例新冠肺炎 (COVID-19) 患者的监测分离株进行的分析，以便与 159 例疫苗突破病例标本进行严格比较。我们的最佳估计是突破中某些 delta 谱系富集了 3 倍，并且显着的尖峰替代 N501Y 富集。我们引入的统计方法应该广泛用于评估疫苗突破和其他病毒表型。
The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25–3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background.IMPORTANCESARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.