From the Big Data Institute (D.W.E.) and the Health Economics Research Centre (K.B.P.), the Nuffield Department of Population Health, National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (D.W.E., K.B.P., A.S.W., T.E.A.P.), and the Nuffield Department of Medicine (A.S.W., T.E.A.P.), University of Oxford, Oxford, and the Department of Health and Social Care, National Health Service Test and Trace (D.T., M.P., T.F.), Deloitte MCS (D.C.), and William Harvey Research Institute, Queen Mary University of London (T.F.), London - all in the United Kingdom.
N Engl J Med. 2022 Feb 24;386(8):744-756. doi: 10.1056/NEJMoa2116597. Epub 2022 Jan 5.
Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission.
We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2-infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination.
Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 nCoV-19 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination.
Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission. (Funded by the U.K. Government Department of Health and Social Care and others.).
在严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)的 B.1.617.2(德尔塔)变体出现之前,疫苗接种通过降低感染者的病毒载量,从而降低了感染者传播 SARS-CoV-2 的可能性。尽管疫苗接种仍能降低感染风险,但感染德尔塔变体的已接种和未接种人群的病毒载量相似,这使得疫苗接种防止传播的程度受到质疑。
我们使用来自英格兰的接触者检测数据,对涉及 SARS-CoV-2 感染成年指数患者的成年接触者的回顾性观察队列研究进行了分析。我们使用多变量泊松回归来研究指数患者和接触者的疫苗接种状况与传播之间的关联,并确定这些关联如何随 B.1.1.7(阿尔法)和德尔塔变体以及第二次接种疫苗后的时间而变化。
在 108498 名指数患者的 146243 名接受检测的接触者中,54667 名(37%)的 SARS-CoV-2 聚合酶链反应(PCR)检测呈阳性。与未接种疫苗相比,在感染阿尔法变体的指数患者中,接种两剂 BNT162b2 或 ChAdOx1 nCoV-19(也称为 AZD1222)与接触者 PCR 阳性率降低独立相关(接种 BNT162b2 的调整后比值比为 0.32;95%置信区间 [CI],0.21 至 0.48;接种 ChAdOx1 nCoV-19 的调整后比值比为 0.48;95%CI,0.30 至 0.78)。与阿尔法变体相比,疫苗接种对德尔塔变体传播的减少作用较小,而接种两剂 BNT162b2 后对德尔塔变体传播的减少作用更大(与未接种疫苗相比的调整后比值比为 0.50;95%CI,0.39 至 0.65),而接种两剂 ChAdOx1 nCoV-19 后的减少作用较小(调整后比值比为 0.76;95%CI,0.70 至 0.82)。指数患者的循环阈值(Ct)值(提示病毒载量)的变化解释了两种变体疫苗接种相关传播减少的 7%至 23%。在第二次接种后,德尔塔变体的传播减少随着时间的推移而下降,到接种 ChAdOx1 nCoV-19 的指数患者的第 12 周,其传播水平与未接种疫苗者相似,而接种 BNT162b2 的指数患者的传播水平则大幅下降。接触者的保护作用也在第二次接种后 3 个月内下降。
与阿尔法变体相比,接种疫苗对德尔塔变体的传播减少作用较小,且效果随时间减弱。指数患者诊断时的 PCR Ct 值仅部分解释了传播减少。(由英国卫生部和其他部门资助)。