Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study.
Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study.
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DOI：
10.1016/s1473-3099(21)00648-4
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发表时间：
2022-03
期刊：
影响因子：
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通讯作者：
ATACCC Study Investigators
中科院分区：
文献类型：
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作者：
Singanayagam A;Hakki S;Dunning J;Madon KJ;Crone MA;Koycheva A;Derqui-Fernandez N;Barnett JL;Whitfield MG;Varro R;Charlett A;Kundu R;Fenn J;Cutajar J;Quinn V;Conibear E;Barclay W;Freemont PS;Taylor GP;Ahmad S;Zambon M;Ferguson NM;Lalvani A;ATACCC Study Investigators
SARS-CoV-2 δ (B.1.617.2)变体具有高度传染性，并在全球传播，包括在疫苗接种率高的人群中传播。我们的目的是调查社区中接种疫苗和未接种疫苗的轻度丁型变异感染个体的传播和病毒载量动力学。在2020年9月13日至2021年9月15日期间，招募了471例英国COVID-19指数病例的602名社区接触者（通过英国合同追踪系统确定）参与COVID-19传播和传染性评估接触者队列研究，并在长达20天的每日采样中提供了8145份上呼吸道样本。年龄在5岁或以上的家庭和非家庭接触者如果能够提供知情同意并同意自行擦拭上呼吸道，则符合招募资格。我们通过接触162例与流行病学相关的三角洲变异体感染指数病例的231名接触者的疫苗接种状况分析了传播风险。我们比较了完全接种丁型病毒感染者（n=29）与未接种丁型病毒感染者（n=16）、α型病毒感染者（B.1.1.7; n=39）和前α型病毒感染者（n=49）的病毒载量轨迹。流行病学分析的主要结果是评估按接触者疫苗接种状况和指示病例疫苗接种状况分层的家庭接触者的继发发病率（SAR）。病毒载量动力学分析的主要结果是根据SARS-CoV-2变异和疫苗接种状况检测参与者之间病毒峰值载量、病毒生长速率和病毒下降速率的差异。在完全接种疫苗的个体中，暴露于delta变异的家庭接触者的SAR为25% (95% CI 18-33)，而在未接种疫苗的个体中为38%（24-53）。在完全接种接触者中，从第二次疫苗剂量到研究招募的中位数时间，感染者（中位数101天[IQR 74-120]）比未感染者（中位数64天[32-97]，p= 0.001）更长。暴露于完全接种的指示病例的家庭接触者的SAR与暴露于未接种指示病例的家庭接触者相似（接种疫苗者为25% [95% CI 15-35]，未接种疫苗者为23%[15-31]）。在完全接种疫苗的家庭接触者中，31例感染中有12例（39%）来自与流行病学相关的完全接种疫苗的指示病例，这一情况经3对指示病例-接触者的基因组学和病毒学分析进一步证实。虽然峰值病毒载量没有因接种状态或变异类型而异，但随着年龄的增长而适度增加（10岁和50岁之间每毫升log10病毒载量的差异为0.39[95%可信区间为- 0.03至0.79]）。与未接种疫苗的前α(0.69)、α(0.82)或δ(0.79)变异感染的个体相比，完全接种疫苗的δ变异感染个体的平均病毒载量下降速度（后验概率>.84）更快（0.95 log10拷贝/ mL / day）。在个体中，更快的病毒载量增长与更高的峰值病毒载量相关（相关性为0.42[95%可信区间为0.13 ~ 0.65]），与较慢的下降相关（相关性为- 0.44[95%可信区间为- 0.67 ~ - 0.18]）。疫苗接种可减少丁型病毒变异感染的风险，并加速病毒清除。尽管如此，完全接种疫苗的突破性感染个体的病毒载量峰值与未接种疫苗的病例相似，并且可以在家庭环境中有效地传播感染，包括传播给完全接种疫苗的接触者。宿主-病毒在感染早期的相互作用可能塑造整个病毒轨迹。国家健康研究所。
The SARS-CoV-2 delta (B.1.617.2) variant is highly transmissible and spreading globally, including in populations with high vaccination rates. We aimed to investigate transmission and viral load kinetics in vaccinated and unvaccinated individuals with mild delta variant infection in the community. Between Sept 13, 2020, and Sept 15, 2021, 602 community contacts (identified via the UK contract-tracing system) of 471 UK COVID-19 index cases were recruited to the Assessment of Transmission and Contagiousness of COVID-19 in Contacts cohort study and contributed 8145 upper respiratory tract samples from daily sampling for up to 20 days. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. We analysed transmission risk by vaccination status for 231 contacts exposed to 162 epidemiologically linked delta variant-infected index cases. We compared viral load trajectories from fully vaccinated individuals with delta infection (n=29) with unvaccinated individuals with delta (n=16), alpha (B.1.1.7; n=39), and pre-alpha (n=49) infections. Primary outcomes for the epidemiological analysis were to assess the secondary attack rate (SAR) in household contacts stratified by contact vaccination status and the index cases’ vaccination status. Primary outcomes for the viral load kinetics analysis were to detect differences in the peak viral load, viral growth rate, and viral decline rate between participants according to SARS-CoV-2 variant and vaccination status. The SAR in household contacts exposed to the delta variant was 25% (95% CI 18–33) for fully vaccinated individuals compared with 38% (24–53) in unvaccinated individuals. The median time between second vaccine dose and study recruitment in fully vaccinated contacts was longer for infected individuals (median 101 days [IQR 74–120]) than for uninfected individuals (64 days [32–97], p=0·001). SAR among household contacts exposed to fully vaccinated index cases was similar to household contacts exposed to unvaccinated index cases (25% [95% CI 15–35] for vaccinated vs 23% [15–31] for unvaccinated). 12 (39%) of 31 infections in fully vaccinated household contacts arose from fully vaccinated epidemiologically linked index cases, further confirmed by genomic and virological analysis in three index case–contact pairs. Although peak viral load did not differ by vaccination status or variant type, it increased modestly with age (difference of 0·39 [95% credible interval –0·03 to 0·79] in peak log10 viral load per mL between those aged 10 years and 50 years). Fully vaccinated individuals with delta variant infection had a faster (posterior probability >0·84) mean rate of viral load decline (0·95 log10 copies per mL per day) than did unvaccinated individuals with pre-alpha (0·69), alpha (0·82), or delta (0·79) variant infections. Within individuals, faster viral load growth was correlated with higher peak viral load (correlation 0·42 [95% credible interval 0·13 to 0·65]) and slower decline (–0·44 [–0·67 to –0·18]). Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts. Host–virus interactions early in infection may shape the entire viral trajectory. National Institute for Health Research.