NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK; Department of Infectious Disease, Imperial College London, London, UK; National Infection Service, Public Health England, London, UK.
NIHR Health Protection Research Unit in Respiratory Infections, National Heart and Lung Institute, Imperial College London, London, UK.
Lancet Infect Dis. 2022 Feb;22(2):183-195. doi: 10.1016/S1473-3099(21)00648-4. Epub 2021 Oct 29.
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 log 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 log 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.
SARS-CoV-2 的 delta(B.1.617.2)变体具有高度传染性,并在包括高疫苗接种率人群在内的全球范围内传播。我们旨在研究社区中轻度 delta 变体感染的已接种和未接种人群中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,从 471 例英国 COVID-19 索引病例中招募了 602 名社区接触者(通过英国接触者追踪系统确定),并将其纳入 COVID-19 接触者传染性和传染性评估研究队列。在 20 天内,从每天的上呼吸道样本中采集了 8145 个样本。如果 5 岁或以上的家庭和非家庭接触者能够提供知情同意并同意自我拭子取样,则有资格招募。我们分析了 231 名接触 162 例与 delta 变体感染的传染性相关的索引病例的接触者的疫苗接种状况的传播风险。我们比较了 29 名完全接种疫苗的 delta 感染个体与 16 名未接种疫苗的 delta、alpha(B.1.1.7;39 名)和 pre-alpha(49 名)感染个体的病毒载量轨迹。流行病学分析的主要结果是评估按家庭接触者疫苗接种状况和索引病例疫苗接种状况分层的家庭接触者的二次攻击率(SAR)。病毒载量动力学分析的主要结果是根据 SARS-CoV-2 变体和疫苗接种状况检测参与者峰值病毒载量、病毒增长率和病毒下降率的差异。
与未接种疫苗的个体(38%[24-53])相比,暴露于 delta 变体的家庭接触者中完全接种疫苗的个体的 SAR 为 25%(95%CI 18-33)。完全接种接触者中感染个体的第二剂疫苗接种后至研究招募的中位时间(中位数 101 天[IQR 74-120])长于未感染个体(中位数 64 天[32-97],p=0.001)。与接触完全接种疫苗的索引病例的家庭接触者相比,与接触未接种疫苗的索引病例的家庭接触者的 SAR 相似(接种疫苗者为 25%[15-35],未接种疫苗者为 23%[15-31])。完全接种疫苗的家庭接触者中有 31 例感染(39%)是由完全接种的具有传染性的相关索引病例引起的,在三对索引病例-接触者中通过基因组和病毒学分析进一步证实了这一点。尽管病毒载量峰值不因疫苗接种状况或变体类型而异,但它随着年龄的增长而略有增加(在 10 岁和 50 岁之间的峰值对数病毒载量中相差 0.39[95%可信区间 0.03-0.79])。与 pre-alpha(0.69)、alpha(0.82)或 delta(0.79)变体感染的未接种疫苗个体相比,感染 delta 变体的完全接种个体的病毒载量下降速度更快(后验概率>0.84)(每天病毒载量下降 0.95 对数拷贝/mL)。在个体内部,病毒载量增长较快与峰值病毒载量较高相关(相关性 0.42[95%可信区间 0.13-0.65]),与下降较慢相关(-0.44[-0.67 至-0.18])。
接种疫苗可降低 delta 变体感染的风险并加速病毒清除。尽管如此,突破性感染的完全接种个体的峰值病毒载量与未接种个体相似,并且可以在家庭环境中有效传播感染,包括传播给完全接种疫苗的接触者。感染早期的宿主-病毒相互作用可能会影响整个病毒轨迹。
英国国家卫生研究所。