ARTICLES| VOLUME 4, ISSUE 8, E632-E641, AUGUST 2023Download Full Issue

Viral and antibody dynamics of acute infection with SARS-CoV-2 omicron variant (B.1.1.529): a prospective cohort study from Shenzhen, China

Yang Yang, Liping Guo, Jing Yuan, et al

Lancet Microbe 2023; 8: E632-E641 Published:July 14, 2023 DOI:https://doi.org/10.1016/S2666-5247(23)00139-8

Summary

Background

Elucidating viral dynamics within the host is important for designing public health measures against SARS-CoV-2, particularly during the early stages of infection when transmission potential rapidly increases. We aimed to analyse the viral and antibody dynamics of the omicron variant in relation to symptom onset or laboratory confirmation and replication dynamics throughout the infection course.

阐明 SARS-CoV-2 在感染宿主体内(特别是在传播能力迅速增加的感染初期)的复制动力学， 对于制定有效的、针对性的公共卫生措施至关重要。因此，本研究统分析了与发病天数以及 实验确诊天数相关的病毒和抗体动力学，以及 SARS-CoV-2 在整个感染过程的复制动力学。

Methods

In this prospective cohort study, patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to Shenzhen Third People's Hospital (Shenzhen, China) between Jan 11, 2020, and April 24, 2022, were screened for eligibility. We included immunocompetent individuals with acute SARS-CoV-2 infection without antiviral agents targeting SARS-CoV-2. Serial nasopharyngeal swabs and plasma samples were analysed for viral RNAs and specific IgG antibodies of SARS-CoV-2. The comparative viral and antibody kinetics in association with symptom onset or laboratory confirmation and replication dynamics throughout the infection course were calculated by the locally estimated scatterplot smoothing curve fitting polynomial regression. The associations between viral and antibody dynamics and vaccination, age, sex, disease severity, and underlying health conditions were analysed using the Mann-Whitney U test and the Gehan-Breslow-Wilcoxon method.

在这项前瞻性队列研究中，我们对 2020 年 1 月 11 日至 2022 年 4 月 24 日期间在深圳市第三 人民医院(中国深圳)住院的 SARS-CoV-2 确诊感染患者进行了筛选，然后纳入了免疫功能 正常、未使用 SARS-CoV-2 靶向抗病毒药物治疗的急性期感染患者。我们采集系列鼻咽拭子 和血浆样本，检测了 SARS-CoV-2 病毒 RNA 和特异性 IgG 抗体，然后采用局部多项式回归 拟合计算并比较了与发病天数或者实验室确诊天数相关病毒和抗体动力学，以及病毒在整个 感染过程中的复制动力学。使用 Mann-Whitney U 检验和 Gehan-Breslow-Wilcoxon 方法分析 病毒和抗体动力学与疫苗接种、年龄、性别、疾病严重程度和基础健康状况之间的关联。

Findings

15 406 serial nasopharyngeal swabs and 2324 plasma samples were taken from 2043 individuals with acute SARS-CoV-2 infection (n=217 prototype [A.1] and D614G [B.1] variant [wild-type]; n=105 delta variant [B.1.617.2]; n=1721 omicron variant [B.1.1.529]) and were included for the analyses. The mean Ct value of omicron variant on the first day post symptom onset (dpo; defined as the first day post laboratory confirmation in asymptomatic participants) was 22·65 (95% CI 22·05–23·26). Peak viral load was reached with a mean Ct value of 17·63 (17·47–17·79) at a mean of 3·19 dpo (95% CI 3·09–3·28), and viral clearance (Ct values ≥35) was reached at a mean of 13·50 dpo (95% CI 13·32–13·67). Omicron variant showed faster viral replication and clearance than wild-type SARS-CoV-2 and delta variant, and the viral load at the first dpo and the peak viral load was lower than delta variant but higher than wild-type SARS-CoV-2. Age, sex, disease severity, and underlying health conditions were associated with the viral dynamics of omicron variant, with faster viral clearance found in young (aged 0–14 years), male, and asymptomatic participants, and those without underlying health conditions. Replication dynamics thoughout the infection course showed that peak viral load was reached at a mean of 5·06 dpo (4·76–5·36) and viral clearance took a mean of 14·27 days (13·6–14·93) for omicron variant. SARS-CoV-2-specific IgG increased earlier and faster to significantly higher concentrations in breakthrough infection than naive infection with omicron variant, despite long intervals (≥7 months) between the last dose of vaccination and infection.

本研究纳入并分析了采集自 2,043 例 SARS-CoV-2 急性期感染者(原型株[A.1])和 D614G 突变株[B.1]，N=217;Delta 突变株[B.1.617.2]，N =105;Omicron 突变株[B.1.1.529]，N =1721) 的 15406 个鼻咽拭子样本和 2324 个血浆样本检测结果。Omicron 突变株感染患者在发病第 一天(无症状感染者确诊当天定义为发病第 1 天)的平均 Ct 值为 22.65(95%置信区间:22.05 ~ 23.26)，平均需要 3.19 天(95%置信区间:3.09 ~ 3.28)达到峰值病毒载量(平均 Ct 值 17.63，95%置信区间:17.47 ~ 17.79)，平均需要 13.50 天(95%置信区间:13.32 ~ 13.67) 达到病毒清除病毒标准(Ct 值≥35)。与野生型毒株和 Delta 突变株相比，Omicron 突变株 复制更快、病毒清除时间更短，其发病第 1 天和峰值病毒载量均低于 Delta 突变株，但均高 于野生型毒株。年龄、性别、疾病严重程度和基础疾病与 Omicron 突变株的病毒动力学相关， 在儿童(0 ~ 14 岁)、男性、无症状和无基础疾病的患者中病毒清除速度更快。整个感染过 程的病毒动力学分析结果显示，Omicron 突变株感染后平均需要 5.06 天(95%置信区间:4.76~ 5.36)达到峰值病毒载量，平均 14.27 天(95%置信区间:13.6 ~ 14.93)达到病毒清除标 准。抗体动力学分析结果显示，与未接种疫苗的感染者相比，即使最后一针疫苗的接种时间 与感染时间的间隔超过 7 个月，Omicron 突变株突破感染者体内 SARS-CoV-2 特异性抗体产 生的更早、更快，达到的峰值更高。

Interpretation

Our data provide a comprehensive overview of the longitudinal viral and antibody dynamics of omicron variant in people with acute SARS-CoV-2 infection, with important implications for public health strategies, including population screening, antiviral treatment, isolation periods, and vaccination.

本研究全面解析了 SARS-CoV-2 Omicron 突变株急性感染期的病毒和抗体动力学特征，研究 结果对制定人群筛查、抗病毒治疗、隔离期和疫苗接种等公共卫生策略具有重要意义。

Funding

National Natural Science Foundation of China and Emergency Key Program of Guangzhou Laboratory.

Translation

For the Chinese translation of the abstract see Supplementary Materials section.