WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, New Territories, Hong Kong Special Administrative Region, China.
Lancet Microbe. 2023 Sep;4(9):e722-e731. doi: 10.1016/S2666-5247(23)00146-5.
Assessment of viral kinetics of SARS-CoV-2 can inform on host immune responses to the virus and on the viral transmission potential. We aimed to characterise viral shedding kinetics by age, virus type, and clinical outcome, and to examine the potential effect of vaccination on viral shedding.
In this retrospective observational study, we analysed longitudinal data on cycle threshold (Ct) values of reverse-transcription quantitative PCR (RT-qPCR) assays of upper respiratory tract samples from symptomatic patients with COVID-19. Patients who were confirmed with COVID-19 with at least one Ct value of the RT-qPCR test available within 28 days after symptom onset, and discharged or died at the time of the analysis, were included in the study. Patients were isolated in hospitals in Hong Kong during three major epidemic waves dominated by the ancestral strain or omicron BA.2. We modelled the temporal trajectories of viral burden in these patients. Electronic medical records of the patients with COVID-19 were retrieved and linked to the patients' epidemiological information obtained from contact tracing. Patients who were infected outside Hong Kong, infected with variants other than the ancestral strain or omicron BA.2, not reporting any COVID-19 related symptoms, still hospitalised at the time of analysis, missing information on age, time of symptom onset, infection severity, vaccination or clinical outcome, infected more than once, or treated with nirmatrelvir-ritonavir or molnupiravir were excluded from analysis. The main outcome of this study is the temporal change of SARS-CoV-2 viral burden measured by Ct values of RT-qPCR tests in symptomatic patients with COVID-19.
Among 22 461 symptomatic patients with COVID-19 confirmed from July 1, 2020, to May 22, 2022, the estimated viral burden from a random-effects model indicated a longer duration of viral shedding in patients with more severe outcomes of infection (mean difference 13·1 days, 95% CI 12·9-13·3, for fatal vs mild-to-moderate) and in older patients (5·2, 5·0-5·5, for age ≥80 years vs 0-18 years). Vaccinated individuals with a breakthrough infection with the omicron BA.2 variant had a generally lower viral burden and shorter durations of viral shedding (mean difference of 2-4 days) over 4 weeks after onset than unvaccinated individuals infected with omicron BA.2, particularly in patients whose last dose of COVID-19 vaccine was received ≤90 days before symptom onset. Marginal differences in viral burden following symptom onset and the duration of viral shedding were observed between unvaccinated individuals infected with the ancestral strain and omicron BA.2.
The viral kinetics since symptom onset characterised for symptomatic patients with COVID-19 in our study show that previously vaccinated or younger individuals, or those with a milder infection, shed fewer viruses in a shorter period, implying possible transmission dynamics of SARS-CoV-2 and protective mechanisms of vaccination against infection and severe outcomes.
Hong Kong Health and Medical Research Fund and Hong Kong Collaborative Research Fund.
评估 SARS-CoV-2 的病毒动力学可以了解宿主对病毒的免疫反应和病毒传播潜力。我们旨在根据年龄、病毒类型和临床结局描述病毒脱落动力学,并研究疫苗接种对病毒脱落的潜在影响。
在这项回顾性观察研究中,我们分析了有症状的 COVID-19 患者上呼吸道样本的逆转录定量 PCR(RT-qPCR)检测的 Ct 值的纵向数据。研究纳入了至少有一次 RT-qPCR 检测 Ct 值在症状出现后 28 天内的 COVID-19 确诊患者,且在分析时已出院或死亡。患者在香港的医院进行隔离,在三次主要的疫情浪潮中,以原始株或 omicron BA.2 为主导。我们对这些患者的病毒载量的时间轨迹进行建模。检索 COVID-19 患者的电子病历,并与通过接触者追踪获得的患者流行病学信息相关联。我们排除了以下患者:在香港以外感染的患者、感染原始株或 omicron BA.2 以外的变异株的患者、未报告任何 COVID-19 相关症状的患者、仍在住院的患者、年龄、症状出现时间、感染严重程度、疫苗接种或临床结局、感染超过一次、接受 nirmatrelvir-ritonavir 或 molnupiravir 治疗的患者以及信息缺失的患者。本研究的主要结局是通过 RT-qPCR 检测的 Ct 值测量的有症状的 COVID-19 患者的 SARS-CoV-2 病毒载量的时间变化。
在 2020 年 7 月 1 日至 2022 年 5 月 22 日期间确诊的 22461 例有症状的 COVID-19 患者中,随机效应模型估计的病毒载量表明,感染结局更严重的患者(平均差异 13.1 天,95%CI 12.9-13.3,死亡 vs 轻度至中度)和年龄较大的患者(5.2 天,5.0-5.5 岁)的病毒脱落持续时间更长。接种疫苗且 omicron BA.2 突破性感染的个体在发病后 4 周内的病毒载量通常较低,病毒脱落持续时间较短(2-4 天),与 omicron BA.2 感染的未接种疫苗个体相比,尤其是在最后一剂 COVID-19 疫苗接种时间在症状出现前 90 天内的患者中。在症状出现后和病毒脱落持续时间方面,未接种疫苗的原始株感染患者与 omicron BA.2 感染患者之间观察到病毒载量的微小差异。
我们研究中对有症状的 COVID-19 患者的症状出现后病毒动力学特征表明,先前接种疫苗或年龄较小的个体,或感染较轻的个体,在较短的时间内脱落较少的病毒,这可能反映了 SARS-CoV-2 的传播动态和疫苗接种对感染和严重结局的保护机制。
香港卫生与医学研究基金和香港联合研究基金。