Lane Gregory, Zhou Guangyu, Hultquist Judd F, Simons Lacy M, Redondo Ramon Lorenzo-, Ozer Egon A, McCarthy Danielle M, Ison Michael G, Achenbach Chad J, Wang Xinkun, Wai Ching Man, Wyatt Eugene, Aalsburg Alan, Yang Qiaohan, Noto Torben, Alisoltani Arghavan, Ysselstein Daniel, Awatramani Rajeshwar, Murphy Robert, Theron Grant, Zelano Christina
medRxiv. 2023 Sep 8:2023.09.06.23295138. doi: 10.1101/2023.09.06.23295138.
SARS-CoV-2 is spread through exhaled breath of infected individuals. A fundamental question in understanding transmission of SARS-CoV-2 is how much virus an individual is exhaling into the environment while they breathe, over the course of their infection. Research on viral load dynamics during COVID-19 infection has focused on internal swab specimens, which provide a measure of viral loads inside the respiratory tract, but not on breath. Therefore, the dynamics of viral shedding on exhaled breath over the course of infection are poorly understood. Here, we collected exhaled breath specimens from COVID-19 patients and used RTq-PCR to show that numbers of exhaled SARS-CoV-2 RNA copies during COVID-19 infection do not decrease significantly until day 8 from symptom-onset. COVID-19-positive participants exhaled an average of 80 SARS-CoV-2 viral RNA copies per minute during the first 8 days of infection, with significant variability both between and within individuals, including spikes over 800 copies a minute in some patients. After day 8, there was a steep drop to levels nearing the limit of detection, persisting for up to 20 days. We further found that levels of exhaled viral RNA increased with self-rated symptom-severity, though individual variation was high. Levels of exhaled viral RNA did not differ across age, sex, time of day, vaccination status or viral variant. Our data provide a fine-grained, direct measure of the number of SARS-CoV-2 viral copies exhaled per minute during natural breathing-including 312 breath specimens collected multiple times daily over the course of infection-in order to fill an important gap in our understanding of the time course of exhaled viral loads in COVID-19.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)通过感染者呼出的气体传播。理解SARS-CoV-2传播的一个基本问题是,个体在感染过程中呼吸时会向环境中呼出多少病毒。关于2019冠状病毒病(COVID-19)感染期间病毒载量动态的研究主要集中在内拭子样本上,这些样本提供了呼吸道内病毒载量的测量值,但未关注呼出气体。因此,人们对感染过程中呼出气体中病毒脱落的动态了解甚少。在这里,我们收集了COVID-19患者的呼出气体样本,并使用逆转录定量聚合酶链反应(RTq-PCR)表明,COVID-19感染期间呼出的SARS-CoV-2 RNA拷贝数直到症状出现后的第8天才显著下降。COVID-19阳性参与者在感染的前8天平均每分钟呼出80个SARS-CoV-2病毒RNA拷贝,个体之间和个体内部均存在显著差异,包括一些患者每分钟超过800个拷贝的峰值。在第8天之后,病毒载量急剧下降至接近检测限的水平,并持续长达20天。我们进一步发现,呼出病毒RNA的水平随着自我评估的症状严重程度而增加,尽管个体差异很大。呼出病毒RNA的水平在年龄、性别、一天中的时间、疫苗接种状态或病毒变体方面没有差异。我们的数据提供了在自然呼吸过程中每分钟呼出的SARS-CoV-2病毒拷贝数的精细、直接测量值——包括在感染过程中每天多次收集的312份呼出气体样本——以填补我们对COVID-19呼出病毒载量时间进程理解上的一个重要空白。