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利用大鼠冠状病毒相关脱落和传播来模拟 SARS-CoV-2 的传播。

Modeling SARS-CoV-2 propagation using rat coronavirus-associated shedding and transmission.

机构信息

Department of Comparative Medicine, Yale School of Medicine, New Haven, CT, United States of America.

Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States of America.

出版信息

PLoS One. 2021 Nov 23;16(11):e0260038. doi: 10.1371/journal.pone.0260038. eCollection 2021.

Abstract

At present, global immunity to SARS-CoV-2 resides within a heterogeneous combination of susceptible, naturally infected and vaccinated individuals. The extent to which viral shedding and transmission occurs on re-exposure to SARS-CoV-2 is an important determinant of the rate at which COVID-19 achieves endemic stability. We used Sialodacryoadenitis Virus (SDAV) in rats to model the extent to which immune protection afforded by prior natural infection via high risk (inoculation; direct contact) or low risk (fomite) exposure, or by vaccination, influenced viral shedding and transmission on re-exposure. On initial infection, we confirmed that amount, duration and consistency of viral shedding, and seroconversion rates were correlated with exposure risk. Animals were reinfected after 3.7-5.5 months using the same exposure paradigm. 59% of seropositive animals shed virus, although at lower amounts. Previously exposed seropositive reinfected animals were able to transmit virus to 25% of naive recipient rats after 24-hour exposure by direct contact. Rats vaccinated intranasally with a related virus (Parker's Rat Coronavirus) were able to transmit SDAV to only 4.7% of naive animals after a 7-day direct contact exposure, despite comparable viral shedding. Cycle threshold values associated with transmission in both groups ranged from 29-36 cycles. Observed shedding was not a prerequisite for transmission. Results indicate that low-level shedding in both naturally infected and vaccinated seropositive animals can propagate infection in susceptible individuals. Extrapolated to COVID-19, our results suggest that continued propagation of SARS-CoV-2 by seropositive previously infected or vaccinated individuals is possible.

摘要

目前,全球对 SARS-CoV-2 的免疫力存在于易感人群、自然感染者和接种疫苗者的异质组合中。重新接触 SARS-CoV-2 时病毒脱落和传播的程度是 COVID-19 达到地方性稳定的速度的重要决定因素。我们使用大鼠唾液腺炎病毒(SDAV)来模拟先前通过高风险(接种;直接接触)或低风险(媒介物)暴露自然感染或接种疫苗所提供的免疫保护在重新暴露时对病毒脱落和传播的影响。在初次感染时,我们证实了病毒脱落的量、持续时间和一致性以及血清转化率与暴露风险相关。在使用相同暴露模式 3.7-5.5 个月后,动物再次感染。59%的血清阳性动物出现病毒脱落,但脱落量较低。先前接触过的血清阳性再感染动物在 24 小时直接接触后能够将病毒传播给 25%的未感染受体大鼠。用相关病毒(帕克大鼠冠状病毒)鼻内接种疫苗的大鼠在 7 天的直接接触暴露后仅能将 SDAV 传播给 4.7%的未感染动物,尽管病毒脱落量相当。两组中与传播相关的循环阈值值范围为 29-36 个循环。观察到的脱落不是传播的先决条件。结果表明,自然感染和接种疫苗的血清阳性动物中低水平的脱落可以在易感个体中传播感染。从 COVID-19 推断,我们的结果表明,血清阳性的先前感染或接种疫苗的个体继续传播 SARS-CoV-2 是可能的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa5f/8610237/21b0aeffc8bd/pone.0260038.g001.jpg

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