Large Scale SARS-CoV-2 Molecular Testing and Genomic Surveillance Reveal Prolonged Infections, Protracted RNA shedding, and Viral Reinfections.
Large Scale SARS-CoV-2 Molecular Testing and Genomic Surveillance Reveal Prolonged Infections, Protracted RNA shedding, and Viral Reinfections.
复制标题
DOI：
10.3389/fcimb.2022.809407
复制
发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
大规模 SARS-CoV-2 分子检测与诊断实验室的全基因组测序相结合，有助于实时基因组监测。广泛的基因组、实验室和临床数据为了解再感染与长期 RNA 脱落和长期感染的病例提供了宝贵的资源。在这项研究中，使用了2020年3月11日至2021年9月23日期间在约翰霍普金斯大学临床病毒学实验室经SARS-CoV-2分子诊断呈阳性的总共22,292份临床标本的数据，用于识别具有两个或多个阳性结果的患者。从首次阳性结果起长达 403 天的时间范围内，从 1,529 名患者中收集了总共 3,650 个样本，这些样本的阳性结果在 2 到 20 之间。 1,622 个样本有周期阈值 (Ct)，首次呈阳性后 11 天，其中位数超过 30。在免疫功能低下的患者中首次呈阳性后，感染性病毒在细胞培养物中的恢复时间长达 70 天。作为 SARS-CoV-2 基因组监测的一部分，生成的全基因组测序数据可用于来自多次检测呈阳性的患者的 1,027 个样本。在最初呈阳性后 10 天以上收集的高质量序列（覆盖率 >90% 且平均深度 >100）的阳性样本更有可能来自未接种疫苗或免疫抑制的患者。 3 名患者在先前感染不同病毒分支 130 多天后再次感染了相关病毒变种。在 75 名拥有 2 个或更多高质量序列的患者中，获得更多替换或缺失与缺乏疫苗接种以及恢复病毒之间的时间较长有关。我们的研究强调了整合基因组、实验室和临床数据对于了解 SARS-CoV-2 生物学以及为未来流行病和大流行树立先例的价值。
Large-scale SARS-CoV-2 molecular testing coupled with whole genome sequencing in the diagnostic laboratories is instrumental for real-time genomic surveillance. The extensive genomic, laboratory, and clinical data provide a valuable resource for understanding cases of reinfection versus prolonged RNA shedding and protracted infections. In this study, data from a total of 22,292 clinical specimens, positive by SARS-CoV-2 molecular diagnosis at Johns Hopkins clinical virology laboratory between March 11th 2020 to September 23rd 2021, were used to identify patients with two or more positive results. A total of 3,650 samples collected from 1,529 patients who had between 2 and 20 positive results were identified in a time frame that extended up to 403 days from the first positive. Cycle threshold values (Ct) were available for 1,622 samples, the median of which was over 30 by 11 days after the first positive. Extended recovery of infectious virus on cell culture was notable for up to 70 days after the first positive in immunocompromised patients. Whole genome sequencing data generated as a part of our SARS-CoV-2 genomic surveillance was available for 1,027 samples from patients that had multiple positive tests. Positive samples collected more than 10 days after initial positive with high quality sequences (coverage >90% and mean depth >100), were more likely to be from unvaccinated, or immunosuppressed patients. Reinfections with viral variants of concern were found in 3 patients more than 130 days from prior infections with a different viral clade. In 75 patients that had 2 or more high quality sequences, the acquisition of more substitutions or deletions was associated with lack of vaccination and longer time between the recovered viruses. Our study highlights the value of integrating genomic, laboratory, and clinical data for understanding the biology of SARS-CoV-2 as well as for setting a precedent for future epidemics and pandemics.