Analyzing the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from clinical samples is crucial for understanding viral spread and evolution as well as for vaccine development. Existing RNA sequencing methods are demanding on user technique and time and, thus, not ideal for time-sensitive clinical samples; these methods are also not optimized for high performance on viral genomes. We developed a facile, practical, and robust approach for metagenomic and deep viral sequencing from clinical samples. We demonstrate the utility of our approach on pharyngeal, sputum, and stool samples collected from coronavirus disease 2019 (COVID-19) patients, successfully obtaining whole metatranscriptomes and complete high-depth, high-coverage SARS-CoV-2 genomes with high yield and robustness. With a shortened hands-on time from sample to virus-enriched sequencing-ready library, this rapid, versatile, and clinic-friendly approach will facilitate molecular epidemiology studies during current and future outbreaks.

从临床样本中分析严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的基因组对于理解病毒的传播和进化以及疫苗开发至关重要。现有的RNA测序方法需要用户技术和时间，因此对于时间敏感的临床样品而言并不理想；这些方法也没有针对病毒基因组的高性能进行优化。我们为临床样品的宏基因组学和深度病毒测序开发了一种简便，实用且强大的方法。我们展示了我们的方法在从冠状病毒病2019（COVID-19）患者收集的咽，痰和粪便样品中的效用，成功获得了完整的转录组和完整，高产量，高覆盖率的SARS-CoV-2基因组。健壮性。