The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Background: Fast and effective methods are needed for sequencing the SARS-CoV-2 genome to track genetic mutations and identify new and emerging variants during the ongoing pandemic. Objective: Assess the performance of the SARS-CoV-2 AmpliSeq Research Panel and S5 plug-in analysis tools for whole genome sequence analysis of SARS-CoV-2 and compare the results to those obtained with the MiSeq based ARTIC analysis pipeline, using metrics such as depth, coverage, and concordance of single nucleotide variant (SNV) calls. Methods: A total of 191 clinical specimens and a single cultured isolate were extracted and sequenced with AmpliSeq technology and analysis tools. Of the 191 clinical specimens, 83 (Ct 15.58 – 32.54) were also sequenced using an Illumina MiSeq based method with the ARTIC analysis pipeline for a direct comparison. Results: 176 of the 191 clinical specimens sequenced on the S5XL and prepared using the SARS-CoV-2 Research Panel, had near complete coverage (>98%) of the viral genome, with an average depth of 5031x. Similar coverage (>98%) levels were observed for 81/83 primary specimens sequenced with both methods tested. The sample with the lowest viral load (Ct of 32.54) achieved 89% coverage using the MiSeq method and failed to sequence with the AmpliSeq method. Consensus sequences produced by each method were identical in 81/82 samples, in areas of equal coverage, with a single difference present in one sample. Conclusions: The AmpliSeq approach is as effective as the Illumina based method using ARTIC V3 amplification for sequencing SARS-CoV-2 direct from patient specimens across a range of viral loads (Ct 15.56-32.54, median = 22.18). The AmpliSeq workflow is very easily automated with the Ion Chef and S5 instruments and requires less training and experience with NGS preparation than the Illumina workflow.