Multi-platform deep sequencing of SARS-CoV-2 JN.1 lineages variation reveal immune escape and transmission

Abstract Objectives Dominant strains had been replaced by SARS-CoV-2 JN.1 lineages, and spread widely in a short period of time. However, accurate detection method and reason for rapid spread have not been clarified. Methods Ion Torrent, Illumina and Nanopore sequencing platforms were used to detect whole genome sequences of SARS-CoV-2 positive cases in Dalian CDC from December 2023 to January 2024. Results Ion Torrent and Illumina platform had missing sites, but optimized Ion Torrent and Nanopore platform covered all detected sites. Ion Torrent platform had higher sensitivity than others and was more suitable for short-read length sequencing. However, primers need to be optimized in time. Illumina platform was also suitable for short-read length and prone to site drop out. Nanopore platform was more suitable for long read-length sequencing and had high compatibility for more variation site. Furthermore, compared JN.1 lineages with BA.2.86, multiple specific variation sites were detected for the first time in non-S protein region. Conclusion Timely optimized primers and supplement variation sites will provide a more effective mean for monitoring and controlling the prevalence of JN.1 lineages in advance, and the discovery of specific variation sites may reveal the reasons for immune escape and rapid transmission.