Genomic and Temporal Analysis of Deletions Correlated to qRT-PCR Dropout in N Gene in Alpha, Delta and Omicron Variants

Abstract

Since the first SARS-CoV-2 outbreak, mutations such as single nucleotide polymorphisms (SNPs) and insertion/deletions (INDELs) have changed and characterized the viral genome sequence, structure and protein folding leading to the onset of new variants. The presence of those alterations challenges not only the clinical field but also the diagnostic demand due to failures in gene detection or incompleteness of polymerase chain reaction (PCR) results. In particular, the analysis of understudied genes such as N and the investigation through whole-genome next generation sequencing (WG-NGS) of regions more prone to mutate can help in the identification of new or reacquired mutations, with the aim of designing robust and long-lasting primers. In 48 samples of SARS-CoV-2 (including Alpha, Delta and Omicron variants), a lack of N gene amplification was observed in the genomes analyzed through WG-NGS. Three gene regions were detected hosting the highest number of SNPs and INDELs. In several cases, the latter can interfere deeply with both the sensitivity of diagnostic methodologies and the final protein folding. The monitoring over time of the viral evolution and the reacquisition among different variants of the same mutations or different alterations within the same genomic positions can be relevant to avoid unnecessary consumption of resources.

Editorial for SARS-CoV-2 and COVID-19 Topical Collection

“…The next section of the Topical Collection focuses on SARS-CoV-2 evolution and contains two review articles describing the evolution of the SARS-CoV-2 Omicron VoC and the genetic impact on viral fitness (43) and the Spike protein of the new SARS-CoV-2 VoCs (44). This section also includes two brief reports on the genomic and temporal analysis of deletions in the nucleocapsid (N) gene of the SARS-CoV-2 Omicron VoC and their correlation with qRT-PCR dropout (45), and the evolution and immune escape mutations in the S gene present in mild or moderate COVID-19 patients treated with monoclonal antibodies (46). Finally, a total of twelve original research articles are included in this part of the Topical Collection, describing different aspects of the evolution of SARS-CoV-2 (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58).…”