Genomic monitoring of SARS-CoV-2 uncovers rare in-frame deletion in ORF1a (nsp3) gene: A case report

Genetic changes in emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may compromise the effectiveness of laboratory methods used to detect SARS-CoV-2 for the purposes of public health surveillance. We described a case involving a 40-year-old vaccinated male with RT-qPCR-confirmed symptomatic COVID-19 (fever, chills, cough, and headache) whose nasal specimen was collected during routine genomic surveillance; no hospitalization or complications were reported, and therapeutic interventions were not evaluated as part of this surveillance activity. A rare in-frame deletion in the open reading frame 1a (ORF1a) gene was identified using next-generation sequencing on the GridION platform. Sequence data were assembled and analyzed using the Theiagen workflows on the Terra platform. Genome annotation revealed a 69-nucleotide deletion within the non-structural protein 3 (nsp3) of ORF1a. This deletion was identified in only 22 additional SARS-CoV-2 sequences available in GISAID. This newly discovered genetic alteration may have implications for understanding viral biology, including transmission and virulence. These findings highlight the importance of characterizing the functional consequences of rare genomic deletions and evaluating their potential impact on molecular assay performance and genomic surveillance.