The sequencing of SARS-CoV-2 provides essential information on viral evolution, transmission, and epidemiology. In this paper, we performed the whole-genome sequencing of SARS-CoV-2 using nanopore and Illumina sequencing to describe the circulation of the virus lineages in Armenia. The analysis of 145 full genomes identified six clades (19A, 20A, 20B, 20I, 21J, and 21K) and considerable intra-clade PANGO lineage diversity. Phylodynamic and transmission analysis allowed to attribute specific clades as well as infer their importation routes. Thus, the first two waves of positive case increase were caused by the 20B clade, the third peak caused by the 20I (Alpha), while the last two peaks were caused by the 21J (Delta) and 21K (Omicron) variants. The functional analyses of mutations in sequences largely affected epitopes associated with protective HLA loci and did not cause the loss of the signal in PCR tests targeting ORF1ab and N genes as confirmed by RT-PCR. We also compared the performance of nanopore and Illumina short-read sequencing and showed the utility of nanopore sequencing as an efficient and affordable alternative for large-scale molecular epidemiology research. Thus, our paper describes new data on the genomic diversity of SARS-CoV-2 variants in Armenia in the global context of the virus molecular genomic surveillance.

Sequencing of SARS-CoV-2 provides essential information into viral evolution, transmission, and epidemiology. Short-read next-generation sequencing platforms are currently the gold-standard approaches characterized by the highest accuracy. Meanwhile, Oxford Nanopore's long-read sequencing devices show great promise, offering comparable accuracy, fast turnaround time, and reduced cost. In this study, we performed whole-genome sequencing and molecular-genetic characterization of SARS-CoV-2 from clinical specimens using an amplicon-based nanopore sequencing approach. Lineage and phylogenetic analysis identified the most prevalent lineages at different time points (B.1.1.163, B.1.1.208, B.1.1, and since March 2021 - B.1.1.7). In addition, we evaluated the possible effect of identified mutations on the efficacy of recommended primers and probes used for PCR detection of SARS-CoV-2. In summary, a high-quality SARS-CoV-2 genome can be acquired by nanopore sequencing and it can serve as an efficient and affordable alternative to short-read next-generation sequencing and be used for epidemiologic surveillance and molecular-genetic analyses of the virus.

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