A Repeat Pattern of Founder Events for SARS-CoV-2 Variants in Alaska.

Alaska is a unique US state because of its large size, geographically disparate population density, and physical distance from the contiguous United States. Here, we describe a pattern of SARS-CoV-2 variant emergence across Alaska reflective of these differences. Using genomic data, we found that in Alaska, the Omicron sublineage BA.2.3 overtook BA.1.1 by the week of 27 February 2022, reaching 48.5% of sequenced cases. On the contrary, in the contiguous United States, BA.1.1 dominated cases for longer, eventually being displaced by BA.2 sublineages other than BA.2.3. BA.2.3 only reached a prevalence of 10.9% in the contiguous United States. Using phylogenetics, we found evidence of potential origins of the two major clades of BA.2.3 in Alaska and with logistic regression estimated how it emerged and spread throughout the state. The combined evidence is suggestive of founder events in Alaska and is reflective of how Alaska's unique dynamics influence the emergence of SARS-CoV-2 variants.

Pattern of SARS-CoV-2 variant B.1.1.519 emergence in Alaska.

Alaska has the lowest population density in the United States (US) with a mix of urban centers and isolated rural communities. Alaska's distinct population dynamics compared to the contiguous US may have contributed to unique patterns of SARS-CoV-2 variants observed in early 2021. Here we examined 2323 SARS-CoV-2 genomes from Alaska and 278,635 from the contiguous US collected from December 2020 through June 2021 because of the notable emergence and spread of lineage B.1.1.519 in Alaska. We found that B.1.1.519 was consistently detected from late January through June of 2021 in Alaska with a peak prevalence in April of 77.9% unlike the rest of the US at 4.6%. The earlier emergence of B.1.1.519 coincided with a later peak of Alpha (B.1.1.7) compared to the contiguous US. We also observed differences in variant composition over time between the two most populated regions of Alaska and a modest increase in COVID-19 cases during the peak incidence of B.1.1.519. However, it is difficult to disentangle how social dynamics conflated changes in COVID-19 during this time. We suggest that the viral characteristics, such as amino acid substitutions in the spike protein, likely contributed to the unique spread of B.1.1.519 in Alaska.

Identification of a novel SARS-CoV-2 variant with a truncated protein in ORF8 gene by next generation sequencing.

Using next generation sequencing technology, we identified a novel SARS-CoV-2 variant with a truncated ORF8 protein mutation near the end of the viral genome from nucleotides 27,878 to 27,958. This point mutation from C to T at nucleotide 27,956 changed the amino acid codon CAA (glutamine) to a stop codon, TAA, created a novel stop codon in ORF8 gene, resulting in a much smaller ORF8 protein (26 aa) than the wild type ORF8 protein (121 aa). This variant belongs to Pango lineage B.1.1291, which also contains the D614G mutation in the Spike (S) gene. The B.1.1291 lineage is predominantly circulated in the United States of America (97.18%), although it was also found in other counties (Russia, Canada, Latvia, Chile, India, Japan, Colombia, Germany, Greece, Mexico, and UK). A total of 340 closely related variants to this novel variant were identified in GISAID database with collection dates ranged from 3/6/2020 to 10/21/2020. In addition, a search within NCBI Genbank database found that 108,405 of 873,230 (12.4%) SAR-CoV-2 complete genomes contain this truncated ORF8 protein mutation, indicating this mutation may arise spontaneously in other lineages as well. The wide distribution of this mutation indicates that this truncated ORF8 protein mutation may provide the virus a growth advantage and adaptive evolution.

Identification of a Novel SARS-CoV-2 Strain with Truncated Protein in ORF8 Gene by Next Generation Sequencing.

Using next generation sequencing technology, we identified a truncated protein mutation located in the ORF8 gene which is near the end of the genome from nucleotides 27,878 to 27,958. The mutation in this novel strain created a stop codon and translates to the novel truncated ORF8 protein, creating a much smaller protein than most other strains of SARS-CoV-2. The novel truncated mutation is most closely related to nine SARS-CoV-2 strains found in Washington state. Our results show a novel strain of SARS-CoV-2 with a truncated ORF8 gene. This shortens the translated ORF8 protein. The effects of ORF8 protein and its functions are still uncertain but a truncated ORF8 could affect antibody response, severity of infection and inflammatory response.