Genetic features of SARS-Cov2 Omicron in Apulia Region

In late November 2021 a new SARS-CoV-2 variant with increased transmissibility emerged. The new variant B.1.1.529 was first discovered in a patient in Southern Africa (PMID:35042229) and then it spread worldwide becoming today the most represented one. Consequently, the World Health Organization (WHO) classified this variant as Variant of Concern (VoC) and named it Omicron. Our Institute is actively involved in the SARSCoV-2 genomic surveillance, therefore we have been able to monitor the spread of the variant throughout the Apulia Region, in South East of Italy, which by late December 2021 appeared to be the predominant one. Currently, more than 590 Omicron SARS-CoV-2 genomes have been sequenced in Apulia and made available on the GISAID platform. Of these, 386 genomes have been sequenced by our laboratory following an established procedure (doi:10.3390/v13050731) and analyzed through the I-Co-Gen platform (https://irida.iss.it/irida21-aries). We conducted a genetic diversity analysis focusing on identified amino acid mutations, mainly in structural proteins. Particularly, the mutations in Spike protein are able to enhance infection and immune escape (PMID:35337047), that can explain the wide spread of the Omicron VoC. We identified in our dataset two of the three genetically distinct Omicron lineages: BA.1 (274/386 – 71%) and BA.2 (112/386- 29%), with several related sub-lineages. We performed a mutation analysis with respect to the SARS-CoV-2 reference genome (Entrez AC:NC_045512.2). As expected, the protein that accumulated the highest number of mutations was the Spike (S) protein. For all the strains sequenced we calculated the total number of non-synonymous mutations detected in genes encoded structural proteins. We identified a total of 73 unique aminoacid changes in the Spike protein; 22 in the Nucleocapside protein; 9 in the Membrane protein; 2 in the Envelope protein. Seven S-protein mutations, S:D614G, S:H655Y, S:N679K, S:P681H, S:N764K, S:D796Y, S:Q954H and S:N969K, were detected in all sequenced strains, and were typically described in the Omicron variant. In the other genes, the most frequently observed mutations were E:T9I, M:19E, M:A63T, N:P13L, N:R203K, N:G204R, S:A67V, S:S373P, S:S375F, S:K417N, S:N440K, S:S477N, S:T487K, S:E484A, S:Q493R, S:Q498R, S:N501Y and S:Y505H. We also identified the majority of mutations peculiar of each Omicron sublineage. Finally, we also detected previously unobserved mutations, e.g. N:S413R identified in strains belonging to lineage BA.2. This result suggests the existence of ongoing evolution occurring within the Omicron variant. Some mutations detected with high frequency were previously identified in other VoC (S:A67V in Alpha and Beta, S:P681H in Alpha, S:N679K in Gamma). Together with the other mutations described, these might be related to transmissibility and immune escape of the virus. Considering the lower clinical implications of the Omicron variant, we could hypothesize that such mutations are not correlated with disease severity. The continuing surveillance efforts, together with more transcriptomic and/or proteomic analyses of SARS-CoV-2 variants should be conducted to better explore the effect of mutations and understand the evolution of the virus.