The first three waves of the Covid-19 pandemic hint at a limited genetic repertoire for SARS-CoV-2

Abstract

The genomic diversity of SARS-CoV-2 is the result of a relatively low level of spontaneous mutations introduced during viral replication. With millions of SARS-CoV-2 genome sequences now available, we can begin to assess the overall genetic repertoire of this virus. We find that during 2020 there was a global wave of one variant that went largely unnoticed, possibly because its members were divided over several sub-lineages (B.1.177 and sub-lineages B.1.177.XX). We collectively call this Janus, and it was eventually replaced by the Alpha (B.1.1.7) Variant of Concern (VoC), next replaced by Delta (B.1.617.2), which itself might soon be replaced by a fourth pandemic wave consisting of Omicron (B.1.1.529). We observe that splitting up and redefining variant lineages over time, as was the case with Janus and is now happening with Alpha, Delta, and Omicron, is not helpful to describe the epidemic waves spreading globally. Only about five percent of the 30,000 nucleotides of the SARS-CoV-2 genome are found to be variable. We conclude that a fourth wave of the pandemic with the Omicron variant might not be that different from other VoCs, and that we may already have the tools in hand to effectively deal with this new VoC.

In-depth genetic characterization of the SARS-CoV-2 pandemic in a two-year frame in North Macedonia using second and third generation sequencing technologies

“…human bronchial and nasal airway epithelial cultures (42). As of early December 2021, this mutation is found in >99% of the 6 million viral genomes in the GISAID database (43). The RBD N501Y mutation increases the binding affinity to the ACE-2 receptor and transmissibility (6,44) and in our study it reached a frequency of 60.98%.…”

“…Given that it emerged relatively late in the pandemic, in June 2020, the mutation N:D63G is very intriguing. The nucleoprotein N, which is the most abundant protein and is responsible for packaging the viral genome, is most likely to have had an impact on infectious virus titers (43). The most striking and statistically significant difference was observed among the haplotype 2C_1 cases, where 10.5% of the patients were hospitalized due to severe clinical condition (p=0.0013).…”

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk and enhanced NTD dynamics

“…Liu et al, 2022). Notably, the D614G mutation has been conserved across all major variants of concern (Wassenaar et al, 2022). Additionally, the P681R mutation found in the Delta S and Omicron BA.1 S has been found to increase pathogenicity and proteolytic processing (Y.…”

“…However, the emergence of numerous variants of concern have created an additional challenge to treatment and prevention efforts. The periodic emergence of new variants of concern beginning with Alpha, and later including Delta and most recently Omicron BA.1, have contributed to surges in cases worldwide (Wassenaar et al, 2022). SARS-CoV-2 is a member of the family Coronavirdae along with other human pathogens including SARS-CoV and MERS (Corman et al, 2018).…”

SARS-CoV-2 variants show temperature-dependent enhanced polymerase activity in the upper respiratory tract and high transmissibility

“…In this study, we demonstrate that the P323L or P323L/G671S mutation in the NSP12 results in enhanced transmissibility due to the increased viral growth properties and extended infectious virus shedding duration in the upper respiratory tract. Interestingly, all Omicron variants, from BA.1 to BA.5, commonly harbor the NSP12 P323L mutation [29][30][31] and BA.2.75 Omicron variants also carry the NSP12 P323L/G671S mutation 32 , similar to the Delta variant. These NSP12 mutations may be responsible for high transmissibility of Omicron variants.…”