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

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 sublineages (B.1.177 and sublineages 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 ∼5% 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.