The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is currently driven by the highly infectious Omicron variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which was first detected in Botswana on November 11, 2021 and subsequently spread as the dominant variant (https://covid19. who. int/). Since then, Omicron has evolved into distinct sub-lineages and descendant lineages [1], characterised by different mutations in the spike (S) protein compared to the wild type (WT) ancestral strain, and further mutations involving the other open reading frames (ORFs). This not only strengthened binding to the angiotensin converting enzyme 2 (ACE2) receptor [2], resulting in increased infectivity/transmissibility of these variants [3], but also compromised the protection provided by vaccines or humoral immunity induced by previous infections [4–6]. The SARS-CoV-2 genome encodes for 16 non-structural proteins in addition to the replicase polyprotein, the S glycoprotein, envelope (E), membrane (M), nucleocapsid (N) and other accessory proteins [7]. Some single nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome have already been identified and described in previous variants. For example, it has been reported that the D614G mutation (aspartate to glycine) in the S gene results in increased transduction in human epithelial cells [8] or the R203K and G204R mutations in the N gene increase viral fitness [9].

In the last few weeks, the new sub variant XBB. 1.5 has emerged, causing concern globally. It currently accounts for about 75% of COVID-19 cases in the US, according to projections by the US Centres for Disease Control and Prevention (CDC, https://www. cdc. gov/coronavirus/2 0 19-ncov/covid-data/covidview/index. html). XBB. 1.5 is a sub-lineage of XBB with an additional mutation mapped to the spike protein (S486P)(https://www. ecdc. europa. eu/en/new s-events/update-sars-cov-2-variants-ecdc-assessment-xbb15-sub-lineag e). This mutation has been rare during the pandemic, probably because it requires two nucleotide substitutions in the same codon to change the amino acid sequence: from serine to proline. A recent investigation demonstrated that XBB. 1.5 is not associated with a higher reduction in neutralisation by vaccine and convalescent sera compared to XBB. 1, but that it is associated with a higher ACE2