First Detection of the SARS-CoV-2 Omicron BA.5/22B in Monaco

The Omicron BA.5/22B variant has been designated as a "variant of concern" by the World Health Organization. We describe, here, the first evidence in Monaco of infection with an Omicron BA.5/22B variant, probably imported from the Republic of Seychelles, harboring a rare combination of non-BA.5/22B signature amino acid changes. SARS-CoV-2 neutralizing antibodies were measured with a surrogate virus neutralization test. SARS-CoV-2 genotype screening was performed on nasopharyngeal samples with a multiplex qPCR assay. The SARS-CoV-2 genome was obtained by next-generation sequencing with the Illumina COVID-seq protocol, then assembly using bioinformatics pipelines and software was performed. The BA.5/22B spike protein structure was obtained by molecular modeling. Two spouses were SARS-CoV-2-diagnosed the day they returned from a one-week trip in the Republic of Seychelles. SARS-CoV-2 qPCR screening for variant-specific mutations identified an Omicron variant BA.1/21K, BA.4/22A, or BA.5/22B. A SARS-Co-2 BA.5/22B variant genome was recovered from one of the spouses. Aside from BA.5/22B-defining amino acid substitutions, four other amino acid changes were encoded including Q556K in ORF1a, K2557R in ORF1b, and A67V and A829T in spike; only 13 genomes in sequence databases harbored these four mutations concurrently. Structural analysis of this BA.5/22B variant predicted that A829T in spike may result in a compaction that may affect conformational plasticity. Overall, our findings warrant performing genome-based genotypic surveillance to survey accurately the emergence and circulation of SARS-CoV-2 variants worldwide and point out that their first occurrence in a country is often through international travel despite implemented countermeasures.