A 21L/BA.2-21K/BA.1 “MixOmicron” SARS-CoV-2 hybrid undetected by qPCR that screen for variant in routine diagnosis

Abstract

Among the multiple SARS-CoV-2 variants identified since summer 2020, several have co-circulated, creating opportunities for coinfections and potentially genetic recombinations that are common in coronaviruses. Viral recombinants are indeed beginning to be reported more frequently. Here, we describe a new SARS-CoV-2 recombinant genome that is mostly that of a Omicron 21L/BA.2 variant but with a 3-prime tip originating from a Omicron 21K/BA.1 variant. Two such genomes were obtained in our institute from adults sampled in February 2022 in university hospitals of Marseille, southern France, by next-generation sequencing carried out with the Illumina or Nanopore technologies. The recombination site was located between nucleotides 26,858-27,382. In the two genomic assemblies, mean sequencing depth at mutation-harboring positions was 271 and 1,362 reads and mean prevalence of the majoritary nucleotide was 99.3+/-2.2% and 98.8+/-1.6%, respectively. Phylogeny generated trees with slightly different topologies according to whether genomes were depleted or not of the 3-prime tip. This 3-prime terminal end brought in the Omicron 21L/BA.2 genome a short transposable element of 41 nucleotides named S2m that is present in most SARS-CoV-2 except a few variants among which the Omicron 21L/BA.2 variant and may be involved in virulence. Importantly, this recombinant is not detected by currently used qPCR that screen for variants in routine diagnosis. The present observation emphasizes the need to survey closely the genetic pathways of SARS-CoV-2 variability by whole genome sequencing, and it could contribute to gain a better understanding of factors that lead to observed differences between epidemic potentials of the different variants.

A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab

“…Recently, an additional variant has been identified, generated from the recombination of the BA.1 and BA.2 subvariants, which has been found in patients co-infected with the two variants. However, the recombination site does not involve the epitope recognized by D3, suggesting that the mAb efficacy should not be compromised by this new emerging viral strain [ 26 , 27 ].…”

Recombination in Coronaviruses, with a Focus on SARS-CoV-2

“…Colson et al in Marseille detected two samples with a recombinant genome that was mostly that of a BA.2 variant but with a 3 tip originating from BA.1 [88]. Gu et al in Japan reported two more cases with a breakpoint near the 5 end of the Spike gene (nucleotide position 20,055-21,618) [89].…”

The Omicron variant of concern: Diversification and convergent evolution in spike protein, and escape from anti-Spike monoclonal antibodies

“…As expected for coronaviruses, multiple recombinants ( Focosi and Maggi, 2022 ) have been detected to date (designed by the PANGOLIN nomenclature with the “X” prefix and progressive alphabet letters, with one more letter added when the alphabet is over), with the left part of the description indicating the Spike donor lineage. The recombinants can be summarized as follows: DeltaxBA.1: XD (France and Denmark ( Zayet et al, 2022 )), XF (UK) DeltaxBA.1.1: XS (USA) BA.1xBA.2 ( Colson et al, 2022 ): XE (a.k.a. V-22APR-02 in PHE), XG (Denmark), XH (Denmark), XJ (Finland), XK (Belgium), XN (UK), XT (South Africa), XU (India), XV (Denmark and Italy), XW (USA, Germany, England), XY (USA), XAA (USA), XAB (Germany), XAC (Canada and USA), XAF (Costa Rica), XAG (Brazil), XAK (Germany), XAL (Germany), XAQ (Canada), XAR (Reunion) BA.1.1xBA.2: XM (Europe), XP (UK), XQ (UK), XR (UK), and XZ BA.1.1xBA.2.9: XAM (Panama and USA), XAU (Spain, England, France) BA.2xBA.1: XAD (Germany), XAE (USA, Chile), XAH (Slovenia), XAP (USA) BA.2.3.13xBA.1: XAT (Japan) BA.2xBA.4: BA.2.12.1xBA.4 (England) BA.2xBA.5: XAV (USA, Scotland) BA.2xBA.5.1: XAN (Spain, Denmark) BA.2.5xBA.5: XAZ (France, Germany, Croatia, Denmark and USA) BA.2.76xBA.5.2: (PANGO issue #896) BA.2xDelta: BA.2xAY.122x: XAW (Russia) BA.2xAY.45: XAY/C1 (South Africa) C2 BA.5xBA.2: XAS (USA) BA.2.75xBJ.1: XBB …”

“…BA.1xBA.2 ( Colson et al, 2022 ): XE (a.k.a. V-22APR-02 in PHE), XG (Denmark), XH (Denmark), XJ (Finland), XK (Belgium), XN (UK), XT (South Africa), XU (India), XV (Denmark and Italy), XW (USA, Germany, England), XY (USA), XAA (USA), XAB (Germany), XAC (Canada and USA), XAF (Costa Rica), XAG (Brazil), XAK (Germany), XAL (Germany), XAQ (Canada), XAR (Reunion) BA.1.1xBA.2: XM (Europe), XP (UK), XQ (UK), XR (UK), and XZ BA.1.1xBA.2.9: XAM (Panama and USA), XAU (Spain, England, France) …”