SARS-CoV-2 exhibits intra-host genomic plasticity and low-frequency polymorphic quasispecies

Timokratis Karamitros; Gethsimani Papadopoulou; Maria Bousali; Anastasios Mexias; Sotiris Tsiodras; Andreas Mentis

The comparison of all SNVs (intra-host and population level) with the genomic targets of the molecular diagnostics assays, revealed colocalizations of three intra-host SNVs and 2 isolate-specific SNVs with primers and probes currently in use. In detail, intra-host SNVs colocalized with the probe of RdRP_SARSr reaction (15, The de novo assembly of the viral genomes revealed intra-host genomic rearrangements. For samples SRR10903401 and SRR10903402, these large-scale structural events were systematically observed over poly-A / poly-U-rich genomic regions, located in ORF1ab and S genes. In all cases, similar or identical strings of nucleotides in close proximity appear to have served as seeds for homologous recombination events. All rearrangements were validated by remapping of the raw reads on the corresponding de novo assembled contigs, setting a threshold of at least 5 supporting reads of high mapping quality (>40) in each case. For sample SRR10903401 we isolated three inversions/misassemblies in ORF1ab (Suppl. Figure 2 ) and one inversion/misassembly in S gene (Figure 3-A) . Notably, we were able to validate the same inversion in S gene for sample SRR10903402 as well (Figure 3-B) .