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

As it is well documented, recombination events lead to substantial changes in genetic diversity of RNA viruses [40] , [41] . In CoVs, discontinuous RNA synthesis is commonly observed, resulting in high frequencies of homologous recombination [42] , which can be up to 25% across the entire CoV genome [43] . For pathogenic HCoVs genomic rearrangements are frequently reported during the course of epidemic outbreaks, such as HCoV-OC43 [44] , and HCoV-NL63 [45] , SARS-CoV [46] [44] and MERS-CoV [47] . We have isolated intra-host genomic rearrangements, located in poly-A and poly-U enriched palindrome regions across the SARS-CoV-2 genome (Figure 3, Suppl. Figure 1) . We have validated the majority of these events by visual inspection of the alignments. We conclude that these rearrangements do not represent artifacts derived from the NGS library preparation (e.g. PCR crosstalk artifacts), especially since all the supporting reads were not duplicated and, in some cases, differed in polymorphic positions (Suppl. Figure 2) .