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

Bioinformatics analysis of NGS data allows the generation of the consensus sequence of a viral genome from the of majority nucleotides at each position but also the identification of non-consensus nucleotides, enabling the exploration of intra-host variability but also its consequences on intra-host viral evolution [28] - [30] . All samples analysed in this study were probably infected by the same viral strain since they shared the same set of consensus SNVs. However, apart from 3 intra-host SNVs that were common between SRR10903401 and SRR10903402, there was no other overlap observed between the low frequency variants of each sample (Figure 1-B) . This indicates that these variations have been occurred in a rather random fashion and are not subject of selective pressures, which is also supported by the fact that the missense mutations were systematically more, compared to the synonymous mutations. On the other hand, missense substitutions are more common in loci involving pathogen resistance, indicating positive selection [31] . The analysed viral RNA might have been originated from functional/packed virions, but also from unpacked viral genomes, which are unable to replicate and infect other host cells. Even if a viral genome is unable to replicate independently, its abundant presence in the pool of viral quasispecies implies some functionality regarding the intra-host evolution and adaptation. For example, defective viral genomes might affect infection dynamics such as viral persistence but also the natural history of an infection [32] - [34] . At the same time, these variants may arise rapidly during an outbreak and can be used for tracking the transmission chains and the spaciotemporal characteristics author/funder. All rights reserved. No reuse allowed without permission.