Intra-host variability of SARS-CoV-2: Patterns, causes and impact on COVID-19

Intra-host viral variability is related to pathogenicity, persistence, drug resistance, and the emergence of new clades. This work reviews the large amount of data on SARS-CoV-2 intra-host variability accumulated to date, addressing known and potential implications in COVID-19 and the emergence of VOCs and lineage-defining mutations. Topics covered include the distribution of intra-host polymorphisms across the genome, the corresponding mutational signatures, their patterns of emergence and extinction throughout infection, and the processes governing their abundance, frequency, and type (synonymous, nonsynonymous, indels, nonsense). Besides, evidence is reviewed that the virus can replicate and mutate in isolation at different anatomical compartments, which may imply that what we have learned from respiratory samples could be part of a broader picture.