Two-step fitness selection for intra-host variations in SARS-CoV-2

Abstract

Spontaneous mutations introduce uncertainty into COVID-19 control procedures and vaccine development. Here, we perform spatio-temporal analysis on intra-host single-nucleotide variations (iSNVs) in 402 clinical samples from 170 patients, which reveals an increase in genetic diversity over time post-symptoms onset within individual patients. Nonsynonymous mutations are over-represented in the pool of iSNVs, but underrepresent at the single nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated within the host (positive selection), and these substitutions tend to be unfixed as SNPs in population (negative selection). Dynamic iSNVs changes in subpopulations of different gender, age, illness severity and viral shedding time displayed a varied fitness selection process among populations. Taken together, our study highlights iSNVs provide a mutational pool shaping the virus rapid global evolution.

SARS-CoV-2 evolution and evasion from multiple antibody treatments in a cancer patient

“…Consistent with previous studies, the immunocompromised viral genome had more intra-host mutations, greater enrichment of nonsynonymous mutations in the Spike protein and increased fixation of minor mutations when compared to samples taken from immunocompetent hosts 3 . Many of the emerging RBD mutations have been previously associated with escape from binding by monoclonal antibody treatment, implying that these mutations were partly responsible for the virus overcoming neutralization by antibodies and, through a process of strong positive selection, their emergence was a consequence of the antibody treatment 15 (Figure 3).…”

High Level of SARS-CoV-2 Infection in Young Population Is a Predictor for Peak Incidence

“…Such mutation-prone expansion of zoonotic RNA virus provides the molecular basis for the acquisition of fitness to adapt to the human host. Based on our findings and studies by other groups, we further hypothesized that the directional selection of SARS-CoV-2 increases fitness to young age group with decreased fatality ( Li et al, 2022 ; Shuai et al, 2022 ). In our results, fatality of SARS-CoV-2 decreased in Delta peak compared to previous three peaks with the main SARS-CoV-2-infected age group shifting to a younger group.…”

“…Delta variants were less pathogenic compared to previous isolates including Alpha and Beta variants in a mouse model ( Shuai et al, 2022 ). In addition, more frequent intra-host single-nucleotide SARS-CoV-2 variant accumulation was observed in young patients compared to old patients, suggesting higher chance for genetic adaptation in younger hosts ( Li et al, 2022 ). Overall, these studies support our hypothesis about SARS-CoV-2 evolution despite the high social contact among young people and prior vaccination of old aged group still significantly contribute higher level of SARS-CoV-2 infection in younger age groups.…”

Analysis of SARS-CoV-2 in Nasopharyngeal Samples from Patients with COVID-19 Illustrates Population Variation and Diverse Phenotypes, Placing the Growth Properties of Variants of Concern in Context with Other Lineages

“…However, most nucleotide changes reverted 3 days later in cell culture. This suggests minimal intrahost variation at least early during infection, although increased variation has been observed over longer periods ( 34 , 35 ).…”