Comparative analysis of within-host diversity among vaccinated COVID-19 patients infected with different SARS-CoV-2 variants

Abstract

SARS-CoV-2 is a rapidly evolving RNA virus that mutates within hosts and exists as viral quasispecies. Here, we evaluated the within-host diversity among vaccinated and unvaccinated individuals (n=379) infected with different SARS-CoV-2 variants of concern. The majority of samples harbored less than 14 iSNVs. Deep analysis revealed a significantly higher intra-host diversity in Omicron samples compared to other variants (p-value < 0.05). Vaccination status and type had a limited impact on intra-host diversity except for Beta-B.1.315 and Delta-B.1.617.2 vaccinees, who exhibited higher diversity compared to unvaccinated individuals (p-values: < 0.0001 and < 0.0021; respectively). Three immune-escape mutations were identified: S255F in Delta; and R346K and T376A in Omicron-B.1.1.529. The latter two mutations were fixed in BA.1 and BA.2 genomes, respectively. Overall, the relatively higher intra-host diversity among vaccinated individuals, and the detection of immune-escape mutations, despite rare, suggest a potential vaccine-induced immune pressure in vaccinated individuals.