CHARACTERIZING WITHIN-HOST DIVERSITY IN SHORT-TERM AND VACCINATED COVID-19 PATIENTS

Abstract

SARS-CoV-2 is the etiological agent of the ongoing COVID-19 pandemic, which has caused massive losses in human lives and strained global health resources. The ongoing vaccination campaigns in many countries have spurred hope that the pandemic's end is in sight. However, the emergence of variants, namely Alpha, Beta, Delta and Omicron, have raised concerns about the effectiveness of these vaccines and other antibody-based therapies. Consequently, the challenge to control the COVID-19 pandemic is beyond deepened as some of SARS-CoV-2 variants, including the recent Omicron variants, have an expanded transmissibility and resistance. The evolution of coronaviruses, like other RNA viruses, begins with the accumulation of mutations within hosts, a few of which may rise in frequency and transmit to other hosts. Here, we aimed to characterize the within-host mutations of SARS-CoV-2 in short-term Delta-infected patients and unvaccinated Omicron-infected individuals. A total of 22 patients of short-term Delta positive (three time points) samples and a total of 421 unvaccinated and vaccinated Omicron-positive samples were sequenced. The within-host diversity was significantly higher among vaccinated individuals in BA.5.2.1 Omicron sub-lineage. Moreover, non-lineage aa mutations were observed in each lineage and sub-lineages, thus accumulation of those mutations in the viral genome among vaccinated population could be lineage or sub-lineage specific. Additionally, a total of fifteen pathogenic non-lineage specific amino acid mutations in S-gene were observed with more than 30% prevalence among vaccinated individuals. In conclusion, it is worthy to further investigate the non-lineage specific mutations, specifically with prevalence of more than 40% and pathogenic mutations, for immune escape analysis.