Intra-host evolution during SARS-CoV-2 persistent infection

Abstract

Prolonged infection of SARS-CoV-2 represents a challenge to the development of effective public health policies to control the COVID-19 pandemic. The reason why some people have persistent infection and how the virus survives for so long are still not fully understood. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during persistent infection. Thirty-three patients who remained RT-PCR positive in the nasopharynx for at least 16 days were included in this study. Complete SARS-CoV-2 sequences were obtained for each patient at two time points. Phylogenetic, populational, and computational analysis of viral sequences confirmed persistent infection with evidence for a transmission cluster in health care professionals that shared the same workplace. A high number of missense variants targeting crucial structural and non-structural proteins such as Spike and Helicase was found. Interestingly, longitudinal acquisition of substitutions in Spike protein mapped many SARS-CoV-2 predicted T cell epitopes. Furthermore, the mutational profiles observed were suggestive of RNA editing enzyme activities, indicating innate immune mechanisms of the host cell. Viral quasispecies analysis corroborates persistent infection mainly by increasing richness and nucleotide diversity over time. Altogether, our findings highlight a dynamic and complex landscape of host and pathogen interaction during persistent infection suggesting that the host’s innate immunity shapes the increase of intra-host diversity with possible implications for therapeutic strategies and public health decisions during the COVID-19 pandemic.

Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil

“…Many mutations arise frequently in the SARS-CoV-2 genome during the virus replication cycle and intra-host defense mechanisms (22). However, most of these variants are lost as a result of the natural selection process, which also lead to fixation of some variants in the population.…”

Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil

“…Sequencing libraries were constructed using the Nextera DNA Flex Library Prep kit (Illumina, USA) and sequenced with the MiSeq Reagent Kit v3 (Illumina, USA). Next-generation sequencing (NGS) data was processed using a bioinformatic pipeline described in our previous study ( Voloch et al, 2020a ). Briefly, FastQC (v0.11.4) and trimmomatic v0.39 ( Bolger et al, 2014 ) was used for quality control analysis and bad quality reads filtration, respectively.…”

Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia

“…The authors highlight that the analysis of viral sequences confirmed persistent infection with evidence for a transmission cluster in health care professionals that shared the same workplace. In this case, the host’s innate immunity shapes the increase in intra-host diversity [ 22 ]. In our case, and in light of recent evidence, future studies are needed to fully prove this is a case of intra-host mutation.…”