Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2022

Patterns of within-host variation of SARS-CoV-2 (82387)

Jessica E Agius 1 2 3 , Jessica C Johnson-Mackinnon 1 2 3 , Winkie Fong 2 3 , Mailie Gall 2 4 , Connie Lam 3 , Kerri Basile 4 , Jen Kok 3 4 , Alicia Arnott 2 3 4 , Vitali Sintchenko 1 2 3 4 , Rebecca Rockett 1 2 3
  1. Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
  2. Westmead Institute for Medical Research, Sydney Institute for Infectious Diseases, Westmead, NSW, Australia
  3. Institute for Clinical Pathology and Medical Research , Centre for Infectious Diseases and Microbiology Public Health, Westmead, NSW, Australia
  4. Institute for Clinical Pathology and Medical Research, Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead, NSW, Australia

During the COVID-19 pandemic, the unprecedented scale of SARS-CoV-2 genomic surveillance has facilitated real-time monitoring of the virus, effectively tracking its spread and identifying new and emerging variants. Predominantly research on SARS-CoV-2 has focused on mutations observed in the consensus genome which represent the dominant variants. However, this study delves beneath the consensus to analyse within-host variants (iSNVs), which represent genetic variation within viral populations. Knowledge of within-host viral diversity can provide early indications of diagnostic dropouts, identify transmission events, and inform public health surveillance. Our research quantifies iSNV dynamics over the course of mild and severe SARS-CoV-2 infection in clinical cases and longitudinally within in vitro culture systems.

SARS-CoV-2 genomic diversity were examined in respiratory specimens cultured in Vero C1008 cells, and in two clinical cohorts (mild and severe disease) representing SARS-CoV-2 cases diagnosed in NSW, Australia between March 2020 and August 2021. Genomes were captured using the Respiratory Viral Oligo Panel and sequenced.

Within-host variants were detected in 83% (19/23) of the mild, and 100% of the severe (16/16) and culture (3/3) specimens. Patterns and frequencies of iSNVs were dynamic in clinical patients, with increases observed longitudinally. In culture, iSNVs were relatively consistent across sampling days and dilutions. Within-host variants detected in some SARS-CoV-2 lineages were shared within genomic clusters, highlighting transmission events between household members.

The findings from this study demonstrate the heterogeneity and dynamic frequency of iSNVs. Therefore, monitoring of sub-consensus mutations is critical to the ongoing effectiveness of immunisation, therapeutics, and containment measures during the pandemic.