tetano
Editor, Senior Moderator
Virus Evol
. 2021 Apr 21;7(1):veab041.
doi: 10.1093/ve/veab041. eCollection 2021 Jan.
Transmission dynamics of SARS-CoV-2 within-host diversity in two major hospital outbreaks in South Africa
James E San[SUP] 1 [/SUP], Sinaye Ngcapu[SUP] 2 3 [/SUP], Aquillah M Kanzi[SUP] 1 [/SUP], Houriiyah Tegally[SUP] 1 [/SUP], Vagner Fonseca[SUP] 1 [/SUP], Jennifer Giandhari[SUP] 1 [/SUP], Eduan Wilkinson[SUP] 1 [/SUP], Chase W Nelson[SUP] 4 5 [/SUP], Werner Smidt[SUP] 1 6 [/SUP], Anmol M Kiran[SUP] 7 8 [/SUP], Benjamin Chimukangara[SUP] 1 [/SUP], Sureshnee Pillay[SUP] 1 [/SUP], Lavanya Singh[SUP] 1 [/SUP], Maryam Fish[SUP] 1 [/SUP], Inbal Gazy[SUP] 1 [/SUP], Darren P Martin[SUP] 9 [/SUP], Khulekani Khanyile[SUP] 1 [/SUP], Richard Lessells[SUP] 1 [/SUP], Tulio de Oliveira[SUP] 1 10 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute, highly transmissible respiratory infection in humans and a wide range of animal species. Its rapid global spread has resulted in a major public health emergency, necessitating commensurately rapid research to improve control strategies. In particular, the ability to effectively retrace transmission chains in outbreaks remains a major challenge, partly due to our limited understanding of the virus' underlying evolutionary dynamics within and between hosts. We used high-throughput sequencing whole-genome data coupled with bottleneck analysis to retrace the pathways of viral transmission in two nosocomial outbreaks that were previously characterised by epidemiological and phylogenetic methods. Additionally, we assessed the mutational landscape, selection pressures, and diversity at the within-host level for both outbreaks. Our findings show evidence of within-host selection and transmission of variants between samples. Both bottleneck and diversity analyses highlight within-host and consensus-level variants shared by putative source-recipient pairs in both outbreaks, suggesting that certain within-host variants in these outbreaks may have been transmitted upon infection rather than arising de novo independently within multiple hosts. Overall, our findings demonstrate the utility of combining within-host diversity and bottleneck estimations for elucidating transmission events in SARS-CoV-2 outbreaks, provide insight into the maintenance of viral genetic diversity, provide a list of candidate targets of positive selection for further investigation, and demonstrate that within-host variants can be transferred between patients. Together these results will help in developing strategies to understand the nature of transmission events and curtail the spread of SARS-CoV-2.
Keywords: NGS whole-genome sequencing; SARS-CoV-2; South Africa; bottleneck; nonsynonymous; selection; transmission dynamics; within-host variants.
. 2021 Apr 21;7(1):veab041.
doi: 10.1093/ve/veab041. eCollection 2021 Jan.
Transmission dynamics of SARS-CoV-2 within-host diversity in two major hospital outbreaks in South Africa
James E San[SUP] 1 [/SUP], Sinaye Ngcapu[SUP] 2 3 [/SUP], Aquillah M Kanzi[SUP] 1 [/SUP], Houriiyah Tegally[SUP] 1 [/SUP], Vagner Fonseca[SUP] 1 [/SUP], Jennifer Giandhari[SUP] 1 [/SUP], Eduan Wilkinson[SUP] 1 [/SUP], Chase W Nelson[SUP] 4 5 [/SUP], Werner Smidt[SUP] 1 6 [/SUP], Anmol M Kiran[SUP] 7 8 [/SUP], Benjamin Chimukangara[SUP] 1 [/SUP], Sureshnee Pillay[SUP] 1 [/SUP], Lavanya Singh[SUP] 1 [/SUP], Maryam Fish[SUP] 1 [/SUP], Inbal Gazy[SUP] 1 [/SUP], Darren P Martin[SUP] 9 [/SUP], Khulekani Khanyile[SUP] 1 [/SUP], Richard Lessells[SUP] 1 [/SUP], Tulio de Oliveira[SUP] 1 10 [/SUP]
Affiliations
- PMID: 34035952
- PMCID: PMC8135343
- DOI: 10.1093/ve/veab041
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute, highly transmissible respiratory infection in humans and a wide range of animal species. Its rapid global spread has resulted in a major public health emergency, necessitating commensurately rapid research to improve control strategies. In particular, the ability to effectively retrace transmission chains in outbreaks remains a major challenge, partly due to our limited understanding of the virus' underlying evolutionary dynamics within and between hosts. We used high-throughput sequencing whole-genome data coupled with bottleneck analysis to retrace the pathways of viral transmission in two nosocomial outbreaks that were previously characterised by epidemiological and phylogenetic methods. Additionally, we assessed the mutational landscape, selection pressures, and diversity at the within-host level for both outbreaks. Our findings show evidence of within-host selection and transmission of variants between samples. Both bottleneck and diversity analyses highlight within-host and consensus-level variants shared by putative source-recipient pairs in both outbreaks, suggesting that certain within-host variants in these outbreaks may have been transmitted upon infection rather than arising de novo independently within multiple hosts. Overall, our findings demonstrate the utility of combining within-host diversity and bottleneck estimations for elucidating transmission events in SARS-CoV-2 outbreaks, provide insight into the maintenance of viral genetic diversity, provide a list of candidate targets of positive selection for further investigation, and demonstrate that within-host variants can be transferred between patients. Together these results will help in developing strategies to understand the nature of transmission events and curtail the spread of SARS-CoV-2.
Keywords: NGS whole-genome sequencing; SARS-CoV-2; South Africa; bottleneck; nonsynonymous; selection; transmission dynamics; within-host variants.