Transmission dynamics of SARS-CoV-2 within-host diversity in two major hospital outbreaks in South Africa
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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.
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SciScore for 10.1101/2020.11.15.20231993: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources We used LoFreq v. LoFreqsuggested: (LoFreq, RRID:SCR_013054)2.1.5 (Wilm et al., 2012) to call variants from the mpileup files generated using samtools software (version 1.8) (Li et al., 2009). samtoolssuggested: (SAMTOOLS, RRID:SCR_002105)Variants were then annotated using snpEff v. 4.5 (Cingolani et al., 2012b) and variation effects filtered using SnpSift v. snpEffsuggested: (SnpEff, RRID:SCR_005191)SnpSiftsuggested: (SnpSift, RRID:SCR_015624)Results from OddPub: Thank you for …
SciScore for 10.1101/2020.11.15.20231993: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources We used LoFreq v. LoFreqsuggested: (LoFreq, RRID:SCR_013054)2.1.5 (Wilm et al., 2012) to call variants from the mpileup files generated using samtools software (version 1.8) (Li et al., 2009). samtoolssuggested: (SAMTOOLS, RRID:SCR_002105)Variants were then annotated using snpEff v. 4.5 (Cingolani et al., 2012b) and variation effects filtered using SnpSift v. snpEffsuggested: (SnpEff, RRID:SCR_005191)SnpSiftsuggested: (SnpSift, RRID:SCR_015624)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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