Characterization of SARS-CoV-2 viral diversity within and across hosts

Sashittal, Palash; Luo, Yu; Peng, Jian; El-Kebir, Mohammed

doi:10.1101/2020.05.07.083410

Cited by 24 publications

(26 citation statements)

References 57 publications

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“…The identification of iSNVs in fecal samples as well as in throat swab and bronchoalveolar lavage fluid, suggest ongoing evolution of SARS-CoV-2 in the human body ( Rose et al, 2020 ; Sashittal et al, 2020 ; Shen et al, 2020 ; Y. Wang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence

Kang

Shen

et al. 2020

Journal of Genetics and Genomics

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In response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission, and evolution of SARS-CoV-2, which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown. Eighteen time-series fecal samples were collected from nine COVID-19 patients during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method. First, we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Moreover, the evolving of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period. Meanwhile, we also found that the same mutation showed distinct pattern of frequency changes in different individuals, indicating a strong random drift. In summary, dramatic changes of SARS-CoV-2 genome were detected in fecal samples during the convalescent period; whether the viral load in feces is sufficient to establish an infection warranted further investigation.

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Section: Discussionmentioning

confidence: 99%

Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence

Kang

Shen

et al. 2020

Journal of Genetics and Genomics

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“…The identification of iSNVs in fecal samples as well as in throat swab and bronchoalveolar lavage fluid, suggest ongoing evolution of SARS-CoV-2 in the human body (19)(20)(21)(22). However, the possibility of infection of multiple strains cannot be entirely ruled out.…”

Section: Discussionmentioning

confidence: 99%

Hybrid capture-based sequencing enables unbiased recovery of SAR-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants

Kang

et al. 2020

Preprint

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Background: In response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission, and evolution of SARS-CoV-2, which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown, partly due to the difficulty of obtaining unbiased genome coverage of SARS-CoV-2 directly from clinical samples. Methods: Eighteen time series fecal samples were collected from nine COVID-19 patients during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method with different rounds of hybridization. Results: By examining the sequencing depth, genome coverage, and allele frequency change, we demonstrated the impeccable performance of the hybrid capture method in samples with Ct value < 34, as well as significant improvement comparing to direct metatranscriptomic sequencing in samples with lower viral loads. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Meanwhile, we also found that the same mutation showed different frequency changes in different individuals, indicating a strong random drift. Moreover, the evolving of the viral genome demonstrated that the virus was still viable in the gastrointestinal tract during the convalescent period. Conclusions: The hybrid capture method enables reliable analyses of inter- and intra-host variants of SARS-CoV-2 genome, which changed dramatically in the gastrointestinal tract; its clinical relevance warrants further investigation.

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“…example, artefactual biases in mutational processes could confound signatures of mutational hotspots [29][30][31][32][33][34]. The issue of whether or not recombination has occurred during the outbreak is critical to the immunological battles against the virus and is under intense debate [7,[35][36][37][38][39][40][41]. Because many tests of recombination assume that all mutations can only occur once at each site, recurrent mutation and systematic errors can confound signatures of recombination [7,27,36].…”

Section: Plos Geneticsmentioning

confidence: 99%

Stability of SARS-CoV-2 phylogenies

et al. 2020

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The SARS-CoV-2 pandemic has led to unprecedented, nearly real-time genetic tracing due to the rapid community sequencing response. Researchers immediately leveraged these data to infer the evolutionary relationships among viral samples and to study key biological questions, including whether host viral genome editing and recombination are features of SARS-CoV-2 evolution. This global sequencing effort is inherently decentralized and must rely on data collected by many labs using a wide variety of molecular and bioinformatic techniques. There is thus a strong possibility that systematic errors associated with lab—or protocol—specific practices affect some sequences in the repositories. We find that some recurrent mutations in reported SARS-CoV-2 genome sequences have been observed predominantly or exclusively by single labs, co-localize with commonly used primer binding sites and are more likely to affect the protein-coding sequences than other similarly recurrent mutations. We show that their inclusion can affect phylogenetic inference on scales relevant to local lineage tracing, and make it appear as though there has been an excess of recurrent mutation or recombination among viral lineages. We suggest how samples can be screened and problematic variants removed, and we plan to regularly inform the scientific community with our updated results as more SARS-CoV-2 genome sequences are shared (https://virological.org/t/issues-with-sars-cov-2-sequencing-data/473 and https://virological.org/t/masking-strategies-for-sars-cov-2-alignments/480). We also develop tools for comparing and visualizing differences among very large phylogenies and we show that consistent clade- and tree-based comparisons can be made between phylogenies produced by different groups. These will facilitate evolutionary inferences and comparisons among phylogenies produced for a wide array of purposes. Building on the SARS-CoV-2 Genome Browser at UCSC, we present a toolkit to compare, analyze and combine SARS-CoV-2 phylogenies, find and remove potential sequencing errors and establish a widely shared, stable clade structure for a more accurate scientific inference and discourse.

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Characterization of SARS-CoV-2 viral diversity within and across hosts

Cited by 24 publications

References 57 publications

Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence

Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence

Hybrid capture-based sequencing enables unbiased recovery of SAR-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants

Stability of SARS-CoV-2 phylogenies

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