Drivers of within-host genetic diversity in acute infections of viruses

Gelbart, Maoz; Harari, Sheri; Ben-Ari, Ya'ara; Kustin, Talia; Wolf, Dana; Mandelboim, Michal; Mor, Orna; Pennings, Pleuni S.; Stern, Adi

doi:10.1371/journal.ppat.1009029

Cited by 26 publications

(33 citation statements)

References 51 publications

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“…Bioinformatic analysis and lineage assignment. Sequencing reads were trimmed using pTrimmer v1.3.1, a multiplexing primer trimming tool 33 , and then aligned to the reference genome of SARS-CoV-2 (GenBank ID MN908947) using our AccuNGS V1 pipeline 34 that is based on BLAST 35 , using a particular stringent e-value of 10 −30 . We then set out to determine the consensus sequence of each sample.…”

Section: Methodsmentioning

confidence: 99%

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Kustin

Harel

Finkel

et al. 2021

Nat Med

Self Cite

301

178

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The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.

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Section: Methodsmentioning

confidence: 99%

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Kustin

Harel

Finkel

et al. 2021

Nat Med

Self Cite

301

178

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“…Two samples had a particularly high number (15 and 18) of iSNVs, each with high and correlated MAFs consistent with coinfection by two diverse variant haplotypes ( 38 ). For one of these samples, laboratory contamination was unlikely because we could not identify any samples that could be the source.…”

Section: Within-host Variants Are Present In Most Sars-cov-2 Samplesmentioning

confidence: 99%

SARS-CoV-2 within-host diversity and transmission

Lythgoe

Hall

Ferretti

et al. 2021

Science

340

362

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Extensive global sampling and sequencing of the pandemic virus SARS-CoV-2 have enabled researchers to monitor its spread, and to identify concerning new variants. Two important determinants of variant spread are how frequently they arise within individuals, and how likely they are to be transmitted. To characterize within-host diversity and transmission we deep-sequenced 1313 clinical samples from the UK. SARS-CoV-2 infections are characterized by low levels of within-host diversity when viral loads are high, and a narrow bottleneck at transmission. Most variants are either lost, or occasionally fixed, at the point of transmission, with minimal persistence of shared diversity - patterns which are readily observable on the phylogenetic tree. Our results suggest that transmission-enhancing and/or immune-escape variants are likely to arise infrequently, but could spread rapidly if successfully transmitted.

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“…Sequencing reads were trimmed using pTrimmer, a multiplexing primer trimming tool [20], and then aligned to the reference genome of SARS-CoV-2 (GenBank ID MN908947) using our AccuNGS pipeline [21] that is based on BLAST [22], using a particular stringent e-value of 10 #$% . We then set out to determine the consensus sequence of each sample.…”

Section: Bioinformatic Analysis and Lineage Assignmentmentioning

confidence: 99%

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

Kustin

Harel

Finkel

et al. 2021

Preprint

Self Cite

109

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The SARS-CoV-2 pandemic has been raging for over a year, creating global detrimental impact. The BNT162b2 mRNA vaccine has demonstrated high protection levels, yet apprehension exists that several variants of concerns (VOCs) can surmount the immune defenses generated by the vaccines. Neutralization assays have revealed some reduction in neutralization of VOCs B.1.1.7 and B.1.351, but the relevance of these assays in real life remains unclear. Here, we performed a case-control study that examined whether BNT162b2 vaccinees with documented SARS-CoV-2 infection were more likely to become infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals. Vaccinees infected at least a week after the second dose were disproportionally infected with B.1.351 (odds ratio of 8:1). Those infected between two weeks after the first dose and one week after the second dose, were disproportionally infected by B.1.1.7 (odds ratio of 26:10), suggesting reduced vaccine effectiveness against both VOCs under different dosage/timing conditions. Nevertheless, the B.1.351 incidence in Israel to-date remains low and vaccine effectiveness remains high against B.1.1.7, among those fully vaccinated. These results overall suggest that vaccine breakthrough infection is more frequent with both VOCs, yet a combination of mass-vaccination with two doses coupled with non-pharmaceutical interventions control and contain their spread.

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Drivers of within-host genetic diversity in acute infections of viruses

Cited by 26 publications

References 51 publications

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

SARS-CoV-2 within-host diversity and transmission

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals

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