SARS-CoV-2 within-host diversity and transmission

Lythgoe, Katrina A.; Hall, Matthew; Ferretti, Luca; Cesare, Mariateresa de; MacIntyre-Cockett, George; Trebes, Amy; Andersson, Monique; Otecko, Newton O.; Wise, Emma L.; Moore, Nathan; Lynch, Jessica; Kidd, Stephen P.; Cortes, Nicholas; Mori, Matilde; Williams, Rebecca; Vernet, Gabrielle; Justice, Anita; Green, Angie; Nicholls, Samuel M.; Ansari, Azim; Abeler-Dörner, Lucie; Moore, Catrin E.; Peto, Timothy E. A.; Eyre, David W; Shaw, R. H.; Simmonds, Peter; Buck, David; Todd, John A.; Connor, Thomas R.; Ashraf, Shirin; Filipe, Ana da Silva; Shepherd, James G.; Thomson, Emma C.; Bonsall, David; Fraser, Christophe; Golubchik, Tanya

doi:10.1126/science.abg0821

Cited by 356 publications

(458 citation statements)

References 76 publications

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“…Consistent with this bottleneck, sequencing studies have provided conflicting results with respect to the ability of intrahost variants to transmit and establish new SARS-CoV-2 lineages that have the potential to transmit widely. While a number of studies have shown this to be the case 16,17,20,21 , other studies have not been able to demonstrate transmission of viral lineages derived from intrahost evolution 11,22,23 . The stochasticity in inter-host transmission of specific viral lineages is compounded by the overdispersed nature of SARS-CoV-2 spread, where most onward transmission originates from a small number of individuals.…”

Section: Introductionmentioning

confidence: 99%

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Controlling long-term SARS-CoV-2 infections is important for slowing viral evolution

Egeren

Novokhodko

Stoddard³

et al. 2021

Preprint

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The rapid emergence and expansion of novel SARS-CoV-2 variants is an unpleasant surprise that threatens our ability to achieve herd immunity for COVID-19. These fitter SARS- CoV-2 variants often harbor multiple point mutations, conferring one or more traits that provide an evolutionary advantage, such as increased transmissibility, immune evasion and longer infection duration. In a number of cases, variant emergence has been linked to long-term infections in individuals who were either immunocompromised or treated with convalescent plasma. In this paper, we explore the mechanism by which fitter variants of SARS-CoV-2 arise during long-term infections using a mathematical model of viral evolution and identify means by which this evolution can be slowed. While viral load and infection duration play a strong role in favoring the emergence of such variants, the overall probability of emergence and subsequent transmission from any given infection is low, suggesting that viral variant emergence and establishment is a product of random chance. To the extent that luck plays a role in favoring the emergence of novel viral variants with an evolutionary advantage, targeting these low-probability random events might allow us to tip the balance of fortune away from these advantageous variants and prevent them from being established in the population.

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Section: Introductionmentioning

confidence: 99%

“…During this process, further stochasticity is introduced by the low numbers of viral particles required to start an infection in a new host, which creates a narrow transmission bottleneck 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Controlling long-term SARS-CoV-2 infections is important for slowing viral evolution

Egeren

Novokhodko

Stoddard³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…A higher intrapatient evolution of SARS-CoV-2 yielding several tens of variants appears to be associated with prolonged replication, as frequently found in more severe cases, older individuals, and particularly immunocompromised patients [40,193,[246][247][248][249][250]280,281]. Nonetheless, in most SARS-CoV-2 infections, there is one dominant variant throughout the course of the disease and upon onward transmission [279]. Animal experiments on viral evolution and transmission suggest that within-host SARS-CoV-2 variation is predominantly influenced by genetic drift and purifying selection [282].…”

Section: Sars-cov-2 Mutates On a Low But Constant Level Yielding Mutant Variants Over Timementioning

confidence: 98%

“…In contrast to HIV-1, intra-patient evolution in SARS-CoV-2 is restricted to mostly <0.05% genetic distance. Differences in variant distribution between upper and lower respiratory tract have been observed; however, the number of minority variants per patient usually remains <30% based on only a few variants (Table 1) [40,[272][273][274][275][276][277][278][279]. A higher intrapatient evolution of SARS-CoV-2 yielding several tens of variants appears to be associated with prolonged replication, as frequently found in more severe cases, older individuals, and particularly immunocompromised patients [40,193,[246][247][248][249][250]280,281].…”

Section: Sars-cov-2 Mutates On a Low But Constant Level Yielding Mutant Variants Over Timementioning

confidence: 99%

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Duerr¹,

Jimenez²,

Dittmann³

2021

Preprint

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped, positive-stranded RNA viruses with envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics delineating their distinct strategies for efficient spread.

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“…In general, the SARS-CoV-2 genome changes at a steady mutational rate of 0.0008 substitutions per site per year. As a result, acute respiratory viral infections have low intra-host diversity 21,22 . However, there is compelling evidence that SARS-CoV-2 evolution is accelerated in the respiratory tract of persistently infected immunocompromised hosts, re ecting reduced selective immune pressure 6, [23][24][25][26] .…”

Section: Organ-speci C Sars-cov-2 Evolution In An Immunocompromised Patientmentioning

confidence: 99%

Organ-specific genome diversity of replication-competent SARS-CoV-2

Cleemput

Snippenberg

Lambrechts

et al. 2021

Preprint

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gripped the world for over a year1,2. SARS-CoV-2 impacts people on a broad clinical spectrum from asymptomatic to severe respiratory and systemic manifestations resulting in death3. In addition, intra-host SARS-CoV-2 genomic plasticity periodically leads to emergence of new virus variants with higher transmission capacities4–6. Autopsy series have revealed several pathways to death in COVID-19 patients, including respiratory and multi-organ failure, and evidence of SARS-CoV-2 in various organs besides the lungs7,8. However, these studies did not demonstrate the presence of infectious virus in extrapulmonary sites nor did they investigate viral intra-host evolution across multiple organs. Here we report a detailed virological analysis of thirteen postmortem COVID-19 cases that confirms two stages of fatal disease evolution based on disease duration and viral loads in lungs and plasma9. More importantly, the study is the first to provide proof of viremia and presence of replication-competent SARS-CoV-2 in extrapulmonary organs of an immunocompromised patient, accompanied by tissue-specific patterns of genome diversity in organ-resident SARS-CoV-2 populations. In parallel, potentially more transmissible and virulent strains were detected in multiple organs, including identification of mutations N501Y, T1027I, and Y453F in spike (S) protein. These mutations are hallmarks of more contagious United Kingdom (lineage B.1.1.7), South African (lineage B.1.351), Brazilian (lineage P1 and B.1.1.248) or mink variants4,10. Our results provide novel insights about the pathogenesis of SARS-CoV-2 and highlight that COVID-19 treatment and hygiene measures need to be tailored to specific needs of immunocompromised patients.

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SARS-CoV-2 within-host diversity and transmission

Cited by 356 publications

References 76 publications

Controlling long-term SARS-CoV-2 infections is important for slowing viral evolution

Controlling long-term SARS-CoV-2 infections is important for slowing viral evolution

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

Organ-specific genome diversity of replication-competent SARS-CoV-2

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