Ongoing Global and Regional Adaptive Evolution of SARS-CoV-2

Rochman, Nash D.; Wolf, Yuri I.; Faure, Guilhem; Mutz, Pascal; Zhang, Feng; Koonin, Eugene V.

doi:10.1101/2020.10.12.336644

Cited by 76 publications

(112 citation statements)

References 79 publications

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“…Diversification related to immune evasion commonly enables the maintenance of large virus populations over long time scales, as is the case for Influenza [34-36]. In the case of SARS-CoV-2, although immune evasion remains to be experimentally confirmed, diversification and host adaptation of SARS-CoV-2 have already been demonstrated [37-39]. Furthermore, products of virus genes that are specifically found in pathogenic beta-coronaviruses have been implicated in immunomodulation [40], suggesting that the virus adapts to maintain an endemic equilibrium in this way.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Human Respiratory Virus Epidemics

Rochman

Wolf

Koonin

2020

Preprint

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BackgroundWhile pathogens often evolve towards reduced virulence, many counterexamples are evident. When faced with a new pathogen, such as SARS-CoV-2, it is highly desirable to be able to forecast the case fatality rate (CFR) into the future. Considerable effort has been invested towards the development of a mathematical framework for predicting virulence evolution. Although these approaches accurately recapitulate some complex outcomes, most rely on an assumed trade-off between mortality and infectivity. It is often impractical to empirically validate this constraint for human pathogens.ResultsUsing a compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity, we reveal kinetic constraints where the variation of multiple parameters in concert leads to decreased virulence and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and Influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as Smallpox, are likely often constrained by host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR.ConclusionsThe evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in virulence should not be assumed. Our findings imply that, without continued public health intervention, SARS-CoV-2 is likely to continue presenting a substantial disease burden. The existence of a parameter regime admitting endemic equilibrium suggests that herd immunity is unachievable. However, we demonstrate that even partial isolation of symptomatic individuals can have a major effect not only by reducing the number of fatalities in the short term but also by potentially changing the evolutionary trajectory of the virus towards reduced virulence.

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Section: Discussionmentioning

confidence: 99%

Evolution of Human Respiratory Virus Epidemics

Rochman

Wolf

Koonin

2020

Preprint

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“…However, although diversification of the virus is apparent [24][25][26] and the potential for escape is being actively investigated 5,6,27,28 , it cannot be ruled out that all escape variants have a substantially reduced infectivity, represented by β<<1, in which case the highest possible vaccination rate will be optimal and the benefits specific to postvaccination contact limitation could be negligible.…”

Section: Limitationsmentioning

confidence: 99%

Substantial Impact of Post Vaccination Contacts on Cumulative Infections during Viral Epidemics

Rochman

Wolf

Koonin

2020

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BackgroundThe start of 2021 will be marked by a global vaccination campaign against the novel coronavirus SARS-CoV-2. Formulating an optimal distribution strategy under social and economic constraints is challenging. Optimal distribution is additionally constrained by the potential emergence of vaccine resistance. Analogous to chronic low-dose antibiotic exposure, recently inoculated individuals who are not yet immune play an outsized role in the emergence of resistance. Classical epidemiological modelling is well suited to explore how the behavior of the inoculated population impacts the total number of infections over the entirety of an epidemic.MethodsA deterministic model of epidemic evolution is analyzed, with 7 compartments defined by their relationship to the emergence of vaccine-resistant mutants and representing three susceptible populations, three infected populations, and one recovered population. This minimally computationally intensive design enables simulation of epidemics across a broad parameter space. The results are used to identify conditions minimizing the cumulative number of infections.ResultsWhen an escape variant is only modestly less infectious than the originating strain within a naïve population, there exists an optimal rate of vaccine distribution. Exceeding this rate increases the cumulative number of infections due to vaccine escape. Analysis of the model also demonstrates that inoculated individuals play a major role in the mitigation or exacerbation of vaccine-resistant outbreaks. Modulating the rate of host-host contact for the inoculated population by less than an order of magnitude can alter the cumulative number of infections by more than 20%.ConclusionsMathematical modeling shows that optimization of the vaccination rate and limiting post-vaccination contacts can affect the course of an epidemic. Given the relatively short window between inoculation and the acquisition of immunity, these results might merit consideration for an immediate, practical public health response.

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“…Despite accounting for roughly 25% of globally recorded COVID-19 cases, and approximately 20% of the available SARS-CoV-2 genome data, relatively few studies have detailed the introduction and emergence of SARS-CoV-2 lineages in the United States (Rochman et al, 2020;Worobey et al, 2020;Washington et al, 2021;Zeller et al, 2021). Furthermore, seroprevalence surveys indicate that between 1 in 10 and 1 in 3 people in the USA have already been infected with SARS-CoV-2, potentially high enough that selection for immune evasion may be present (Angulo, Finelli and Swerdlow, 2021;Bubar et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

Hodcroft

Domman

Snyder³

et al. 2021

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.

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Ongoing Global and Regional Adaptive Evolution of SARS-CoV-2

Cited by 76 publications

References 79 publications

Evolution of Human Respiratory Virus Epidemics

Evolution of Human Respiratory Virus Epidemics

Substantial Impact of Post Vaccination Contacts on Cumulative Infections during Viral Epidemics

Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

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