Sword of Damocles or choosing well. Population genetics sheds light into the future of the COVID-19 pandemic and SARS-CoV-2 new mutant strains

Alcaniz, Garcia Garcia de; Lopez-Rodas,; Costaş,

doi:10.1101/2021.01.16.21249924

Cited by 4 publications

(5 citation statements)

References 91 publications

(103 reference statements)

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“…The key triggers for this are not fully understood, but it is thought that the application of strict biosecurity measures may play a part by restricting the availability of new hosts. In such cases, the quasi-species becomes increasingly attenuated, with mutations accumulating via a mechanism called 'Muller's ratchet', to the point where the epidemic may die out [48]. This has been seen in many prior outbreaks of Ebola, where the infection became increasingly less pathogenic and less transmissible.…”

Section: Error Catastrophe Muller's Ratchet and Implications For Sars...mentioning

confidence: 99%

Tracking Co-Occurrence of N501Y, P681R, and Other Key Mutations in SARS-CoV-2 Spike for Surveillance

et al. 2022

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced five variants of concern (VOC) to date. The important spike mutation ‘N501Y’ is common to Alpha, Beta, Gamma, and Omicron VOC, while the ‘P681R’ is key to Delta’s spread. We have analysed circa 10 million SARS-CoV-2 genome sequences from the world’s largest repository, ‘Global Initiative on Sharing All Influenza Data (GISAID)’, and demonstrated that these two mutations have co-occurred on the spike ‘D614G’ mutation background at least 5767 times from 12 May 2020 to 28 April 2022. In contrast, the Y501-H681 combination, which is common to Alpha and Omicron VOC, is present in circa 1.1 million entries. Over half of the 5767 co-occurrences were in France, Turkey, or US (East Coast), and the rest across 88 other countries; 36.1%, 3.9%, and 4.1% of the co-occurrences were Alpha’s Q.4, Gamma’s P.1.8, and Omicron’s BA.1.1 sub-lineages acquiring the P681R; 4.6% and 3.0% were Delta’s AY.5.7 sub-lineage and B.1.617.2 lineage acquiring the N501Y; the remaining 8.2% were in other variants. Despite the selective advantages individually conferred by N501Y and P681R, the Y501-R681 combination counterintuitively did not outcompete other variants in every instance we have examined. While this is a relief to worldwide public health efforts, in vitro and in vivo studies are urgently required in the absence of a strong in silico explanation for this phenomenon. This study demonstrates a pipeline to analyse combinations of key mutations from public domain information in a systematic manner and provide early warnings of spread. The study here demonstrates the usage of the pipeline using the key mutations N501Y, P681R, and D614G of SARS-CoV-2.

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Section: Error Catastrophe Muller's Ratchet and Implications For Sars...mentioning

confidence: 99%

Tracking Co-Occurrence of N501Y, P681R, and Other Key Mutations in SARS-CoV-2 Spike for Surveillance

et al. 2022

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“…If random mutations can produce them, it is certain then (since the mighty size of SARS-CoV-2 population) that they have already happened. However, considering the specific characteristics of the SARS-CoV-2 population genetics, for these escape mutants to have a high likelihood of fixing within the population they need a tremendous selective advantage (close to 50%) 3 . Most likely, before massive vaccination takes place, these escape mutants will have less fitness and will be at very low numbers due to mutation-selection equilibrium.…”

Section: Figure 1 Response Of the Demand To A Change In The Price Of Vaccines Y Represents The Demand Of Vaccines (Yi At The Initial Momementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In 2019 SARS-CoV-2 could trespass animal-human barrier causing a catastrophic pandemic, it has proven to be a quick evolving virus and the arising of an escape mutant is certainly a potential risk 3 . Since COVID-19 is a global pandemic, only a global adequate vaccination strategy can minimize the likelihood of an escape mutant 3 . This is the reason why around 180 countries, with the support of the World Health Organisation, have signed the COVAX initiative to jointly negotiate the purchase and distribution of vaccine doses against SARS-CoV-2 4 .…”

Section: Introductionmentioning

confidence: 99%

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The `greed ́ and `nationalism ́ in vaccination against Covid-19 lead to the Tragedy of the Commons, Nash equilibrium and Giffen's goods, giving SARS-CoV-2 more opportunities to escape mutants.

Alcañiz¹,

López²,

RODAS³

et al. 2021

Preprint

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It is possible to follow an ideal vaccination global strategy, that will reduce to the minimum the number of infected and dead by COVID-19 as well as the likelihood of an escape mutant. This ideal vaccination strategy needs of a high degree of international cooperation among different countries. International initiatives as COVAX, advocated by the WHO, try to achieve such goal. However, in the present scenario with limited number of vaccine doses, Game Theory model also predicts that they are becoming goods subject to the Tragedy of the Commons. Countries with the capability to control vaccine dose distribution will desert from the international agreements, vaccinating first to their own nationals. If such behaviour is known by other countries (as is happening now) more countries will be tempted to desert as well. Eventually it will end in a Nash equilibrium, which stops the ideal vaccination strategy. Furthermore, in poorer countries, with great difficulties to get access to vaccine doses, these will be transformed into Giffen goods. Vaccination data available to date, show that we are in a scenario where vaccine doses have transformed into goods subject to the Tragedy of the Commons, countries desert from cooperation reaching a Nash equilibrium and vaccine doses are close to become a Giffen good for the poorer countries. This dynamic will not only rise the number of infected and dead by COVID-19, but also the likelihood of an escape mutant (in the SARS-CoV-2 populations) will be increased. If, eventually, this turns out to be the new scenario new vaccines could be developed for those new escape mutant strains, going back to a very similar setting as the starting one. Most likely, the world will reach a Pareto optimality (equilibrium between desertion and cooperation) due the pressure of those who seek high levels of cooperation to attain a global vaccination strategy.

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“…The key triggers for this are not fully understood, but it is thought that the application of strict biosecurity measures may play a part by restricting the availability of new hosts. In such cases, the quasispecies becomes increasingly attenuated, with mutations accumulating via a mechanism called 'Muller's ratchet', to the point where the epidemic may die out [41]. This has been seen in many prior outbreaks of Ebola, where the infection became increasingly less pathogenic and less transmissible.…”

Section: Sars-cov-2 Evolution and Selective Pressures On Quasispeciesmentioning

confidence: 99%

Cooccurrence of N501Y, P681R and other key mutations in SARS-CoV-2 Spike

Lee

Mangalaganesh

Wilson

et al. 2021

Preprint

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced five variants of concern (VOC) to date. The important Spike mutation N501Y is common to Alpha, Beta, Gamma and Omicron VOC, while the P681R is key to the spread of Delta. We have analysed circa 4.2 million SARS-CoV-2 genome sequences from the largest repository Global Initiative on Sharing All Influenza Data (GISAID) and demonstrated that these two mutations have cooccurred on the Spike D614G mutation background at least 3,678 times from 17 October 2020 to 1 November 2021. In contrast, the Y501-H681 combination, which is common to Alpha and Omicron VOC, is present in circa 1.1 million entries. Two-thirds of the 3,678 cooccurrences were in France, Turkey or US (East Coast), and the rest across 57 other countries. 55.5% and 4.6% of the cooccurrences were Alpha Q.4 and Gamma P.1.8 sub-lineages acquiring the P681R; 10.7% and 3.8% were Delta B.1.617.2 lineage and AY.33 sub-lineage acquiring the N501Y; the remaining 10.2% were in other variants. Despite the selective advantages individually conferred by N501Y and P681R, the Y501-R681 combination counterintuitively did not outcompete other variants in every instance we have examined. While this is a relief to worldwide public health efforts, in vitro and in vivo studies are urgently required in the absence of a strong in silico explanation for this phenomenon. This study demonstrates a pipeline to analyse combinations of key mutations from public domain information in a systematic manner and provide early warnings of spread.

show abstract

Sword of Damocles or choosing well. Population genetics sheds light into the future of the COVID-19 pandemic and SARS-CoV-2 new mutant strains

Cited by 4 publications

References 91 publications

Tracking Co-Occurrence of N501Y, P681R, and Other Key Mutations in SARS-CoV-2 Spike for Surveillance

Tracking Co-Occurrence of N501Y, P681R, and Other Key Mutations in SARS-CoV-2 Spike for Surveillance

The `greed ́ and `nationalism ́ in vaccination against Covid-19 lead to the Tragedy of the Commons, Nash equilibrium and Giffen's goods, giving SARS-CoV-2 more opportunities to escape mutants.

Cooccurrence of N501Y, P681R and other key mutations in SARS-CoV-2 Spike

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