Evolution of resistance to COVID-19 vaccination with dynamic lockdown

Abstract

The COVID-19 pandemic has led to an unprecedented global response in terms of social lockdown in order to slow the spread of the virus 1,2. Currently the greatest hope is based on world-wide vaccination3,4. The expectation is that social and economic activities can gradually resume as more and more people become vaccinated. Yet, a relaxation of social distancing that allows increased transmissibility, coupled with selection pressure due to vaccination, will likely lead to the emergence of vaccine resistance 5. Here we analyze the evolutionary dynamics of COVID-19 in the presence of dynamic lockdown and in response to vaccination. We use infection and vaccination data of 6 different countries (Israel, US, UK, Brazil, France and Germany) to assess the probability and timing for the wave of vaccine resistant mutant2. For slow vaccination rates, resistant mutants will appear inevitably even if strict lockdown is maintained. For fast vaccination rates (such as those used in Israel) the emergence of the mutant can be prevented if strict lockdown is maintained during vaccination. Our mathematical results provide quantitative guidelines for a combined vaccination and lockdown policy that minimizes the probability of emergence of vaccine resistance variants for current and future vaccination programs.

A spatial vaccination strategy to reduce the risk of vaccine-resistant variants

“…Translating this number into a probability that escape will be avoided depends on our prior on 𝜇, namely what range of values do we view as being reasonable. Lobinska et al [38] provides a methodology to compute an upper bound based on the fact that a vaccine-resistant variant has not appeared until now in the highly vaccinated countries (which currently account for 5-10% of world population) and arrives at an estimate of about 10 -6 . However, without a lower bound it is hard to justify employing the spatial strategy.…”

“…On the optimistic side, none of the currently prevailing variants fully escapes the current vaccines [32,33], and it appears that most of them are simply improvements of the virus that are to be expected in its adaptation process in the human host. On the pessimistic side, this can be explained by the fact that mass vaccination, which leads to selective pressure for vaccine resistance, has taken place until recently only in countries that account for a small proportion of the world's population [37,38].…”

Evolutionary safety of death by mutagenesis

“…In our mathematical formalism, we describe the evolution of a virus within the body of a single human host by following the abundance of two viral types: wild type, 𝑥, and concerning mutants, 𝑦. Concerning mutants are those that can lead to undesirable viral evolution, for example to escape from vaccination (Nowak et al, 2021) or toward higher virulence or infectivity. Later we broaden the definition of variable 𝑦 to include any viable mutant, as these may subsequently facilitate epistatic tracks towards to VOCs.…”

Evolutionary safety of death by mutagenesis

“…The evolution of resistance of SARS-COV2 against vaccination or existing treatments as well as enhanced transmissibility or lethality is a major concern, which has given rise to an impressive number of studies [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] that have been founded on a long history of modelling the emergence of resistance against treatment in other viruses [28][29][30][31][32][33][34][35][36] and epidemiological models for disease spread 18,19,37,38 .…”

“…In our mathematical formalism, we describe the evolution of a virus within the body of a single human host by following the abundance of two viral types: wild type, x , and concerning mutants, y . Concerning mutants are those that can lead to undesirable viral evolution, for example to escape from vaccination 14 or toward higher virulence or infectivity. Later we broaden the definition of variable y to include any viable mutant, as these may subsequently facilitate epistatic tracks towards to VOCs.…”