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

Abstract

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.

Antigenic evolution of SARS-CoV-2 in immunocompromised hosts

“…The reason for this discrepancy is likely due to contrasting assumptions regarding within-host fitness, immunity, and traits under selection. For example, van Egeren et al [32] assume that a fitness valley exists at the within-host level with two or three mutations required to cross, whereas our model assumes that the fitness valley only exists at the between-host level (transmission) but may require many more mutations to traverse. If a fitness valley exists at the within-host level, then intuitively the importance of immunocompromised individuals for pathogen evolution will be lower.…”

Rapid relaxation of pandemic restrictions after vaccine rollout favors growth of SARS-CoV-2 variants: A model-based analysis

“…A number of newly emerged variants have been demonstrated experimentally to be more capable of infecting cells, spreading between hosts, and/or evading natural immunity, vaccines and therapeutics, compared to the original wild-type (WT) SARS-CoV-2 [ 8 – 10 ]. Once variants emerge within a population, they tend to expand rapidly and deterministically due to natural selection and dominate the local viral population in a relatively short period of time [ 11 ]. These variants have in a number of cases been associated with more severe disease outbreaks, and some variants have been demonstrated to be less susceptible to certain vaccines [ 8 , 9 , 12 , 13 ].…”

“…A case can be made that this public health outcome may in fact have been achieved successfully in some parts of the world, for example in Israel and Gibraltar [ 18 – 20 ], where high rates of vaccination were followed by a gradual relaxation of restrictions. Notably, the extermination of problematic viral variants due to stochastic events may be feasible even in the absence of herd immunity, provided viral transmission is low enough [ 11 , 21 ].…”

The specter of Manaus: the risks of a rapid return to pre-pandemic conditions after COVID-19 vaccine rollout

“…A number of newly emerged variants have been demonstrated experimentally to be more capable of infecting cells, spreading between hosts, and/or evading natural immunity, vaccines and therapeutics, compared to the original wild-type (WT) SARS-CoV-2 [9][10][11] . Once variants emerge within a population, they tend to expand rapidly and deterministically due to natural selection, and dominate the local viral population in a relatively short period of time 12 .…”

“…A case can be made that this public health outcome may in fact have been achieved successfully in some parts of the world, for example in Israel and Gibraltar [23][24][25] , where high rates of vaccination were followed by a gradual relaxation of restrictions. Notably, the extermination of problematic viral variants due to stochastic events may be feasible even in the absence of herd immunity, provided viral transmission is low enough 12,26 .…”