Non-pharmaceutical interventions and the emergence of pathogen variants

Abstract

Non-pharmaceutical interventions (NPIs), such as social distancing and contact tracing, are important public health measures that can reduce pathogen transmission. In addition to playing a crucial role in suppressing transmission, NPIs influence pathogen evolution by mediating mutation supply, restricting the availability of susceptible hosts, and altering the strength of selection for novel variants. Yet it is unclear how NPIs might affect the emergence of novel variants that are able to escape pre-existing immunity (partially or fully), are more transmissible, or cause greater mortality. We analyse a stochastic two-strain epidemiological model to determine how the strength and timing of NPIs affects the emergence of variants with similar or contrasting life-history characteristics to the wildtype. We show that, while stronger and timelier NPIs generally reduce the likelihood of variant emergence, it is possible for more transmissible variants with high cross immunity to have a greater probability of emerging at intermediate levels of NPIs. This is because intermediate levels of NPIs allow an epidemic of the wildtype that is neither too small (facilitating high mutation supply), nor too large (leaving a large pool of susceptible hosts), to prevent a novel variant becoming established in the host population. However, since one cannot predict the characteristics of a variant, the best strategy to prevent emergence is likely to be implementation of strong, timely NPIs.

Lockdowns and Selection Pressure: A Modelling Study

“…Putting together our results with those of Gurevich et al [7], Ashby and Thompson [2] and Nielsen et al [15], we conclude that interventions against COVID-19 might, under certain conditions, intensify the competition between variants in such a way that leads to a more resilient virus. Our conclusions may also apply to other viruses affected by the COVID-19 interventions, and more generally to any competition that may exist between them.…”

“…Very little attention has been given to the evolutionary impact of non-pharmaceutical interventions in general. Recent works addressing this topic in the context of the COVID-19 pandemic include the articles of Gurevich et al [7], Ashby and Thompson [2] and Nielsen et al [15]. Gurevich et al [7] examined the effect of testing and isolation on the evolution of SARS-CoV-2, finding that testing and isolation may act to reduce virulence.…”

“…They found that a higher testing rate can select for a test-evasive viral strain, even if that strain is less infectious than the competing detectable strain. Ashby and Thompson [2] argued that while stronger and timelier non-pharmacheutical interventions generally reduce the likelihood of variant emergence, it is possible for more transmissible variants to have a greater probability of emerging at intermediate levels of these interventions. Nielsen et al [15] considered the impact of lockdowns specifically, and found that lockdowns exert an evolutionary pressure which favours variants with lower levels of overdispersion.…”

Diagnostic testing and the evolution of detection avoidance by pathogens

“…The evolution of anti-microbial resistance (AMR) (Davies and Davies 2010) and vaccine escape (Restif and Grenfell 2007) are the most prominent examples. Yet pathogens can also evolve in response to non-pharmaceutical interventions (Ashby, Smith, and Thompson 2023). In particular, there is a growing body of evidence that many pathogens can readily evolve in response to diagnostic testing, but little is known about precisely how diagnostic testing affects selection for detection avoidance.…”

“…While much attention has been paid to the impact of pharmaceutical interventions on pathogen evolution, non-pharmaceutical interventions, such as diagnostic testing (Seth-Smith et al 2009; Feleke et al 2021) or reducing social mixing (Ashby, Smith, and Thompson 2023) may can also affect pathogen evolution. For example, routine surveillance of Clostridium Difficile in Costa Rica identified three variants which gave negative PCR test results, caused by deletion of the tcdC gene (Ramírez-Vargas et al 2018).…”