Speaker
Description
A poorly understood phenomenon of the COVID-19 pandemic has been the regular switching between major variants that have the 69-70 deletion in Spike, which leads to dropout of the S gene during RT-PCR testing, and those that do not. However, the biological underpinnings for this switching are poorly understood.
We hypothesised that variants that share the same S-gene target failure (SGTF) pattern have higher levels of cross-immunity than those that do not, likely mediated through changes in viral structure caused by del69-70. To test the plausibility of this hypothesis, we developed an SIR-type ODE model, and an agent-based model (ABM), that each allow for different levels of immunity and cross-immunity, determined by the infection history of individuals, and can accommodate hundreds of introduced variants. The switching of SGTF was an emergent property of both models, with SGTF most likely to be observed when cross-immunity is moderately long-lasting, and where a large number of variants are introduced. Variants failed to reach significant frequencies if they had reproduction numbers, Rt <1 at time of emergence, and in the ABM due stochastic extinction. The models predict that timing of peaks of infection is driven by how fast cross-immunity wanes, whereas peak prevalence is driven by Rt at the time of variant emergence.
Analysis of sequence data, at both the between- and within-host levels, supported our hypothesis that SGTF switching is a consequence of the immunogenetic background at the time variants appear. If supported, this hypothesis has important consequences for vaccine design, in particular development of bi-valent vaccines incorporating variants with and without del69-70. It may also help predict when we would expect to see highly divergent new variants emerging, the timing of waves of infection, and how this links to peak prevalence.
