The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2

Abstract

In the fourth year of the COVID-19 pandemic, public health authorities worldwide have adopted a strategy of learning to live with SARS-CoV-2. This has involved the removal of measures for limiting viral spread, resulting in a large burden of recurrent SARS-CoV-2 infections. Crucial for managing this burden is the concept of the so-called wall of hybrid immunity, through repeated reinfections and vaccine boosters, to reduce the risk of severe disease and death. Protection against both infection and severe disease is provided by the induction of neutralizing antibodies (nAbs) against SARS-CoV-2. However, pharmacokinetic (PK) waning and rapid viral evolution both degrade nAb binding titers. The recent emergence of variants with strongly immune evasive potential against both the vaccinal and natural immune responses raises the question of whether the wall of population-level immunity can be maintained in the face of large jumps in nAb binding potency. Here we use an agent-based simulation to address this question. Our findings suggest large jumps in viral evolution may cause failure of population immunity resulting in sudden increases in mortality. As a rise in mortality will only become apparent in the weeks following a wave of disease, reactive public health strategies will not be able to provide meaningful risk mitigation. Learning to live with the virus could thus lead to large death tolls with very little warning. Our work points to the importance of proactive management strategies for the ongoing pandemic, and to the need for multifactorial approaches to COVID-19 disease control.

Antibody escape, the risk of serotype formation, and rapid immune waning: Modeling the implications of SARS-CoV-2 immune evasion

“…Understanding the potential of emerging strains to drive waves of infection, persist in circulation, and co-circulate with pre-existing strains is vital for understanding and reacting to this volatile phase of the pandemic. Immune evasion has implications for short-term and long-term transmission levels [ 33 ], possible changes in disease severity [ 34 ], and the efficacy of vaccines and therapeutics, especially monoclonal antibodies [ 22 , 35 ]. Anticipating the behavior of viral strains has tremendous practical significance for designing nonpharmaceutical and biomedical interventions.…”