Evolution of human respiratory virus epidemics

Area of Science:

• Epidemiology
• Mathematical Biology
• Evolutionary Medicine

Background:

• Pathogen evolution is often assumed to reduce virulence, but this is not always the case.
• Forecasting the case fatality rate (CFR) and disease burden of new pathogens like SARS-CoV-2 is critical.
• Existing models for predicting virulence evolution often rely on unvalidated trade-offs between CFR and infection rates.

Purpose of the Study:

• To develop and evaluate a mathematical framework for predicting pathogen virulence evolution.
• To investigate the kinetic constraints that influence the evolution of virulence in human respiratory viruses.
• To forecast the potential disease burden and evolutionary trajectory of SARS-CoV-2.

Main Methods:

• A compartment model was constructed with parameters for symptomatic isolation and duration of immunity.
• The model was evaluated at both short timescales and equilibrium.
• The model was applied to analyze human respiratory viruses including smallpox, SARS-CoV-2, and influenza.

Main Results:

• Kinetic constraints were identified: coordinated parameter variation decreased CFR and increased pathogen fitness, while independent variation decreased fitness.
• Highly virulent viruses (e.g., smallpox) are constrained by host behavior, while moderately virulent viruses (e.g., SARS-CoV-2) are constrained by immunity duration and CFR.
• SARS-CoV-2 is predicted to continue presenting a substantial disease burden, with herd immunity potentially unachievable without vaccination.

Conclusions:

• Human respiratory epidemic evolution is often kinetically constrained; reduced CFR should not be assumed.
• Interventions like partial isolation of symptomatic individuals can significantly impact epidemic dynamics and evolutionary trajectories.
• Vaccination may be essential for achieving herd immunity against viruses like SARS-CoV-2.