Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data

Abstract

The contours of endemic coronaviral disease in humans and other animals are shaped by the tendency of coronaviruses to generate new variants superimposed upon non-sterilizing immunity. Consequently, patterns of coronaviral reinfection in animals can inform the emerging endemic state of the SARS-CoV-2 pandemic. We generated controlled reinfection data after high and low risk natural exposure or heterologous vaccination to sialodacryoadenitis (SDAV) in rats. Using deterministic compartmental models, we utilized in vivo estimates from these experiments to model the combined effects of variable transmission rates, variable duration of immunity, successive waves of variants and vaccination on patterns of viral transmission. Using rat experiment-derived estimates, an endemic state achieved by natural infection alone occurred after a median of 724 days with approximately 41.3% of the population susceptible to reinfection. After accounting for translationally altered parameters between rat-derived data and human SARS-CoV-2 transmission, and after introducing vaccination, we arrived at a median time to endemic stability of 1437 (IQR = 749.25) days with a median 15.4% of the population remaining susceptible. We extended the models to introduce successive variants with increasing transmissibility and included the effect of varying duration of immunity. As seen with endemic coronaviral infections in other animals, transmission states are altered by introduction of new variants, even with vaccination. However, vaccination combined with natural immunity maintains a lower prevalence of infection than natural infection alone and provides greater resilience against the effects of transmissible variants. Significance Statement The pandemic to endemic trajectory of SARS-CoV-2 transmission will be shaped by the tendency of coronaviruses to elicit non-sterilizing immunity and generate new variants. We utilized estimates from controlled rat coronaviral infection in deterministic compartmental models to inform routes to endemic stability in SARS-CoV-2. We introduced translationally altered parameters to explore the effects of waning immunity, exposure to increasingly transmissible variants and successive vaccination. We arrived at an endemic state in which 15% of the population remains susceptible to reinfection. Similar to endemic coronaviral infections in other animals, transmission states are altered by introduction of new variants, even with vaccination. Accumulating and maintaining evolving immunity through vaccination and inevitable natural exposure is essential to achieving a stable endemic state.

SARS-CoV-2 elicits non-sterilizing immunity and evades vaccine-induced immunity: implications for future vaccination strategies

“…SARS-CoV-2 is on a pandemic-to-endemic trajectory with a strong seasonal transmission component. The long-term epidemiological pattern will be endemic persistence with peaks in transmission during the winter months plus recurrent surges of infection due to the emergence of novel variants [ 2 , 44 ]. There may be multi-year period troughs and peaks in incidence (longer than seasonal outbreaks) determined by transmission intensity (the magnitude of the basic reproductive number R 0 and the generation time of infection) and a population’s net birth rate (replenishing the supply of susceptible people) [ 2 , 44 , 45 ].…”

A C57BL/6 Mouse Model of SARS-CoV-2 Infection Recapitulates Age- and Sex-Based Differences in Human COVID-19 Disease and Recovery

“…The SARS-CoV-2 pandemic is moving towards an endemic phase and is likely to remain a persistent threat as the viral genome continues to evolve [ 17 ]. Viral evolution of SARS-CoV-2 leads to the continual emergence of new variants of concern replacing previous circulating variants [ 18 ], and also led to the ability of SARS-CoV-2 variants to infect mice [ 19 , 20 , 21 ].…”

“…Viral evolution of SARS-CoV-2 leads to the continual emergence of new variants of concern replacing previous circulating variants [ 18 ], and also led to the ability of SARS-CoV-2 variants to infect mice [ 19 , 20 , 21 ]. Additionally, current SARS-CoV-2 variants mediate a disease course that is much less pathogenic than the ancestral strain and has transitioned from causing a severe lower respiratory tract infection to a relatively mild upper respiratory tract infection [ 17 ]. Despite the lessened pathogenicity of newer SARS-CoV-2 variants, there remains a need to understand the processes underlying infection and recovery.…”

A C57BL/6 Mouse model of SARS-CoV-2 infection recapitulates age- and sex-based differences in human COVID-19 disease and recovery

“…The SARS-CoV-2 pandemic is moving towards an endemic phase and is likely to remain a persistent threat as the viral genome continues to evolve [15]. Viral evolution of SARS-CoV-2 leads to the continual emergence of new variants of concern replacing previous circulating variants [16], and also led to the ability of SARS-CoV-2 variants to infect mice [17][18][19].…”

“…Viral evolution of SARS-CoV-2 leads to the continual emergence of new variants of concern replacing previous circulating variants [16], and also led to the ability of SARS-CoV-2 variants to infect mice [17][18][19]. Additionally, current SARS-CoV-2 variants mediate a disease course that is much less pathogenic than the ancestral strain and has transitioned from causing a severe lower respiratory tract infection to a relatively mild upper respiratory tract infection [15]. Despite the lessened pathogenicity of newer SARS-CoV-2 variants, there remains a need to understand the processes underlying infection and recovery.…”