Mathematical assessment of the roles of age heterogeneity and vaccination on the dynamics and control of SARS-CoV-2.

The COVID-19 pandemic, caused by SARS-CoV-2, disproportionately affected certain segments of society, particularly the elderly population (which suffered the brunt of the burden of the pandemic in terms of severity of the disease, hospitalization, and death). This study presents a generalized multigroup model, with heterogeneous sub-populations, to assess the population-level impact of age heterogeneity and vaccination on the transmission dynamics and control of the SARS-CoV-2 pandemic in the United States. Rigorous analysis of the model for the homogeneous case (i.e., the model with  = 1) reveal that its disease-free equilibrium is globally-asymptotically stable for two special cases (with perfect vaccine efficacy or negligible disease-induced mortality) whenever the associated reproduction number is less than one. The model has a unique and globally-asymptotically stable endemic equilibrium, for special a case, when the associated reproduction threshold exceeds one. The homogeneous model was fitted using the observed cumulative mortality data for the United States during three distinct waves (Waves A (October 17, 2020 to April 5, 2021), B (July 9, 2021 to November 7, 2021) and C (January 1, 2022 to May 7, 2022)) chosen to align with time periods when the Alpha, Delta and Omicron were, respectively, the predominant variants in the United States. The calibrated model was used to derive a theoretical expression for achieving vaccine-derived herd immunity (needed to eliminate the disease in the United States). It was shown that, using the one-group homogeneous model, vaccine-derived herd immunity is not attainable during Wave C of the pandemic in the United States, regardless of the coverage level of the fully-vaccinated individuals. Global sensitivity analysis was carried out to determine the parameters of the model that have the most influence on the disease dynamics and burden. These analyses reveal that control and mitigation strategies that may be very effective during one wave may not be so very effective during the other wave or waves. However, strategies that target asymptomatic and pre-symptomatic infectious individuals are shown to be consistently effective across all waves. To study the impact of the disproportionate effect of COVID-19 on the elderly population, we considered the heterogeneous model for the case where the total population is subdivided into the sub-populations of individuals under 65 years of age and those that are 65 and older. The resulting two-group heterogeneous model, which was also fitted using the cumulative mortality data for wave C, was also rigorously analysed. Unlike for the case of the one-group model, it was shown, for the two-group model, that vaccine-derived herd immunity can indeed be achieved during Wave C of the pandemic if at least 61% of the populace is fully vaccinated. Thus, this study shows that adding age heterogeneity into a SARS-CoV-2 vaccination model with homogeneous mixing significantly reduces the level of vaccination coverage needed to achieve vaccine-derived herd immunity (specifically, for the heterogeneous model, herd-immunity can be attained during Wave C if a moderate proportion of susceptible individuals are fully vaccinated). The consequence of this result is that vaccination models for SARS-CoV-2 that do not explicitly account for age heterogeneity may be overestimating the level of vaccine-derived herd immunity threshold needed to eliminate the SARS-CoV-2 pandemic.