<abstract><p>Three safe and effective vaccines against SARS-CoV-2 have played a major role in combating COVID-19 in the United States. However, the effectiveness of these vaccines and vaccination programs has been challenged by the emergence of new SARS-CoV-2 variants of concern. A new mathematical model is formulated to assess the impact of waning and boosting of immunity against the Omicron variant in the United States. To account for gradual waning of vaccine-derived immunity, we considered three vaccination classes that represent high, moderate and low levels of immunity. We showed that the disease-free equilibrium of the model is globally-asymptotically, for two special cases, if the associated reproduction number is less than unity. Simulations of the model showed that vaccine-derived herd immunity can be achieved in the United States <italic>via</italic> a vaccination-boosting strategy which entails fully vaccinating at least $ 59\% $ of the susceptible populace followed by the boosting of about $ 72\% $ of the fully-vaccinated individuals whose vaccine-derived immunity has waned to moderate or low level. In the absence of boosting, waning of immunity only causes a marginal increase in the average number of new cases at the peak of the pandemic, while boosting at baseline could result in a dramatic reduction in the average number of new daily cases at the peak. Specifically, for the fast immunity waning scenario (where both vaccine-derived and natural immunity are assumed to wane within three months), boosting vaccine-derived immunity at baseline reduces the average number of daily cases at the peak by about 90% (in comparison to the corresponding scenario without boosting of the vaccine-derived immunity), whereas boosting of natural immunity (at baseline) only reduced the corresponding peak daily cases (in comparison to the corresponding scenario without boosting of natural immunity) by approximately 62%. Furthermore, boosting of vaccine-derived immunity is more beneficial (in reducing the burden of the pandemic) than boosting of natural immunity. Finally, boosting vaccine-derived immunity increased the prospects of altering the trajectory of COVID-19 from persistence to possible elimination.</p></abstract>
India has been the latest global epicenter for COVID-19, a novel coronavirus disease that emerged in China in late 2019. We present a base mathematical model for the transmission dynamics of COVID-19 in India and its neighbor, Pakistan. The base model, which takes the form of a deterministic system of nonlinear differential equations, is parameterized using cumulative COVID-19 mortality data from each of the two countries. The model was used to assess the population-level impact of the control and mitigation strategies implemented in the two countries (notably community lockdowns, use of face masks, and social-distancing). Numerical simulations of the basic model indicate that, based on the current baseline levels of the control and mitigation strategies implemented, the pandemic trajectory in India is on a downward trend (as characterized by the reproduction number of the disease dynamics in India below, but close to, unity). This downward trend will be reversed, and India will be recording mild outbreaks (i.e., pandemic waves), if the control and mitigation strategies are relaxed from their current levels (e.g., relaxed to the extent that the associated community transmission parameters are increased by 20% or 40% from their current baseline values). Our simulations suggest that India could record up to 460,000 cumulative deaths by early September 2021 under the baseline levels of the control strategies implemented (up to 25,000 of the projected deaths could be averted if the control and mitigation measures are strengthened to the extent that the associated community transmission parameters are reduced by 20% from their baseline values). Our simulations show that the pandemic in Pakistan is much milder, with an estimated projected cumulative mortality of about 24,000 by early September 2021 under the baseline scenario. The basic model was extended to assess the impact of back-and-forth mobility between the two countries. Simulations of the resulting metapopulation model, which uses a Lagrangian mobility framework (based on residence-time spent in each country), shows that the burden of the pandemic in Pakistan increases with increasing values of the average time residents of India spend in Pakistan. In particular, it is shown that the India-to-Pakistan mobility pattern may trigger a significant fourth wave of the pandemic in Pakistan (under certain mobility scenarios and mitigation levels), with daily mortality peaking in mid-August to mid-September of 2021. It is also shown that extending the current travel restrictions by at least three months would significantly enhance the prospect of eliminating the pandemic in both countries. On the other hand, it is shown that, in addition to causing future multiple waves of the pandemic, easing the current levels of control and mitigation measures in the two countries (including travel restrictions) would result in delaying pandemic elimination in India and Pakistan to November and July 2022, respectively.
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