![]() We also discuss the possibility that the virus will retain considerable virulence long term. We highlight the role of the dynamic interactions between changes in population immunity and ongoing viral evolution and immune escape in shaping the future association of SARS-CoV-2 with humans. We base our assessment on ongoing data from the COVID-19 pandemic and observations from previous epidemics. The goal of this Perspective is to discuss the probable transition to a new phase of SARS-CoV-2 infection in humans as an endemic pathogen, perhaps with intermittent epidemic peaks (Box 1). Thus, it is critical to consider what the new equilibrium between humans and this virus and its evolutionary descendants might be. In addition, although mass vaccine deployment may signal the end of the pandemic, the end of the pandemic does not necessarily equate to the end of SARS-CoV-2. However, two reasons temper our hope in reaching this conclusion: patchy vaccine coverage due to disparities in global access to vaccines and vaccine hesitancy, and vaccines may not always block virus transmission (despite reducing the burden of disease). With the ongoing deployment of several highly effective SARS-CoV-2 vaccines in many countries, there is an expectation that this virus will disappear. There are key pieces of data that are urgently needed in order to make good decisions we outline these and propose a way forward. Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS-CoV-2. Here we review relevant observations from previous epidemics and discuss the potential evolution of SARS-CoV-2 as it adapts during persistent transmission in the presence of a level of population immunity. ![]() Persistence of SARS-CoV-2 as an endemic virus, perhaps with seasonal epidemic peaks, may be fuelled by pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection and re-entries from zoonotic reservoirs. ![]() Although the trajectory is difficult to predict, the conditions, concepts and variables that influence this transition can be anticipated. Nonetheless, uncertainties remain about the type of long-term association that the virus will establish with the human population and, in particular, whether coronavirus disease 2019 (COVID-19) will become an endemic disease. There is a realistic expectation that the global effort in vaccination will bring the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under control.
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