Immunological characteristics govern the changing severity of COVID-19 during the transition to endemicity

1AbstractAs prospects for eradicating CoV-2 dwindle, we are faced with the question of how the severity of CoV-2 disease may change in the years ahead. Will CoV-2 continue to be a pathogenic scourge that, like smallpox or measles, can be tamed only by ongoing vaccination, or will it join the ranks of mild endemic human coronaviruses (HCoVs)? Our analysis of immunological and epidemiological data on HCoVs shows that infection-blocking immunity wanes rapidly, but disease-reducing immunity is long-lived. We estimate the relevant parameters and incorporate them into a new epidemiological model framework which separates these different components of immunity. Our model recapitulates both the current severity of CoV-2 and the relatively benign nature of HCoVs; suggesting that once the endemic phase is reached, CoV-2 may be no more virulent than the common cold. The benign outcome at the endemic phase is contingent on the virus causing primary infections in children. We predict a very different outcome were a CoV like MERS (that causes severe disease in children) to become endemic. These results force us to re-evaluate control measures that rely on identifying and isolating symptomatic infections, and reconsider ideas regarding herd immunity and the use of immune individuals as shields to protect vulnerable groups.