Why are there so few (or so many) circulating coronaviruses?

Rice, Benjamin L.; Douek, Daniel C.; McDermott, Adrian B.; Grenfell, Bryan T.; Metcalf, C. Jessica E.

Despite vast diversity in non-human hosts and conspicuous recent spillover events, only a small number of coronaviruses have been observed to persist in human populations. This puzzling mismatch suggests substantial barriers to establishment. Here, we detail hypotheses that might contribute to explain the low numbers of endemic coronaviruses, despite their considerable evolutionary and emergence potential. We assess the possible explanations ranging from issues of ascertainment, historically lower opportunities for spillover, aspects of human demographic changes, as well as features of pathogen biology and pre-existing adaptive immunity to related viruses. We describe how successful emergent viral species must triangulate transmission, virulence, and host immunity to maintain circulation. Characterizing factors that might shape the limits of viral persistence can delineate promising research directions to better understand the combinations of pathogens and contexts most likely to lead to spillover.