A theoretical exploration of the origin and early evolution of a pandemic.

A virus that can cause a global pandemic must be highly adaptive to human conditions. Such adaptation is not likely to have emerged suddenly but, instead, may have evolved step by step with each step favored by natural selection. It is thus necessary to develop a theory about the origin in order to guide the search. Here, we propose such a model whereby evolution occurs in both the virus and the hosts (where the evolution is somatic; i.e., in the immune system). The hosts comprise three groups - the wild animal hosts, the nearby human population, and farther-away human populations. The theory suggests that the conditions under which the pandemic has initially evolved are: (i) an abundance of wild animals in the place of origin (PL); (ii) a nearby human population of low density; (iii) frequent and long-term animal-human contacts to permit step-by-step evolution; and (iv) a level of herd immunity in the animal and human hosts. In this model, the evolving virus may have regularly spread out of PL although such invasions often fail, leaving sporadic cases of early infections. The place of the first epidemic (PL), where humans are immunologically naïve to the virus, is likely a distance away from PL. Finally, this current model is only a first attempt and more theoretical models can be expected to guide the search for the origin of SARS-CoV-2.