This conversation was led by Bernard Crespi, Canada Research Chair and Professor in the Department of Biosciences at Simon Fraser University. Zoonotic pandemics are evolutionary events comprising host shifts, speciation events, novel host-parasite interactions, and strong natural selection on both parasites and hosts. Bernard applied core principles of evolutionary medicine in the integration of information from three sources: (1) bat ecology, behavior and immune systems in the context of coevolution with viruses, (2) human immune responses to bat and non-bat viruses, and (3) symptoms, morbidity and mortality from COVID-19. He focused on transmission mechanisms, interferons, asymptomatic transmission, hyperinflammation, clotting, comparative biology and pathology of respiratory viruses, immunosenescence, and sex and age differences in risk of mortality. He concluded that most of the major medical and epidemiological features of COVID-19 can be understood in the context of mismatches between viral bat-adapted attack mechanisms and generalized human-evolved mechanisms of antiviral defense. These results have a variety of implications for research agendas, as well as for prevention and treatment of the infection.