Do pathogens always evolve to be less virulent? The virulence-transmission trade-off in light of the COVID-19 pandemic.

The direction the evolution of virulence takes in connection with any pathogen is a long-standing question. Formerly, it was theorized that pathogens should always evolve to be less virulent. As observations were not in line with this theoretical outcome, new theories emerged, chief among them the transmission-virulence trade-off hypotheses, which predicts an intermediate level of virulence as the endpoint of evolution. At the moment, we are very much interested in the future evolution of COVID-19's virulence. Here, we show that the disease does not fulfill all the assumptions of the hypothesis. In the case of COVID-19, a higher viral load does not mean a higher risk of death; immunity is not long-lasting; other hosts can act as reservoirs for the virus; and death as a consequence of viral infection does not shorten the infectious period. Consequently, we cannot predict the short- or long-term evolution of the virulence of COVID-19.