Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution

During the COVID-19 pandemic, human behavior change as a result of nonpharmaceutical interventions such as isolation may have induced directional selection for viral evolution. By combining previously published empirical clinical data analysis and multi-level mathematical modeling, we found that the SARS-CoV-2 variants selected for as the virus evolved from the pre-Alpha to the Delta variant had earlier and higher infectious periods but a shorter duration of infection. Selection for increased transmissibility shapes the viral load dynamics, and the isolation measure is likely to be a driver of these evolutionary transitions. In addition, we showed that a decreased incubation period and an increased proportion of asymptomatic infection were also positively selected for as SARS-CoV-2 mutated to the extent that people did not isolate. We demonstrated that the Omicron variants evolved in these ways to adapt to human behavior. The quantitative information and predictions we present here can guide future responses in the potential arms race between pandemic interventions and viral evolution. ### Competing Interest Statement The authors have declared no competing interest.