Figure 3
SARS-CoV-2 can acquire multiple mutations during infections with sustained viral replication. (A) Fitness valley crossing model for acquisition of multiple mutations. Intermediate states with fewer mutations (light grey) have lower fitness than the WT virus within individuals, while variants with a specific combination of two or three mutations (blue and red, respectively) have higher fitness. (B) Mean frequency of variants with a beneficial combination of two (blue) or three (red) mutations within individuals with long-term SARS-CoV-2 infection. (C) Probability of a beneficial combination of two mutations (blue line) to be present in at least one virion transmitted if transmission occurs anytime during infection. For (B) and (C), shaded areas represent ± SEM, n = 1000 simulations per condition. (D) Number of de novo double mutant infections that establish a surviving lineage when some COVID-19 patients shed live virus for more than 30 days after developing symptoms. Deleterious intermediates had a fitness cost of 0.05 and beneficial mutation combinations had a selective advantage of 0.2. Unless otherwise specified, simulation parameter values are those given in Table 1.
