(A) Timeline of specimen collection for each patient in each cohort relative to hospitalization. The dotted line indicates the hospitalization date, and the “X” (dark orange) indicates remdesivir administration date. (B) Overlaid histogram and distribution curves of the days between sample collection and hospitalization date for each cohort. (C) SARS-CoV-2 N1 Ct values for post specimens in each cohort as determined by qRT-PCR. Box-and-whisker plots represent the median (center line) and first/third quartiles (box), with tails extending 1.5 times the IQR. Statistical analysis was conducted using the Mann-Whitney U test, with P values indicated. (D) Shannon entropy across the genome of each isolate. Statistical analysis was conducted using a linear model while controlling for time between samples, viral load, and clade. (E) Mutational frequency at positions in nsp12 previously implicated in remdesivir resistance relative to the Wuhan-Hu-1 reference genome in the post specimen–only cohorts. Two additional positions identified from the analyses in Figure 4 are visualized on the right. Box-and-whisker plots represent the median (center line) and first/third quartiles (box), with tails extending 1.5 times the IQR. Only specimens with greater than 1% mutational frequency at a given position are shown (positions that were not detected are indicated as “ND”). (F) Shannon entropy at the same nucleotide positions as in E in the post specimen–only cohorts. Box-and-whisker plots represent the median (center line) and first/third quartiles (box), with tails extending 1.5 times the IQR. Statistical analysis was conducted using a linear model while controlling for time between samples and viral load (except for position 21771, which had too few data points to fit a model that also included viral load).