(A) Schematic of the data filtering pipeline used to identify paired specimens for whole-genome sequencing that span hospitalization date in the control cohort (blue) or remdesivir administration date in the remdesivir cohort (orange). (B) 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. (C) Overlaid histogram and distribution curves of the days between the pre and post samples for each cohort. (D) SARS-CoV-2 N1Ct values for the paired pre and 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. Specimens from the same patient are connected by lines. Statistical analysis for the paired samples within a cohort was conducted using Wilcoxon’s signed-rank test, and statistical analysis for the unpaired samples across cohorts was conducted using the Mann-Whitney U test, with P values indicated. (E) Phylogenetic tree of SARS-CoV-2 whole-genome sequences from each specimen in each cohort. Branch tips are colored by specimen type (pre versus post and cohort) and labeled by use of a randomized patient identifier. Gray patient labels denote identical consensus sequences in pre and post specimens, while black labels denote divergent sequences. Clade designations are specified on the outer ring. (F) Stacked bar chart showing the relative frequency of patients with identical (gray) versus divergent (black) pre and post sequences. The count is shown adjacent to each bar. (G) Hamming distance between paired pre and post specimens in each cohort depicted as a box-and-whisker plot representing 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 with a negative binomial distribution controlling for time between specimens.