Fig. 3: Frequencies of longitudinal variants and phylogenetic relationships for virus populations bearing six mutations in the spike protein.

a, At baseline, all six spike variants (Illumina sequencing) except for spike(ΔH69/ΔV70) were absent (less than 1% and fewer than 20 reads). Approximately two weeks after receiving two units of convalescent plasma, viral populations carrying spike(ΔH69/ΔV70) and spike(D796H) increased to frequencies of more than 80% but decreased significantly 4 days later. This population was replaced by a population bearing spike(Y200H) and spike(T240I), detected in two samples over a period of 6 days. These viral populations were then replaced by virus carrying spike(W64G) and spike(P330S), which both dominated at day 93. Following a third course of remdesivir and an additional unit of convalescent plasma, the spike(ΔH69/ΔV70) and spike(D796H) virus population re-emerged to become the dominant viral strain reaching variant frequencies of more than 75%. Pairs of mutations arose and disappeared simultaneously, indicating linkage on the same viral haplotype. C_t values from respiratory samples are indicated on the right y axis (black dashed line and triangles). In cases in which there were duplicate readings on the same day, to remain consistent, samples from nose and throat swabs were plotted. b, Maximum-likelihood phylogenetic tree of patient X1 with the day of sampling indicated. Spike mutations defining each of the clades are shown ancestrally on the branches on which they arose. On dates for which multiple samples were collected, these are indicated as endotracheal aspirate (ETA) and nose and throat swabs (N+T).