Patient-derived mutations impact pathogenicity of SARS-CoV-2

Hangping Yao; Xiangyun Lu; Qiong Chen; Kaijin Xu; Yu Chen; Linfang Cheng; Fumin Liu; Zhigang Wu; Haibo Wu; Changzhong Jin; Min Zheng; Nanping Wu; Chao Jiang; Lanjuan Li

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.14.20060160 doi: medRxiv preprint 18 ZJU-11, decreased much faster than the others ( Fig. 3A and B) . At 48 hours P.I., we 263 observed small decreases for all viral isolates except for ZJU-10 and ZJU-11, both of 264 which had presumably already plateaued at 24 hours P.I. (Fig. 3A and B) . Notably, at 24 265 hours P.I., ZJU-2 and ZJU-8, members of the ORF-8-L84S cluster (majority of USA 266 WA-Seattle isolates are in this group), showed considerably lower viral loads (Fig. 4A) . 267 On the other hand, ZJU-1, which clusters with the S-D614G clade (mostly found in 268 Europe), has a viral load 19 times (2 4.25 ) higher than ZJU-2 and ZJU-8 (Fig. 4A) . In 269 addition, a near 270-fold difference (2 8.09 ) in viral load was observed between ZJU-10 270 and ZJU-2 at 24 hours P.I. (Fig. 4A ). These differences became statistically significant at their genomes, exhibit a significant variation of viral load when infecting Vero-E6 cells. 274 We next examined whether a higher viral load leads to more cell death (Fig. 4B) . 275 When examining these cell lines under a microscope at 48 hours and 72 hours P.I., the 276 CPE, or the cell death rate, are highly consistent with the viral load data ( Fig. 4C and author/funder, who has granted medRxiv a license to display the preprint in perpetuity.