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The copyright holder for this preprint (which was not peer-reviewed) is the .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 8 generating on average 245 million post-cleaning reads/67.16 Gb per sample (Table S1; 114 average coverage exceeding 2,000,000 X). This extraordinary depth is partially due to the 115 small genome of the SARS-CoV-2, which enables us to identify mutations with high 116 confidence. Moreover, in cases where the viral populations are not homogenous, the 117 depth could help us to characterize alleles with very low frequency. 118 In total, 33 mutations were identified (including 10 mutations observed in 119 mixed-populations), and 19 of these mutations were novel, according to the comparison 120 with 1111 genomic sequences available at GISAID on 3/24/2020 ( Fig. 1 , S1, and S2). 121 Specifically, G11083T and G26144T were found in ZJU-1, and both of these mutations 122 are known as founding mutations for a large group of viruses (Capobianchi et al., 2020) . 123 C8782T and T28144C were found in two of our viral isolates, ZJU-2 and ZJU-8, and 124 these two are known as the founding mutations for another large group of viral isolates 125 (Capobianchi et al., 2020) . Interestingly, mutation T22303G was found in five viral 126 isolates (ZJU-2, -5, -9, -10, and -11) and ZJU-5 and ZJU-9 were exposed to the same 127 potential source of infection during a business conference (Table 1) . Previously, only one 128 viral isolate identified in Australia had the T22303G mutation. Strikingly, the viral isolate 129 from patient ZJU-4, who attended the same conference as ZJU-5 and ZJU-9, has a novel 130 All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.