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The copyright holder for this preprint (which was not peer-reviewed) is the .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 24 despite the fact that it is still largely missing from current GISAID collection. This could 333 be due to the founding effect of mutations, in which case the T22303G mutation was not 334 transmitted out of the China during the early days; 3. The tri-nucleotide mutation in 335 ZJU-11 is unexpected; we note that this specific viral isolate is quite potent in our viral 336 load and CPE assay, and its patient remained positive for an astounding period of 45 days 337 and was only recently discharged from the hospital (Table 1) . Investigating the functional 338 impact of this tri-nucleotide mutation would be highly interesting. We note that in the 339 current database, another trinucleotide mutation (G28881A, G2882A and G28883C) has 340 been identified, which also results in two missense mutations at the protein level (Fig. S8) . 341 It leads to a cluster of more than 300 viral strains as of the time of writing this article, and 342 its mutational impact on the viral pathogenicity would be worth investigating. Finally, in 343 contrary to the recent report that a viable viral isolate could not be obtained from stool 344 samples, three of our viral isolated were extracted from stool samples, indicating that the 345 SARS-CoV-2 is capable of replicating in stool samples (Woelfel et al., 2020) . 346 In short, our study provides direct evidence that mutations currently occurring in the 347 SARS-CoV-2 genome have the functional potential to impact the viral pathogenicity. 348 Therefore, viral surveillance should be also performed at the cellular level when possible, 349 All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.