key: cord-0701261-3uzau7if authors: Mak, Gannon C.K.; Lau, Angela W.L.; Chan, Andy M.Y.; Chan, Desmond Y.W.; Tsang, Dominic N.C. title: The D614G substitution in the S gene and clinical information for patients with COVID-19 detected in Hong Kong date: 2020-07-24 journal: J Clin Virol DOI: 10.1016/j.jcv.2020.104550 sha: 3ec25870246cc53b4af39d55fedfd3fc2a79df67 doc_id: 701261 cord_uid: 3uzau7if nan In an attempt to understand the relevance of D614G substitution among COVID-19 patients in Hong Kong, full length S gene sequences from severe and non-severe cases were examined. COVID-19 patients were confirmed by RT-PCR as described [12] . The severe cases were classified as described previously [13] . For this analysis, the original specimens of the respiratory samples from COVID-19 patients were sequenced using Sanger method. Only one specimen from each patient was included. The PCR amplification and DNA sequencing of the full length of S gene were performed using eight pairs of in-house designed primers (available on request). The SARS-COV-2 virus reference sequence, NC_045512 (GenBank accession number), was used in this analysis. From 22 Jan 2020 to 12 Jun 2020, a total of 113 cases were sequenced. Among them, 11 and 102 were severe and non-severe cases respectively. Of 11 severe cases, 4 (36.4%) showed D614G substitution while 39 (38.2%) non-severe cases showed D614G substitution. There is no association of D614G with severe illness (p=1.000, Fisher's exact test, doubled one-sided). Of the 49 cases (6 severe cases and 43 non-severe cases) sequenced between January and February, none of them showed D614G. The first case SARS-COV-2 is an RNA virus which evolves rapidly. It is interesting to see that the dominance of 614G virus is increasing over the 614D virus [14] [15] [16] . Although functional characteristics are unknown, numerous S gene mutations are reported regularly in GISAID [17] . It is thus important that laboratory surveillance continues to monitor the mutations of the S gene for SARS-COV-2 viruses. Concurrent genetic surveillance would facilitate early detection of sites that can increase mortality and J o u r n a l P r e -p r o o f infectivity as well as sites that are selected for the virus to escape immunological restraint especially when the vaccine is available. None. J o u r n a l P r e -p r o o f Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Could the D614G substitution in the SARS-CoV-2 spike (S) protein be associated with higher COVID-19 mortality? SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera Evaluation of rapid antigen test for detection of SARS-CoV-2 virus Association of D222G substitution in haemagglutinin of 2009 pandemic influenza A (H1N1) with severe disease Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 The SARS-CoV-2 Spike Protein D614G Mutation Shows Increasing Dominance and May Confer a Structural Advantage to the Furin Cleavage Domain