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dc.contributor.authorHahn, Georg
dc.contributor.authorWu, Chloe M.
dc.contributor.authorLee, Sanghun
dc.contributor.authorHecker, Julian
dc.contributor.authorLutz, Sharon
dc.contributor.authorHaneuse, Sebastien
dc.contributor.authorQiao, Dandi
dc.contributor.authorDemeo, Dawn
dc.contributor.authorTanzi, Rudolph
dc.contributor.authorChoudhary, Manish
dc.contributor.authorEtemad, Behzad
dc.contributor.authorMohammadi, Abbas
dc.contributor.authorEsmaeilzadeh, Elmira
dc.contributor.authorCho, Michael M.
dc.contributor.authorLi, Jonathan
dc.contributor.authorRandolph, Adrienne
dc.contributor.authorLaird, Nan
dc.contributor.authorWeiss, Scott
dc.contributor.authorSilverman, Edwin
dc.contributor.authorRibbeck, Katharina
dc.contributor.authorLange, Christoph
dc.date.accessioned2021-04-02T11:25:38Z
dc.date.issued2021
dc.identifier.citationHahn, Georg, Chloe M. Wu, Sanghun Lee, Julian Hecker, Sharon M. Lutz, et al. "Two mutations in the SARS-CoV-2 spike protein and RNA polymerase complex are associated with COVID-19 mortality risk." Pre-print, 2021.en_US
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37367144*
dc.description.abstractSARS-CoV-2 mortality has been extensively studied in relation to host susceptibility. How sequence variations in the SARS-CoV-2 genome affect pathogenicity is poorly understood. Association between whole-genome sequencing (WGS) of the virus and death in patients with SARS-CoV-2 is one potential method of early identification of highly pathogenic strains to target for containment. We analyzed 7,548 single stranded RNA-genomes of SARS-CoV-2 patients in the GISAID database and associated variants with mortality using a logistic regression. In total, evaluating 29,891 sequenced loci of the viral genome for association with patient/host mortality, two loci, at 12,053bp and 25,088bp, achieved genome-wide significance (p-values of 4.09e-09 and 4.41e-23, respectively). Mutations at 25,088bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Additionally, mutations at 12,053bp are within the ORF1ab gene, in a region encoding for the protein nsp7, which is necessary to form the RNA polymerase complex responsible for viral replication and transcription. Both mutations alter amino acid coding sequences, potentially imposing structural changes that could enhance viral infectivity and symptom severity, and may be important to consider as targets for therapeutic development. Identification of these highly significant associations, unlikely to occur by chance, may assist with COVID-19 early containment of strains that are potentially highly pathogenic.en_US
dc.language.isoen_USen_US
dc.relation.hasversionhttp://doi.org/10.1101/2020.11.17.386714en_US
dash.licenseLAA
dc.titleTwo Mutations in the SARS-CoV-2 Spike Protein and RNA Polymerase Complex Are Associated With COVID-19 Mortality Risken_US
dc.typeJournal Articleen_US
dc.description.versionAuthor's Originalen_US
dash.depositing.authorRandolph, Adrienne
dc.date.available2021-04-02T11:25:38Z
dash.affiliation.otherHarvard T.H. Chan School of Public Healthen_US
dc.identifier.doi10.1101/2020.11.17.386714
dash.contributor.affiliatedLutz, Sharon
dash.contributor.affiliatedHecker, Julian
dash.contributor.affiliatedHahn, Georg
dash.contributor.affiliatedLee, Sanghun
dash.contributor.affiliatedChoudhary, Manish
dash.contributor.affiliatedEsmaeilzadeh, Elmira
dash.contributor.affiliatedMohammadi, Abbas
dash.contributor.affiliatedLi, Jonathan
dash.contributor.affiliatedHaneuse, Sebastien
dash.contributor.affiliatedQiao, Dandi
dash.contributor.affiliatedEtemad, Behzad
dash.contributor.affiliatedLange, Christoph
dash.contributor.affiliatedLaird, Nan
dash.contributor.affiliatedRandolph, Adrienne
dash.contributor.affiliatedDemeo, Dawn
dash.contributor.affiliatedSilverman, Edwin
dash.contributor.affiliatedTanzi, Rudolph
dash.contributor.affiliatedWeiss, Scott


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