Different mutations in SARS-CoV-2 associate with severe and mild outcome
| Autor: | Sándor Pongor, Ádám Nagy, Balázs Győrffy |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Male Exonuclease Mutation rate viruses 030106 microbiology RNA-dependent RNA polymerase Viral Nonstructural Proteins medicine.disease_cause Genome DNA sequencing Article Virus Viroporin Proteins 03 medical and health sciences Viral Proteins 0302 clinical medicine Mutation Rate high-risk death Coronavirus Nucleocapsid Proteins Humans Medicine Pharmacology (medical) 030212 general & internal medicine genome next generation sequencing Genetics chemistry.chemical_classification Mutation biology SARS-CoV-2 business.industry COVID-19 General Medicine COVID-19 Drug Treatment Hospitalization Infectious Diseases chemistry Phosphoprotein Multiple comparisons problem biology.protein Female business Glycoprotein |
| Zdroj: | International Journal of Antimicrobial Agents |
| Popis: | Highlights • A database of 4566 SARS-CoV-2 virus sequences and follow-up data was established • Mutations were mapped to amino acid changes for 3,733 non-silent mutations • Mutations correlated to mild outcome were located in the ORF8, NSP6, ORF3a, NSP4 and in the nucleocapsid proteins • Mutations associated with inferior outcome were located in the surface glycoprotein, in the RNA dependent RNA polymerase, in ORF3a, NSP3, ORF6 and in the nucleocapsid • Mutations leading to severe outcome with low prevalence were found in the ORF3A and in the NSP7 protein Introduction Genomic alterations in a viral genome can lead to either better or worse outcome and identifying these mutations is of utmost importance. Here, we correlated protein-level mutations in the SARS-CoV-2 virus to clinical outcome. Methods Mutations in viral sequences from the GISAID virus repository were evaluated by using “hCoV-19/Wuhan/WIV04/2019” as the reference. Patient outcomes were classified as mild disease, hospitalization and severe disease (death or documented treatment in an intensive-care unit). Chi-square test was applied to examine the association between each mutation and patient outcome. False discovery rate was computed to correct for multiple hypothesis testing and results passing FDR cutoff of 5% were accepted as significant. Results Mutations were mapped to amino acid changes for 3,733 non-silent mutations. Mutations correlated to mild outcome were located in the ORF8, NSP6, ORF3a, NSP4, and in the nucleocapsid phosphoprotein N. Mutations associated with inferior outcome were located in the surface (S) glycoprotein, in the RNA dependent RNA polymerase, in ORF3a, NSP3, ORF6 and N. Mutations leading to severe outcome with low prevalence were found in the ORF3A and in NSP7 proteins. Four out of 22 of the most significant mutations mapped onto a 10 amino acid long phosphorylated stretch of N indicating that in spite of obvious sampling restrictions the approach can find functionally relevant sites in the viral genome. Conclusions We demonstrate that mutations in the viral genes may have a direct correlation to clinical outcome. Our results help to quickly identify SARS-CoV-2 infections harboring mutations related to severe outcome. |
| Databáze: | OpenAIRE |
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