Genotype-phenotype correlation identified a novel SARS-CoV-2 variant possibly linked to severe disease.

Publisher: Blackwell Verlag Country of Publication: Germany NLM ID: 101319538 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1865-1682 (Electronic) Linking ISSN: 18651674 NLM ISO Abbreviation: Transbound Emerg Dis Subsets: MEDLINE

Original Publication: Berlin : Blackwell Verlag

COVID-19*/epidemiology ; COVID-19*/veterinary ; SARS-CoV-2*/genetics; Animals ; Europe ; Female ; Genetic Association Studies/veterinary ; Humans

The geographic location and heterogeneous multi-ethnic population of Dubai (United Arab Emirates; UAE) provide a unique setting to explore the global molecular epidemiology of SARS-CoV-2 and relationship between different viral strains and disease severity. We systematically selected (i.e. every 100th individual in the central Dubai COVID-19 database) 256 patients by age, sex, disease severity and month to provide a representative sample of laboratory-confirmed COVID-19 patients (nasopharyngeal swab PCR positive) during the first wave of the UAE outbreak (January to June 2020). Sociodemographic and clinical data were extracted from medical records and full SARS-CoV-2 genome sequences extracted from nasopharyngeal swabs were analysed. Older age was significantly associated with COVID-19-associated hospital admission and mortality. Overweight/obese or diabetic patients were 3-4 times more likely to be admitted to hospital and intensive care unit (ICU). Sequencing data showed multiple independent viral introductions into the UAE from Europe, Iran and Asia (29 January-18 March), and these early strains seeded significant clustering consistent with almost exclusive community-based transmission between April and June 2020. Majority of sequenced strains (N = 60, 52%) were from the European cluster consistent with the higher infectivity rates associated with the D614G mutation carried by most strains in this cluster. A total of 986 mutations were identified in 115 genomes, 272 were unique (majority were missense, n = 134) and 20/272 mutations were novel. A missense (Q271R) and synonymous (R41R) mutation in the S and N proteins, respectively, were identified in 2/27 patients with severe COVID-19 but not in patients with mild or moderate disease (0/86; p = .05, Fisher's Exact Test). Both patients were women (51-64 years) with no significant underlying health conditions. The same two mutations were identified in a healthy 37-year-old Indian man who was hospitalized in India due to COVID-19. Our findings provide evidence for continued community-based transmission of the European strains in the Dubai population and highlight new mutations that might be associated with severe disease in otherwise healthy adults.
(© 2021 Wiley-VCH GmbH.)

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MBRU-CM-RG2020-04 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates

Keywords: COVID-19; Q271R; SARS-CoV-2; molecular phylogeny; mutation; whole genome sequencing

SARS-CoV-2 variants

Date Created: 20210128 Date Completed: 20220331 Latest Revision: 20240831

20240831

PMC8013505

10.1111/tbed.14004

33506644