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

Link to article at PubMed

Transbound Emerg Dis. 2021 Jan 27. doi: 10.1111/tbed.14004. Online ahead of print.


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 quasi-randomly 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 (0/89; P=0.05, Fisher's Exact Test). Both patients were female (51-64 years) with no significant underlying health conditions. The same two mutations were identified in a healthy 37-year-old Indian male who was hospitalized in India due to COVD-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.

PMID:33506644 | DOI:10.1111/tbed.14004

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