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

Loney, Tom; Khansaheb, Hamda; Ramaswamy, Sathishkumar; Harilal, Divinlal; Deesi, Zulfa Omar; Varghese, Rupa Murthy; Belal Al Ali, Aydah; Khadeeja, Anees; Al Suwaidi, Hanan; Alkhajeh, Abdulmajeed; Mohamed AlDabal, Laila; Uddin, Mohammed; Al Faresi, Mubarak; Joshi, Madhvi; Senok, Abiola; Nowotny, Norbert; Alsheikh‐Ali, Alawi; Abou Tayoun, Ahmad

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.