Genomic epidemiology of SARS-CoV-2 in the United Arab Emirates reveals novel virus mutation, patterns of co-infection and tissue specific host responses

Background: The United Arab Emirates is a major business hub with substantial amount of international travel. Like many other countries, it was greatly affected by the COVID-19 pandemic since late January 2020, with recurring waves of infection. This study aimed at combining genomic and epidemiological data to unravel the source of SARS-CoV-2 introduction, transmission and evolution in the country. Methods: We performed meta-transcriptomic sequencing of 1,067 nasopharyngeal swab samples collected from qRT-PCR positive COVID-19 patients in Abu Dhabi, UAE, between May 9th and June 29th 2020. We investigated the genetic diversity and transmission dynamics of the viral population and analyzed the infection and transmission potential of novel genomic clusters. Within-host SARS-CoV-2 genetic variation was analyzed to determine the occurrence and prevalence of multiple infections. Finally, we evaluated innate host responses during the prolonged period of local infection. Results: All globally known SARS-CoV-2 clades were identified within the UAE sequenced strains, with a higher occurrence of European and East Asian clades. We defined 5 subclades based on 11 unique genetic variants within the UAE strains, which were associated with no significantly different viral loads. Multiple infection of different SARS-CoV-2 strains was observed for at least 5% of the patients. We also discovered an enrichment of cytosine-to-uracil mutation among the viral population collected from the nasopharynx, that is different from the adenosine-to-inosine change previously observed in the bronchoalveolar lavage fluid samples. This observation is accompanied with an upregulation of APOBEC4, an under-studied putative cytidine-uridine editing enzyme in the infected nasopharynx. Conclusions: The genomic epidemiological and molecular biological knowledge obtained in the study provides new insights for the SARS-CoV-2 evolution and transmission. We highlight the importance of sustained surveillance of the virus mutation using genomic sequencing as a public health strategy. Keywords: SARS-CoV-2, meta-transcriptomic sequencing, novel mutations and subclades, co-infection, cyosine depletion, host RNA editing