Genomic Epidemiology of SARS-CoV-2 in the United Arab Emirates Reveals Novel Insights into the Virus Mutation, Co-Infection and Host-Dependent RNA Editing

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. Findings:  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 higher viral loads (p<0.001). Multiple infection of different SARS-CoV-2 strains was observed for at least 5% of the patients. We also observed a host-defense mechanism via RNA editing, likely mediated by APOBEC3 rather than ADAR in nasopharyngeal samples. Interpretation:  The SARS-CoV-2 epidemic in the UAE was founded by international importation followed by local transmission, leading to prevalent multiple infection and large subclade descendances. While RNA editing mechanisms mutate the viral population, newly arisen genetic variation can contribute to a heavier viral burden. Meta-transcriptomic sequencing can help to determine the transmission patterns of SARS-CoV-2. Funding:  Department of Health of Abu Dhabi, UAE and National Natural Science Foundation of China. Declaration of Interests: None to declare Ethics Approval Statement: The study was approved by the Abu Dhabi COVID19 Research IRB Committee (approval number DOH/CVDC/2020/1945).