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

To unravel the source of SARS-CoV-2 introduction and the pattern of its spreading and evolution in the United Arab Emirates, we conducted meta-transcriptome sequencing of 1,067 nasopharyngeal swab samples collected between May 9th and Jun 29th, 2020 during the first peak of the local COVID-19 epidemic. We identified global clade distribution and eleven novel genetic variants that were almost absent in the rest of the world defined five subclades specific to the UAE viral population. Cross-settlement human-to-human transmission was related to the local business activity. Perhaps surprisingly, at least 5% of the population were co-infected by SARS-CoV-2 of multiple clades within the same host. 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 reported in the bronchoalveolar lavage fluid samples and a previously unidentified upregulation of APOBEC4 expression in nasopharynx among infected patients, indicating the innate immune host response mediated by ADAR and APOBEC gene families could be tissue-specific. The genomic epidemiological and molecular biological knowledge reported here provides new insights for the SARS-CoV-2 evolution and transmission and points out future direction on host-pathogen interaction investigation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Department of Health of Abu Dhabi, UAE and National Natural Science Foundation of China. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The overall research plan was reviewed and approved by the EthicsCommittees of BGI-Shenzhen (No. BGI-IRB 20143) and Department of Health of United Arab Emirates(DOH/CVDC/2020/1945) on the collect of SARS-CoV-2 virus. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes A total of 896 high quality consensus assemblies (with less than 2% gaps) were submitted to GISAID (EPI\_ISL\_698105-698169, EPI\_ISL\_698172-699161, EPI\_ISL\_708827-708838) and raw sequencing data aligned to the SARS-CoV-2 reference genome were uploaded to NCBI (PRJNA687136) . We combined our genomes with other publicly available sequences for a final dataset of 973 SARS-CoV-2 genomes(ncov_global.json, Supplementary file). The dataset can be visualized on the community Nextstrain page.