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George Githinji

Establishing a genomic sequencing platform to inform public health response of SARS-CoV-2 in an LMIC

George Githinji (KEMRI-Wellcome Trust Research Programme, Kenya) began his talk by describing how he and his team have been in the process of building a genomics platform for some time. They began the GeMVi project, with a grant from the National Institute of Health, which ‘formed the cornerstone of our capacity building for bioinformatics and genomics in East Africa’. Collaborating with institutes in Uganda and Tanzania, they leveraged and built on existing infrastructure for surveillance, wet lab sequencing, computing, and training programs. The project focused on viruses of importance to public health, working closely with ministers of health. When setting up for SARS-CoV-2 sequencing, the team utilised this existing platform, building on it further to generate genomic data to help inform public health response. George highlighted the research projects of four GeMVi fellows in East Africa, in which MinION sequencing is being used to provide data on viruses of public health importance.

George described how, when the first COVID-19 cases were confirmed in Kenya in March 2020, he and his colleagues needed to rapidly scale up the existing genomic sequencing infrastructure for the sequencing of SARS-CoV-2. Through partnerships with GeMVi, the ARTIC Network, and others, they were able to quickly set up for sequencing of the virus. Following confirmation of the first case on 17th March, SARS-CoV-2 samples arrived at their laboratory by the 21st. On 2nd April, they were able to sequence all eight SARS-CoV-2 genomes. George stressed that it was crucial to next ensure that these results were communicated with the relevant public health officials. At that time, measures were being implemented in Kenya to cap transmission, with heavy emphasis on testing but little on sequencing. George described how he and his colleagues realised that they were the only centre with the capacity to perform SARS-CoV-2 whole-genome sequencing at the time, and that expanding this capacity across other institutes was critical, to provide genomic data to characterise transmission of the virus. To do this, they set up training, scaling this up via their partnership with Africa CDC to train groups across the continent.

George then went into the different elements required in setting up a SARS-CoV-2 genomic sequencing platform: the sequencing itself, the bioinformatics pipeline, and the reporting. He showed the components they selected for each of these elements. For sequencing, they employed the ARTIC protocol for preparation of SARS-CoV-2 genomic libraries, which were then sequenced on a nanopore device, in a workflow taking ~14-18 hours end to end. In analysis, the basecalled data is demultiplexed and quality checked, then consensus genome assemblies are generated and polished. Using these consensus sequences, mutation profiling, phylogenetic analysis, and assignment of lineages is performed; this data is then reported and submitted. In total, this pipeline enables a turnaround time within ~7 days.

George noted that some samples were challenging due to their Ct values, and they performed optimisation to ensure they generated the required data.

George described how this SARS-CoV-2 sequencing pipeline enabled them to generate data informing genomic epidemiology early in the pandemic. Using this information, they were able to report on the early introductions of SARS-CoV-2 into Kenya, revealing routes of transmission across the border, locally, and associated with travel. Some of this work is published, with one manuscript currently under review. They were able to successfully scale up sequencing across other KEMRI institutes in Kenya, and they hope to expand further across the country. George noted that this has also involved other challenges, including obtaining SARS-CoV-2 samples and maintaining a cold chain. He described how, with partnerships with Africa CDC and the WHO Regional Office for Africa, they have also been able to support other countries across Africa in sequencing. Looking to the future, George noted the challenges presented by the ‘boom-and-bust’ nature of funding, important in obtaining the kits and reagents required for the workflow; they have been looking for long-term funding to ensure the resilience to sustain and further extend the genomic sequencing platform they have built.

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