The College of Health Sciences (CHS) COVID-19 Response and Research Committee continues to hold virtual research forums to discuss research being conducted at CHS towards COVID-19 response.
The 3rd forum was held on 21st July, 2020 where Prof. Peter Mungai, from the School of Medicine was the presenter.
Below is an abstract of his study titled: Identify the molecular-genetic mechanisms driving disparities inCOVID-19 presentation in Africa
Built on the success of a decade-long commitment to bring the benefits of the genomic revolution to address grassroots health care in Africa, with a focus on prostate cancer, the iDZOMO team will redirect a significant proportion of their efforts, to determine the demographic and genetic basis (both host and viral) of SARS-CoV-2/COVID-19 presentation in Africa, in a project called iDZOMO-COVID-19. Participants include iDZOMO study sites located in Kenya, Camaroon and South Africa. The aim of the project, to determine the molecular-genetic mechanism behind why some patients infected with SARS-CoV-2 remain asymptomatic for COVID-19, while others develop severe life-threatening COVID-19 disease. The outcomes of this project will directly impact decision making to slow circulation through risk evaluation and prevention plans, while providing critical data to enable treatment strategies. All data will be shared across the study sites and ultimately filtered into international databases and as such include Africa in global efforts.
Not everyone infected with SARS-CoV-2 coronavirus presents with COVID-19. Some remain asymptomatic, others may develop symptoms only days after infection, while others present with severe COVID-19 presentation. The latter includes: pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure and death [1,2]. Data from China suggests that up to 30% of cases present asymptomatically , while roughly 15% of present with severe COVID-19 . Both ends of the spectrum are problematic, as asymptomatic/mild cases can spread the disease unknowingly, while severe cases are at risk of death.
The aim of iDZOMO-COVID-19 research consortium is to address this disparity within Africa. As contributing factors may be viral and/or host, or a result of virus-host interaction which may or may not be further impacted by co-infections and environmental contributions, it is important that we tackle this problem by breaking down silo research and work together. As such, the iDZOMO-COVID-19 team will interrogate both the viral and host genomes and environment at both ends of the COVID-19 spectrum (asymptomatic to severe), using a genomic data-intensive high-throughput approach.
Who/What is iDZOMO?
The initiative of DZOMO [iDZOMO: https://www.idzomo.org] was founded in 2018 by three partner institutions in South Africa (University of Pretoria, lead by Riana Bornman), Kenya (University of Nairobi, led by Peter Ngugi) and Australia (Garvan Institute of Medical Research (GIMR), led by Vanessa Hayes), as an umbrella network that joins, not only two continents, Africa and Australia, but also three well-established projects including: (i) Diversity inclusive Genomics Study for Southern Africa (DiGS-SA) since 2008 (previously the Southern African Genome Project); (ii) Southern African Prostate Cancer Study (SAPCS) since 2008, and the (iii) East African Prostate Cancer Study (EAPCS) since 2018. The over-riding objective of iDZOMO: to bring the benefits of the genomic revolution to Africa and as such close the gap in health disparities - ‘from-grassroots-to-cutting-edge’ model. While iDZOMO is focused on prostate cancer health disparities, iDZOMO-COVID-19 will use its infrastructure and network to direct its efforts to understanding the molecular-genetic basis for disparities in COVID-19 presentation. As part of the iDZOMO-COVID-19, the team is excited to have Cameroon join the fight against this devastating disease.
Broad Aim of iDZOMO-COVID-19
Aim 1: To determine the frequency and evolution, as well as association with COVID-19 presentation, of SARS-CoV-2 subtypes across Africa, through whole virus genome sequencing using a long-range capture method.
Aim 2: To determine host genetic factors that are protecting versus promoting COVID-19 disease presentation, specifically severe disease, in Africa, through whole genome sequencing and data-intensive genome-wide variant interrogation.
Aim 3: To determine how host and viral genetic variants (from genomic data generated in Aims 1 and 2) interact to either promote or protect patients from COVID-19 presentation and severe disease within Africa.
Aim 4: To identify any potential blood-born pathogenic agents (co-infections) that either promote or protect African SARS-CoV-2 positive patients from COVID-19, through metagenomic analyses of non-human genomic data generated as a by-product of Aim 2.
Aim 5: Train the next generation of Africans in data-intensive genomic analyses through video-based training and inter-continental analytics, with the aim to empower local African scientists in the genomic revolution.
Aim 6: To make all data immediately available to local African researchers (via a consortium data transfer agreement) to ensure that specific research questions of relevance for Africa can be addressed in a timely fashion. To facilitate data sharing and research outcomes, topic-specific task forces will be created with topic leads taking responsibility for prompt dissemination of findings via open access rapid publications and industry participation.
Aim 7: To ensure that African data is included in global databases.
Patient recruitment and inclusion: Patients, over 18 years of age and diagnosed via RT-PCR as SARS-CoV-2 positive, will be consented and recruited via iDZOMO-COVID-19 Clinical Partners from participating clinics and hospitals in Kenya and South Africa. Patients will be further classified via their associated symptoms as asymptomatic, COVID-19 mild or COVID-19 sever (pO2/FIOP2 [P/F] ration <300; O2 saturation (SaO2) at rest <94%).
Associated epidemiology: A short 1-pager questionnaire including critical demographics and medical history data, will be completed at time of recruitment to capture associated environmental contributions.
Sample and processing: Samples collected will include blood (for host and metagenomic analyses) and nasopharyngeal (for viral analyses). Processing will take place in a PC2 laboratory, with host DNA and viral RNA shipped under appropriate ethics, export permits and Material Transfer Agreements (MTA’s) to the GIMR.
Genomic data generation: Host DNA will be whole genome sequenced (WGS) to a minimum of 30X coverage using the Illumina NovaSeq instrument at the GIMR. Viral RNA will be transcribed into cDNA and sequenced using Oxford Nanopore long-read sequencing at the GIMR.
Data processing, analysis and training: WGS data (both viral and host) will be processed through the established pipelines for genome alignments, variant calling and annotation within the Hayes Lab at GIMR, which is further supported by High Performance Computing (HPC) located at Australia’s National Compute Infrastructure (NCI) and the University of Sydney Informatics Hub (SIH), thus GIMR costly sequencing and data storage costs are covered. As at 1 May 2020, GIMR has generated over 100 SARS-CoV-2 complete genomes and tens of thousands of host genomes.
Data analysis and training: All data analysis will be performed as a group via the specific informatic topic teams, focusing on different aspects of the data analysis. The topic team approach will ensure training of African staff and students in analytics, a vital research tool of benefit to everyone in the era of COVID-19. We envisage weekly topic team meetings will move to biweekly post data generation.
Workflow and timelines: Ethics (IRB) approvals, export permits and updated MTAs would need to be expedited at primary sites in South Africa and Kenya, via building on established pipelines and workflows already in place. Recruitment will take place over a defined collection period, which is to be decided by the clinical partners at each recruitment site as they assess their local demands on health and infrastructure. Due to the nature and significance of the COVID-19 crisis, the research should not be limited by study power – the power of this study is inclusion, the more patients included the better the outcomes. In the meantime, the GIMR is seeking to secure funds to sequence the virus and host from the first 100 cases from Africa. We hope to achieve recruitment, data generation and analytics by the end of 2020.
The next session will be held on 28th July, 2020.
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