Background

The prevalence of COVID-19 infections, the death rate of COVID-19 patients, the severity of COVID-19 symptoms, and the drug response of COVID-19 patients are reported to vary across different populations. Host factors such as ACE-2 has been shown to be an entry receptor for COVID-19 (Hoffmann Met al.,2020) and conflicting results on the possible association between blood type A and a higher risk for COVID-19 infection and mortality (Christopher AL et al., 2020, Zhao J et al., 2020).

In-silico analysis of viral-peptide-MHC class I binding affinity prediction showed some preliminary evidence correlations (Nguyen Aet al.,2020). Despite the fact that the number of COVID-19 tests performed and preventive measurements varies from countries to countries, the number of confirmed COVID-19 cases are significantly lower in East Asian countries including Japan comparing to European countries.

However, evaluation of COVID-19 host genetic susceptibility using large-scale population-based data and hypotheses-free genetic approaches such as Genome-Wide Association Studies (GWAS) or Whole Genome Sequencing (WGS) are essential to identify the whole host genetic susceptibility spectrum of COVID-19.

Around 80% of COVID-19 patients exhibit symptoms range from mild to asymptomatic; however, a small group of infected patients developed severe symptoms in a short time after infections. Currently, there is no systematic method to identify these potential severe symptoms patients from mild symptoms patients. Identification of genetic markers that contribute to COVID-19 severity could aid the hospital to prioritize the treatment of severe COVID-19 patients.

By June 2020 (https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/), there were 194 vaccine candidates and around 300 potential therapies for COVID-19 invarious stages of preclinical and clinical trials. Several potential post-infection therapies such as Remdesivir, Favipiravir, Lopinarvir and Avigan were entering the final stage of human testing. A collaboration effort between University of Oxford and pharmaceutical firm AstraZeneca have found that its COVID-19 vaccine (Pedro MF et al., 2020) could induce prolonged production of neutralizing antibodies with minor side effect that can be cured by paracetamol. On the other hand, Hydroxychloroquine was discontinued as several studies shown that it provided no therapeutic effect for COVID-19 patient. Integration of host genetic analysis could potentially maximize the drug’s efficacy and reduce the drugs adverse effect in COVID-19 patients.

Project Proposal

Blood collection

to be carried out in the National Center for Global Health and Medicine, Tokyo (Government appointed hospital for severe COVID-19 patients),and many other hospitals in Japan.

Host genetic susceptibility

analysis using WGS/GWAS and full-length sequencing of HLA class I and II genes.

COVID-19 pathogen

analysis using RNA sequencing.

Meta-analysis

with international research groups in identifying novel host genetic susceptibility which might be specified to a certain population or common susceptibilities that shared across populations.

Katsushi Tokunaga, PhD
Director of Genome Medical Science Project, National Center for Global Health and Medicine.
Professor Emeritus of the University of Tokyo

Charles Khor Seik-Soon, PhD
Project researcher of Genome Medical Science Project, National Center for Global Health and Medicine.

References

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.

Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, Thompson RF. Human leukocyte antigen susceptibility map for SARS-CoV-2. J Virol. 2020 Apr 17.pii: JVI.00510-20. doi: 10.1128/JVI.00510-20.

Zhao J, Yang Y, Huang H, Li D, Gu D, Lu X, Zhang Z, Liu L, Liu T, Liu Y, He Y, Sun B, Wei M, Yang G, Wang X, Zhang L, Zhou X, Xing M, Wang PG (2020) Relationship between the ABO blood group and the COVID-19 susceptibility. medRxiv.

Pedro M Folegatti, Katie J Ewer, Parvinder K Aley, Brian Angus, Stephan Becker, Sandra Belij-Rammerstorfer, Duncan Bellamy, Sagida Bibi, Mustapha Bittaye, Elizabeth A Clutterbuck, Christina Dold, Saul N Faust, Adam Finn, Amy L Flaxman,Bassam Hallis, Paul Heath, Daniel Jenkin, Rajeka Lazarus, Rebecca Makinson, Angela M Minassian, Katrina M Pollock, Maheshi Ramasamy, Hannah Robinson, Matthew Snape, Richard Tarrant, Merryn Voysey, Catherine Green, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Andrew J Pollard, Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 2020 Jul 20;S0140-6736(20)31604-4. doi: 10.1016/S0140-6736(20)31604-4.