- Supplement While little is known about the impact of host genetic factors on the risk for infection, morbidity and mortality in COVID-19, current epidemiology reveals wide variation in disease course among confirmed cases of infection that is not fully explained by known comorbidities and other risk factors. Because of its pivotal role in the immune response and long-established associations with disease phenotypes, Human Leukocyte Antigen (HLA) variation will likely be found to play a key role in COVID-19 outcomes. Understanding the role of HLA variation will provide important insights relevant to the immunopathogenesis of COVID-19, while also informing vaccine development and potential immunotherapies (e.g. T-cell based therapies). Because the complexity and extreme polymorphism of the HLA region make consolidation, equivalency, analysis, and biological interpretation of HLA data challenging, it is our view that a centralized resource that aggregates data from disparate sources and platforms and provides well-curated bioinformatics and analytical tools will serve to accelerate discovery. Under the parent grant we continue to develop a suite of tools and programs for the standardized analysis, collection, exchange and storage of immunogenetic data, and these tools are being widely adopted by the immunogenetics community. This supplement request will allow us to apply these tools toward the development and application of a pair of web resources. The first will centralize access to COVID-19-related HLA data and HLA data- management and analysis tools, creating a knowledge base and technical resource for HLA and immunogenetics research on the COVID-19 pandemic. As an initial step in advancing this vision, we have launched the hlacovid19.org website. The second resource will connect COVID-19 researchers and clinicians in need of HLA typing services with the immunogenetics laboratories that can provide them. As an early step toward this goal, we have formed the COVID-19 HLA & Immunogenetics Consortium to unite the global community of HLA and immunogenetics experts and leaders in support of these efforts, and harness the collective experience and expertise of the HLA and immunogenetics community as part of the global effort to combat this pandemic.

Public Health Relevance

The Human Leukocyte Antigen (HLA) genes display extremely high levels of variation compared to the rest of the human genome, and are central for understanding the genetic basis of disease and improving human health. The unified system of specialized software tools that we are building under the parent grant will be applied here to standardize the analysis, collection, exchange and storage of HLA data from ongoing studies worldwide related to COVID-19, making these immunogenomic data publicly available and easier to use for research in the global pandemic, as well as for improving patient therapies and developing vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI128775-07S1
Application #
10150497
Study Section
Program Officer
Bridges, Nancy D
Project Start
2020-05-13
Project End
2021-02-28
Budget Start
2020-05-13
Budget End
2021-02-28
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
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Ahmadov, Gunduz Ahmad; Govender, Denira; Atkinson, Mark Alvin et al. (2018) Epidemiology of childhood-onset type 1 diabetes in Azerbaijan: Incidence, clinical features, biochemistry, and HLA-DRB1 status. Diabetes Res Clin Pract 144:252-259
Misra, Maneesh K; Damotte, Vincent; Hollenbach, Jill A (2018) The immunogenetics of neurological disease. Immunology 153:399-414
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Amorim, Leonardo M; Santos, Tiago H S; Hollenbach, Jill A et al. (2018) Cost-effective and fast KIR gene-content genotyping by multiplex melting curve analysis. HLA 92:384-391
Mack, Steven J; Udell, Julia; Cohen, Franziska et al. (2018) High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis. Genes Immun :
Moore, Eugene; Grifoni, Alba; Weiskopf, Daniela et al. (2018) Sequence-based HLA-A, B, C, DP, DQ, and DR typing of 496 adults from San Diego, California, USA. Hum Immunol 79:821-822
Misra, Maneesh K; Damotte, Vincent; Hollenbach, Jill A (2018) Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and DRB1*15:03, with implications for multiple sclerosis. Genes Immun :
Pappas, D J; Lizee, A; Paunic, V et al. (2018) Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest. Pharmacogenomics J 18:367-376

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