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MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes

Award Number: R01AI159260
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/13/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes - SUMMARY Located within the human Major Histocompatibility Complex (MHC) chromosome 6p21, the Human Leukocyte Antigen (HLA) region is the most medically important region of the human genome. Variation in the HLA region has been associated with over 150 diseases and conditions, including infectious disease, cancers, and major drug-hypersensitivities. While little is known at this point about the impact of host genetic factors in COVID-19, the epidemiology to-date reveals wide variation in disease course among confirmed cases of infection that does not appear to be fully explained by known risk factors. Because of its pivotal role in the immune response understanding the role of HLA variation promises to provide important insights relevant to understanding the immunopathogenesis of COVID-19, while informing vaccine development and potential immunotherapies. In Specific Aim 1, we will exploit an existing data resource, partnering with the National Marrow Donor Program and DKMS registries to collect data on COVID-19 symptoms, testing and outcomes using a novel, validated smartphone app in a very large sample (N=300,000-500,000) of volunteer bone marrow donors with pre-existing HLA genotyping data, allowing an extraordinarily well-powered examination of the role of these genes in disease. In Specific Aim 2, we will employ a novel, validated method for next-generation sequencing of the extended MHC (~5Mb), including all classical and non-classical HLA loci, as well as over 150 additional immune system loci, in large and diverse cohorts of COVID-19 patients (N=2000), as well patient cohorts with longitudinal clinical data and extensive immunoprofiling (N=300). Finally, in Specific Aim 3 we will contextualize these association studies through examination of the role of HLA presentation of SARS-CoV-2 antigens. In summary, we will leverage large and diverse patient cohorts alongside cutting edge technology and molecular biology to reveal the role of these important immune loci in COVID-19.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $785,611 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	5	6/25/2025	NON-COMPETING CONTINUATION	$785,611
														Subtotal = $785,611

Issue Date FY: 2024 ( Subtotal = $788,776 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	4	6/12/2024	NON-COMPETING CONTINUATION	$788,776
														Subtotal = $788,776

Issue Date FY: 2023 ( Subtotal = $791,948 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	3	6/16/2023	NON-COMPETING CONTINUATION	$791,948
														Subtotal = $791,948

Issue Date FY: 2022 ( Subtotal = $791,237 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	2	6/29/2022	NON-COMPETING CONTINUATION	$791,237
														Subtotal = $791,237

Issue Date FY: 2021 ( Subtotal = $809,466 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	1	7/13/2021	NEW	$809,466
														Subtotal = $809,466

Grand Total All Awards = $3,967,038

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MHC Variation in Host Response to SARS-CoV2 and COVID-19 Outcomes

Award Number: R01AI159260

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/13/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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