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Host cellular network governing the development of post SARS-CoV-2 tissue sequelae

Award Number: R01AI147394
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: 02/14/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2030

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Host cellular network governing the development of post SARS-CoV-2 tissue sequelae - Summary/Abstract The aftermath of the COVID-19 pandemic presents a significant public health challenge with over 60 million individuals globally affected by post-acute sequelae of SARS-CoV-2 infection (PASC). Through comparative single cell RNA-seq analysis, our prelim research has provided insights into the exuberant interactions of between monocyte-derived macrophages and lung resident T cells, mediated by the cytokine IFN-γ, in contributing to the development of respiratory PASC. Importantly, we found that the neutralization of IFN-γ ameliorated immune anomalies and chronic tissue sequelae after acute SARS-CoV-2 infection. Despite these advancements, critical knowledge gaps remain. The direct roles of T cell-derived IFN-γ in regulating post SARS-CoV-2 chronic diseases are yet to be fully understood. Our established post-viral tissue sequelae models are still relatively transient compared to human sequelae. Furthermore, the intricacies of the IFN-γ -STAT1 pathway in macrophages driving persistent tissue sequelae, and the potential of pharmacologically targeting this pathway to mitigate chronic sequelae post-infection are areas that need exploration. This grant application aims to address these gaps through three specific aims: Aim 1. To elucidate the roles of T cell-derived IFN-γ in post SARS-CoV-2 tissue sequelae. Aim 2. To determine the roles of persistent macrophage STAT1 signaling in driving post SARS-CoV-2 tissue sequelae. Aim 3. To examine the IFN-γ-STAT1-SPP1 axis in tissue inflammation and fibrosis post SARS-CoV-2 infection. The successful completion of this study promises to significantly advance our understanding of the cellular and molecular mechanisms driving respiratory PASC development. Moreover, it will open new avenues for developing effective therapeutics for PASC, addressing a crucial unmet clinical need.


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 = $642,689 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	002	6	6/10/2025	COMPETING CONTINUATION	$57
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	6	6/2/2025	COMPETING CONTINUATION	$642,689
2025	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	5	6/10/2025	NON-COMPETING CONTINUATION	-$57
														Subtotal = $642,689

Issue Date FY: 2024 ( Subtotal = $569,694 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	000	5	1/29/2024	NON-COMPETING CONTINUATION	$512,725
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	5	5/28/2024	NON-COMPETING CONTINUATION	$56,969
														Subtotal = $569,694

Issue Date FY: 2023 ( Subtotal = $569,694 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	003	4	1/4/2023	NON-COMPETING CONTINUATION	$569,694
2023	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	001	3	10/13/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$345,685
2023	2021	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	002	2	11/10/2022	SUPPLEMENT FOR EXPANSION	$0
2023	2021	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	2	10/13/2022	NON-COMPETING CONTINUATION	-$345,685
														Subtotal = $569,694

Issue Date FY: 2022 ( Subtotal = $569,694 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Allergy and Infectious Diseases Research	002	3	1/12/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$569,694
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	2	1/5/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	001	2	1/12/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $569,694

Issue Date FY: 2021 ( Subtotal = $966,944 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	002	2	2/18/2021	SUPPLEMENT FOR EXPANSION	$406,068
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	001	2	2/4/2021	NON-COMPETING CONTINUATION	$560,876
2021	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	1	12/2/2020	NEW	$0
														Subtotal = $966,944

Issue Date FY: 2020 ( Subtotal = $776,562 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	1	2/14/2020	NEW	$565,002
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	001	1	8/21/2020	SUPPLEMENT FOR EXPANSION	$211,560
														Subtotal = $776,562

Grand Total All Awards = $4,095,277

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Host cellular network governing the development of post SARS-CoV-2 tissue sequelae

Award Number: R01AI147394

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: 02/14/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2030

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