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Long COVID as a putative subtype of chronic fatigue syndrome

Award Number: R01AI170850
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: 08/18/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Long COVID as a putative subtype of chronic fatigue syndrome - Abstract A hallmark of infection with SARS-CoV-2 is the unpredictable variation in individual health response from those who are asymptomatic to those with life-threatening and refractory respiratory illness, and finally those with long lasting symptoms, here defined as Long COVID. The core symptoms of Long COVID are remarkably like chronic fatigue syndrome (CFS) with multisystem complaints including debilitating fatigue, fluctuating heart rate and headache. In CFS, an infectious trigger has been suspected but not proven and onset often follows flu-like symptoms. As disease mechanisms are not understood, the treatment options are currently symptomatic. Between 0.2-0.4% of the population suffer from CFS. The goal of this proposal is to elucidate the biological mechanisms and risk factors for Long COVID and test the hypothesis that Long COVID is a subtype of chronic fatigue syndrome. To elucidate potential mechanisms, we will use data from three different biobanks, a Long COVID genetics working group we have built and through a CFS consortium. In Aim 1, we will examine genetic risk factors and comorbidities through the Long COVID working group comprising 46 cohorts and over 1.5 million individuals. In addition, we will do a meta-analysis of CFS across three Biobanks (N = 740,000). This analysis will elucidate the connection between CFS and Long COVID and identify risk variants for both diseases. In Aim 2, we will explore contribution from immune molecules that fine tune response to pathogens. The immune defense relies on specific cells to prevent infection or to destroy viral and bacterial agents and the body's own infected cells alike. This aim will examine if the genetic variants that protect from infections, COVID-19, or comorbidities, predispose to Long COVID. We will specifically focus on those regions that have large explanatory power such as the human leukocyte antigen (HLA) in addition to exploring associations genome-wide at established COVID-19 loci. This aim will reveal which immune traits increase risk or protect from Long COVID and CFS, elucidating the type of immune responses responsible for disease development. In Aim 3, we will estimate heritability and shared genetic vs. environmental risk. We will estimate the proportion of environmental and genetic factors behind CFS and Long COVID through analysis of siblings, twins, and the general population in FinnGen and UK Biobank. This aim distinguishes the risk contribution from environmental risk and genetics in the context of a shared environment providing insight into the strength of shared environmental vs. genetic factors that are needed for disease development. The proposed work elucidates risk factors and comorbidities that contribute to CFS and Long COVID including the possibly shared disease etiology, symptomatology, and comorbidity. The project provides biological insights for future disease treatment and facilitates early disease diagnosis.


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 = $762,055 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	4	8/25/2025	SUPPLEMENT FOR EXPANSION	$412,109
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	8/11/2025	NON-COMPETING CONTINUATION	$349,946
														Subtotal = $762,055

Issue Date FY: 2024 ( Subtotal = $351,594 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	7/23/2024	NON-COMPETING CONTINUATION	$351,594
														Subtotal = $351,594

Issue Date FY: 2023 ( Subtotal = $353,193 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	8/9/2023	NON-COMPETING CONTINUATION	$353,193
														Subtotal = $353,193

Issue Date FY: 2022 ( Subtotal = $370,568 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	8/18/2022	NEW	$370,568
														Subtotal = $370,568

Grand Total All Awards = $1,837,410

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Long COVID as a putative subtype of chronic fatigue syndrome

Award Number: R01AI170850

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: 08/18/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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