Monday, February 16, 2026 2/16/2026

REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (with Baricitinib) for Long COVID Related ADRD

Award Number: R01AG085873
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (with Baricitinib) for Long COVID Related ADRD - PROJECT SUMMARY/ABSTRACT Cognitive impairment, including Alzheimer’s Disease and Related Dementias (ADRD), and cardiopulmonary dysfunction following COVID-19, are components of the chronic syndrome known as Long COVID (LC). LC is an unprecedented public health crisis leading to cognitive, mental health, and functional disabilities for millions of people living in the United States and around the world. Large epidemiologic studies have demonstrated that the risk of ADRD increases multifold in many old and young patients following even mild SARS-CoV-2 infection. Patients with LC also frequently experience profound limitations in physical function and exercise intolerance that, when paired with ADRD, are life altering and result in inability to work and lead a family. Rapidly growing evidence links the clinical manifestations of LC to pathophysiologic mechanisms of abnormal inflammation and immune dysregulation. There is a driving, unmet need for robust clinical trials directly targeting immune dysregulation to reduce ADRD and cardiopulmonary injury related to LC. Our central hypothesis is that immunomodulators may be the most effective treatment for these sequelae of LC. Baricitinib is an immunomodulator (JAK1/2 inhibitor) that is FDA-approved to treat acute COVID-19 infection as well as certain autoimmune chronic diseases like rheumatoid arthritis. JAK1/2 signaling is a cardinal driver of both systemic and neuroinflammation. Our study, the Randomized trial EValuating Baricitinib on pERSistent nEurologic and Cardiopulmonary Symptoms of Long COVID (REVERSE-LC), will enroll 500 patients with LC and cognitive impairment at high risk for long-term ADRD across 4 sites to test the hypothesis that 6 months of baricitinib versus matched placebo will improve neurocognitive and physical function in LC. Aim 1 will measure the trajectory of neurocognitive function at enrollment, 6- and 12-months in baricitinib versus placebo patients using an objective neuropsychological battery as well as patient-reported cognitive function. Aim 2 will measure physical function using cardiopulmonary exercise testing and other functional measures in addition to patient-reported physical symptoms in patients treated with baricitinib versus placebo. Aim 3 will evaluate the effect of baricitinib versus placebo on plasma, cerebrospinal fluid, and neuroimaging inflammatory markers at enrollment, as well as 6- and 12-month follow-up study visits in patients with LC to identify inflammatory mediators of neuropsychological (ADRD) outcomes. The REVERSE-LC trial is novel in targeting immune dysregulation and inflammation for patients with LC and is based on our growing understanding of the mechanism of this emerging, post-infectious cause of rapidly-acquired ADRD risk. Regardless of the outcome of REVERSE-LC, this study will provide crucial insights into treatment of ADRD, sequelae of COVID, and disease pathogenesis. This investigation will also establish an innovative trial platform by which to test future interventions for rapidly-acquired neurocognitive dysfunction, cardiopulmonary disease, LC, and other age- related comorbidities leading to ADRD. It will advance the science of aging brain disease and disability.


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: 2026 ( Subtotal = $6,100,339 )
2026	2026	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	3	2/6/2026	NON-COMPETING CONTINUATION	$6,100,339
														Subtotal = $6,100,339

Issue Date FY: 2025 ( Subtotal = $6,107,805 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	2	3/14/2025	NON-COMPETING CONTINUATION	$5,609,208
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	001	2	6/18/2025	NON-COMPETING CONTINUATION	$498,597
														Subtotal = $6,107,805

Issue Date FY: 2024 ( Subtotal = $5,665,215 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Aging Research	000	1	12/26/2023	NEW	$5,665,215
														Subtotal = $5,665,215

Grand Total All Awards = $17,873,359

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REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (with Baricitinib) for Long COVID Related ADRD

Award Number: R01AG085873

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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