Key Dates
July 8, 2024 - Notice of Intent to Publish a Funding Opportunity Announcement for Towards a Better Understanding of the Neurological Effects of Infection-Associated Chronic Illnesses (R01 - Clinical Trial Optional). See Notice NOT-NS-24-105.
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Mental Health (NIMH)
All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.
Office of Research on Women's Health (ORWH)
The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) intend to promote a new initiative by publishing a Notice of Funding Opportunity (NOFO) that solicits applications focused on the neurological and psychiatric manifestations of infection-associated chronic illnesses, including the post-acute sequelae of COVID-19 (Neuro-PASC) as well as other chronic illnesses with a potential infectious trigger (post-treatment Lyme Disease, myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS], postural orthostatic tachycardia syndrome [POTS], post-viral fatigue syndromes, etc.). Projects that investigate common neuropsychiatric mechanisms across multiple infection-associated chronic illnesses would be of particular interest, although this is not a requirement (i.e., applications can focus on a single condition).
This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.
The NOFO is expected to be published in Fall 2024 with an expected application due date in Winter 2025.
This NOFO will utilize the R21 activity code. Details of the planned NOFO are provided below.
Background
It has long been known that, in a subset of individuals acutely infected with certain pathogens, chronic sequelae can continue to persist (or develop de novo) long after the acute symptoms have resolved. Commonly referred to as infection-associated chronic illnesses, these conditions are often characterized by a failure to recover following an initial infection even though the original pathogen is no longer detectable using common analytic methods. Several prevalent chronic illnesses- including but not limited to ME/CFS, POTS/dysautonomia, post-treatment Lyme Disease (PTLD), fibromyalgia, mast cell activation syndrome (MCAS), and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS), among others- have long been suspected to have an infectious trigger in a certain subset of individuals. Importantly, such conditions tend to involve a core group of symptoms, many of which are neurological and/or neuropsychiatric (for example, extreme levels of fatigue, post-exertional malaise, neurocognitive impairment/brain fog, mood and anxiety disorders, orthostatic intolerance, unrefreshing sleep, headaches, and myalgia/arthralgia, among other symptoms).
While many infectious agents have been linked to the occurrence of infection-associated chronic illnesses, the COVID-19 pandemic has resulted in widespread interest in these phenomena. Recent epidemiological studies indicate that nearly one in five people infected with SARS-CoV-2 (the virus responsible for COVID-19) continue to experience a spectrum of symptoms beyond the acute phase, a condition now referred to as “Post-Acute Sequelae of COVID-19” (PASC) or “Long COVID”. Strikingly, there is a good deal of overlap between the neurological and psychiatric symptoms of PASC (Neuro-PASC) and other suspected infection-associated chronic illnesses such as ME/CFS and POTS, suggesting that these conditions might share an underlying pathophysiology. To date, ongoing work in the field has identified multiple mechanisms of interest that may be therapeutically targetable, including an ongoing exacerbated inflammatory response, microvascular and/or thromboembolic dysfunction, pathogen-induced autoimmunity, bioenergetic failure with metabolic and mitochondrial derangements, gut dysbiosis, and the reactivation of latent pathogens. A deeper understanding of how such mechanisms drive the neuropathophysiology of infection-associated chronic illnesses would greatly enhance ongoing efforts for therapeutic development.
Research Scope
This initiative will solicit R21 applications that propose to investigate the neuropathophysiological mechanisms of infection-associated chronic illnesses across the lifespan. Clinical research focused on scientifically compelling pathways that drive the neurological and psychiatric sequelae of infection-associated chronic illnesses (including basic experimental studies in humans (BESH) and/or mechanistic clinical trials) is within the scope of this initiative. Preclinical studies utilizing animal, cell culture, and/or human tissue models are also encouraged. All applications must propose mechanistic studies in the context of an infection.
Broad observational, epidemiological, and correlational studies without a significant mechanistic component will not be supported by this initiative (i.e., projects where the primary intent is to correlate patient-reported symptoms and/or neuropsychological testing with neuroimaging and/or other neurophysiological phenotypes without the interrogation of underlying mechanisms); and applications that propose clinical trials to test the efficacy, safety/tolerability, and/or pharmacodynamics of an intervention will be non-responsive.
Funding Information
TBD
The combined budget for direct costs for the two-year project period may not exceed $275,000. No more than $200,000 may be requested in a single year.
93.853
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Non-domestic (non-U.S.) Entity (Foreign Organization)
Regional Organization
Eligible Agencies of the Federal Government
Applications are not being solicited at this time.
Inquiries
Please direct all inquiries to:
William Daley, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email: william.daley@nih.gov
Leonardo Tonelli, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: leonardo.tonelli@nih.gov
Vicki Shanmugam, MBBS, MRCP, FACR, CCD
Office of Research on Women's Health (ORWH)
Telephone: 301-402-4179
Email: vicki.shanmugam@nih.gov
and Human Services (HHS)
