Towards a Better Understanding of the Neurological Effects of Infection-Associated Chronic Illnesses (R01 - Clinical Trial Optional) | PAR 25 116

Opportunity Information: Apply for PAR 25 116

This NIH grant opportunity (PAR-25-116) uses the R01 mechanism to support research that clarifies how infections can lead to lasting neurological and mental health-related problems. The main focus is on infection-associated chronic illnesses where symptoms persist well beyond the initial infection, including post-acute sequelae of COVID-19 with neurological involvement (often referred to as Neuro-PASC or neurological long COVID). It also explicitly includes other conditions believed to have an infectious trigger or post-infectious course, such as post-treatment Lyme disease, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), and other post-viral fatigue syndromes. The overall aim is to move beyond description of symptoms and toward a better, mechanism-level understanding of what is happening in the nervous system and related biological systems that influence brain and behavior.

A central theme of the NOFO is the encouragement of studies that dig into biologically plausible, scientifically compelling pathways that could explain why some people develop persistent neurological or neuropsychiatric symptoms after an infection. The opportunity is broad in the sense that applications can focus on one condition, but it places particular value on projects that look for shared mechanisms across multiple post-infectious illnesses. In practice, that means NIH is signaling strong interest in research that can identify converging biology (for example, overlapping immune, vascular, autonomic, metabolic, or neuroinflammatory signatures) that might explain common symptom clusters such as cognitive dysfunction, fatigue, dysautonomia, headache, sleep disruption, mood changes, or other mental health-related manifestations. Even when a project is centered on a single diagnosis, it should be framed in a way that clearly ties the proposed biology to a post-infectious etiology rather than unrelated causes of similar symptoms.

The NOFO makes clear that several types of research designs are considered in-scope. Neurologically oriented clinical research is strongly emphasized, including basic experimental studies in humans (BESH), which typically involve intensive human phenotyping or experimental approaches aimed at understanding mechanisms rather than testing a large-scale clinical efficacy endpoint. Mechanistic clinical trials are also allowable (the announcement is labeled "Clinical Trial Optional"), particularly when they are designed to test a mechanistic hypothesis and accelerate progress toward effective treatments. The key is that the trial component should illuminate biological pathways that contribute to the development or persistence of illness, rather than functioning purely as a pragmatic effectiveness trial with minimal mechanistic measurement.

In addition to human studies, the opportunity explicitly welcomes preclinical work. That includes studies using animal models, cell culture systems, or human tissue-based models, as long as the scientific question remains anchored to post-infectious disease mechanisms relevant to these chronic conditions. This allows applicants to use controlled systems to probe causality, identify candidate pathways, test how infection or infection-triggered immune responses affect neural function, or evaluate interventions at a mechanistic level before or alongside human studies. Across all approaches, the common requirement is that the proposed work must be situated in the context of a post-infectious trigger or etiology.

From an applicant and eligibility standpoint, this is a discretionary NIH grant in the health category (CFDA 93.242 and 93.853), and it is open to a wide range of organizations. Eligible applicants include many levels of government (state, county, city/township, special districts), public and private institutions of higher education, independent school districts, tribal governments and tribal organizations, public housing authorities/Indian housing authorities, and both nonprofit and for-profit entities (including small businesses, though the mechanism is R01 rather than an SBIR/STTR). The NOFO also highlights inclusion of institutions and organizations that often participate in federal research funding programs, such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs). Faith-based and community-based organizations, regional organizations, U.S. territories or possessions, and non-U.S. (foreign) entities are also listed as eligible, signaling NIH interest in broad participation and potentially diverse study populations or international collaborations where scientifically justified.

Key administrative details included in the listing are the opportunity title "Towards a Better Understanding of the Neurological Effects of Infection-Associated Chronic Illnesses (R01 - Clinical Trial Optional)," the funding opportunity number PAR-25-116, and the original closing date of 2025-11-05. The award ceiling and expected number of awards are not specified in the provided source data, which often means applicants should rely on standard NIH R01 budgeting norms and ensure their scope and budget are well-justified and aligned with the complexity of the proposed work. Overall, the opportunity is positioned to fund rigorous, mechanism-driven research that can explain persistent neurological and mental health-related symptoms after infection and, importantly, generate insights that speed the path toward targeted, effective interventions.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Towards a Better Understanding of the Neurological Effects of Infection-Associated Chronic Illnesses (R01 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.853.
• This funding opportunity was created on 2024-10-17.
• Applicants must submit their applications by 2025-11-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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