Notice of Intent to Publish a Funding Opportunity Announcement for Understanding Neurological Effects of COVID-19 and Post-Acute Sequelae of SARS-CoV-2 Infection (R01 Clinical Trial Optional)

Key Dates

NOT-OD-22-195 - New NIH "FORMS-H" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2023

NOT-OD-22-189 - Implementation Details for the NIH Data Management and Sharing Policy

NOT-OD-22-198 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023

NOT-OD-23-012 - Reminder: FORMS-H Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available

NOT-NS-23-069 - Notice of Intent to Publish a Funding Opportunity Announcement for Understanding Neurological Effects of COVID-19 and Post-Acute Sequelae of SARS-CoV-2 Infection (R21 Clinical Trial Optional)

National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Aging (NIA)

National Institute of Mental Health (NIMH)

National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH) and the   National Institute on Aging (NIA) intend to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to invite applications focused on the neurological and neuropsychiatric manifestations of COVID-19 (neuro-COVID) and Post-Acute Sequelae of SARS-CoV-2 Infection (neuro-PASC) and on the effect of COVID-19 on pre-infection neurologic conditions. Applications investigating the pathophysiology and mechanisms of neuro-COVID and neuro-PASC and neurologically-focused human subjects research, as well as those proposing studies of scientifically compelling pathways to prevent the development of neuro-PASC or to accelerate the development of effective treatments for PASC-related neurological complications are of particular interest for this FOA. 

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. 

The FOA is expected to be published in the first quarter of 2023 with an expected application due date in late Spring 2023.

This FOA will utilize the R01 activity code. Details of the planned FOA are provided below.

National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH) and the  National Institute on Aging (NIA) intend to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to invite applications focused on the neurological and neuropsychiatric manifestations of COVID-19 (neuro-COVID) and Post-Acute Sequelae of SARS-CoV-2 Infection (neuro-PASC) and on the effect of COVID-19 on pre-infection neurologic conditions. Neurological conditions are extremely common in people diagnosed with COVID-19. It has been reported that more than 80% of hospitalized patients have at least one neurological condition. There is evidence that more than half of the people infected with COVID-19 continue to experience a spectrum of symptoms beyond the acute phase, a condition termed “Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)” and colloquially known as Long COVID. Similar to acute COVID, neurological and neuropsychiatric symptomatology, including brain fog (cognitive, attention, and concentration disability), dysautonomia, mood disorders, anxiety and headache, are characteristic of PASC. There is also growing evidence that COVID-19 may increase the risks of neurological conditions like Alzheimer’s disease, movement disorders, and epilepsy in the long term. However, specific mechanisms underlying the development of neurological and psychiatric symptoms and the impact of Sars-CoV2 on the nervous system continue to be poorly understood, creating a major obstacle for the identification of effective prevention and treatment approaches. The purpose of these RFAs is to fill the gaps in knowledge on COVID and the nervous system. 

NINDS 

The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all people. The purpose of this Funding Opportunity Announcement (FOA) is to invite research applications focused on the neurological manifestations of COVID-19 (neuro-COVID) and Post-Acute Sequelae of SARS-CoV-2 Infection (neuro-PASC) and on the effect of COVID-19 on pre-infection neurologic conditions. NINDS will accept applications investigating the pathophysiology and mechanisms of neuro-COVID and neuro-PASC as well as mechanistic clinical trials. While applications proposing studies of scientifically compelling pathways to prevent the development of neuro-PASC or to accelerate the development of effective treatments for PASC-related neurological complications are of particular interest for this FOA, clinical trials that seek to answer specific questions about interventions or treatment safety, tolerability or efficacy will NOT be supported under this FOA.  Please refer to NINDS Funding-Opportunities to find the appropriate NIH or NINDS-specific FOA for such clinical trials. In many cases, small interventional trials exploring an intervention are within scope of PAR-22-142. NINDS Exploratory Clinical Trials (U01 Clinical Trial Required).  This FOA is intended to support R01 research project grants that are adequately powered and of sufficient scope to examine the pathophysiology of neuro-COVID, neuro-PASC and mechanistic clinical trials. NINDS strongly encourages applicants to consult with NINDS Program Officials to ensure the suitability of the application for this FOA.

For the purposes of this RFA, the NINDS has interest in:

• Identification of mechanisms of central nervous system (CNS) and peripheral nervous system (PNS) manifestations of COVID-19 and PASC.
• Identification of persistent SARS-CoV-2 reservoirs and evidence of chronic immune dysregulation or viral re-activation in relation to neurologic symptomatology.
• Research on CNS or PNS-specific tissue-associated autoantibodies and correlation with neurologic clinical parameters including severity and duration of symptoms.
• Longitudinal correlation of specific inflammatory biomarkers and PASC-related neurological complications.
• Research evaluating brain endothelial dysfunction, coagulopathy and vasculopathy and the effects of potential protective agents on neurologic symptoms.
• Development and validation of biomarkers of mitochondrial dysfunction in PASC that may relate to neurologic symptoms.
• Research to better understand the neuropathobiology of COVID-19 and PASC in the context of SARS-CoV-2 variants.
• Understanding overlapping mechanisms of COVID-19/PASC and other chronic conditions with similar neurologic symptomatology, such as myalgic encephalomyelitis/chronic fatigue (ME/CFS) syndrome, Ebola, Lyme disease, HIV, Epstein-Barr virus, or connective tissue disorders.
• Studies to better understand the impact of SARS-CoV-2 on pre-existing neurological conditions such as multiple sclerosis, migraine, epilepsy, stroke, dementia, and traumatic brain injury 
• Development and validation of animal models replicating neuro-PASC. 
• Neuropathological studies of COVID-19 and the contribution of tissue damage by SARS-CoV-2 to PASC-related neurological complications. 

NIMH

For this FOA, the NIMH is interested in supporting mental health research questions related to SARS-CoV-2 Infection and those arising from Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). NIMH research areas of interest include 1) exploring mechanisms and pathophysiology of SARS-CoV-2 infection and PASC contributing to new and worsening mental illness outcomes, 2) identifying modifiable targets uniquely or robustly implicated in SARS-CoV-2 infection and PASC and relevant to new and worsening mental illness, and 3) conducting mechanistic trials probing the biological or behavioral processes of those targets that may be pursued in future mental health therapeutic development. Basic and translational research are relevant but note that for this FOA, NIMH only allows mechanistic clinical trials (see NOT-MH-20-105 Consolidated Notice on NIMH Clinical Trial Policies and related announcement for intervention development). NIMH is not accepting clinical trials to develop or test therapeutic interventions through this FOA. Applicants interested in evaluating treatments for clinical efficacy should apply through one of the NIMH FOAs listed at the Support for Clinical Trials at NIMH web page, which includes links to the NIMH clinical trials FOAs and Applicant FAQs. Applications that propose a clinical trial for the purpose of testing the safety and/or clinical efficacy of novel interventions are outside of the scope of NIMH research interests for this FOA and will not be supported through this FOA.  Projects focused on broad neurological effects (including brain fog, general memory deficits, and general neural functioning) outside of the context of mental illness should be directed to NINDS. Projects focused on mental illness (including psychosis, depression, anxiety) should be directed to NIMH. NIMH strongly encourages applicants to consult with NIMH Program Officials when developing plans for an application. This early contact will provide an opportunity to clarify NIMH policies and guidelines and identify whether the proposed project is consistent with NIMH mission and program priorities.

For the purposes of this RFA, the NIMH has interest in:

• Research establishing experimental systems to model SARS-CoV-2 CNS infection contributing to mental illness specifically and/or mental health related outcomes.
• Studies of SARS-CoV-2-specific maternal immune responses and signaling in CNS development and function in offspring.
• Studies of the mechanisms of SARS-CoV-2 and PASC affecting brain endothelial cells, brain lymphatics and glial cells responsible for triggering cognitive and emotional deficits, including the impact of stress, hormonal influences as well as sex effects in experimental systems relevant to mental illness.
• Studies to understand the impact of SARS-CoV-2 on the neuro-immune milieu and the resulting disruption of neuronal circuits, function, or behavior relevant to mental health.
• Studies to identify mechanisms by which people with mental illness are at increased risk of SARS-CoV-2 infection and death.
• Mechanistic clinical trials (see NOT-MH-20-105) to probe the relevance of therapeutic targets uniquely or robustly implicated specific to COVID-19 and mental illness.
• Studies to clarify the role of SARS-CoV-2 CNS infection and mental illness in PASC.
• Studies elucidating the pathogenesis of the mental illness characteristic of PASC.
• Host and environmental factors and the associated biological pathways that mediate the intensity and duration of mental illness dimensions of PASC, and affect recovery. 

 NIA 

NIA encourages applications under this FOA that address research questions central to NIA’s mission of improving the health and well-being of older adults through research.  Specific areas of interest include, but are not limited to: 

• Research on mechanisms underlying neurological and neurocognitive symptoms and sequelae of SARS-CoV-2 infection in older adults across the full range of illness severity (e.g., early alterations in sensory function, delirium, neuropsychiatric symptoms). 
• Studies to better understand the impact of SARS-CoV-2 on pre-existing age-related neurodegeneration, including AD/ADRD. 
• Studies of the role of brain barriers in preventing SARS-CoV-2 from gaining access to neural tissues in the context of aging and age-related neurodegeneration; mechanisms through which SARS-CoV-2 compromises brain barriers and propagates in the central nervous system (CNS).
• Research on genetic risk or protective factors that may alter cognitive function in older adults who have been afflicted with COVID-19.
• Neuropathological studies of COVID-19 and the contribution of brain tissue damage by SARS-CoV-2 to the morbidity and mortality of COVID-19 in older adults.     Drug discovery research and development of novel drugs, as well as re-purposing and repositioning existing drugs, for preventing and treating PASC in older adults, particularly drugs specific for COVID-19 related CNS targets and CNS mechanisms driving the viral-mediated pathophysiology, and research on blood-brain-barrier penetrant drug candidates to treat potential SARS-CoV-2 reservoirs in the CNS.
• Research to develop novel models for investigating concurrent aging and neurodegenerative processes in the context of SARS-CoV-2 infection.

Applications Not Responsive to this FOA: 

Applications proposing the following will be considered non-responsive to this FOA and will not be reviewed:

• Development of a therapeutic intervention.
• Testing the safety of an intervention and/or demonstrating pharmacodynamic or neurodynamic effects to establish dosing.
• Demonstrating efficacy or effectiveness of an intervention.
• Exclusively qualitative research.
• Correlation of patient-reported symptoms and/or neuropsychological testing and neuroimaging that do not carry the potential to identify pathways for the development of treatments.
• Research targeting post-intensive care syndrome in which it is hard to distinguish what is due to PASC and what is due to critical illness.
• Research on SARS-CoV-2 virus and PASC unrelated to changes in mental and/or neurological health.
• Research focused solely on the acute phase of SARS-CoV-2 infection with no implications to PASC.
• Research of other virus or pathogens with no implications to SARS-CoV-2 infection or PASC.

TBD

Public/State Controlled Institution of Higher Education
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. 

Please direct all inquiries to:

Lumy Sawaki-Adams, MD, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-827-1457
Email: lumy.sawaki-adams@nih.gov

Barbara Karp, MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 240-461-5127
Email: karpb@ninds.nih.gov

Collene Lawhorn, PhD
National Institute of Mental Health (NIMH)
Telephone: 301-451-4262
Email: collene.lawhorn@nih.gov

Luci Roberts, PhD
National Institute of Aging (NIA)
Telephone: 301-496-9350
Email: roberlu@mail.nih.gov