COVID-19NCT04564287
An Observational Study of Neurologic Function After COVID-19 Infection
An observational study of COVID-19, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: COVID-19 is an infection caused by a coronavirus. It can affect different parts of the body. For most people, it causes fevers or trouble breathing. Some people can have symptoms long after they recover. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2020to 12 Apr 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Community Sample
Who may be able to join
- In order to be eligible to participate in the PASC cohort, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged at least 18 years at the time of enrollment
- Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
- Positive COVID-19 test result (per the methodology used for inclusion in Protocol 000089) at least six weeks prior to enrollment and exhibiting persistent neurologic symptoms evidenced by a positive response to at least one of the following:
- Do you have ongoing issues with being lightheaded or dizzy and if so, are these issues made worse when you sit or stand up
Show all 17Show fewer
- quickly?
- Do you have ongoing issues with gait instability, problems with vision, speech, swallowing?
- Do you have ongoing issues with sensation or strength in your face/arms/legs?
- Ability of subject to understand and the willingness to sign a written informed consent document.
- In order to be eligible to participate in the Fully Recovered cohort, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged at least 18 years at the time of enrollment
- Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
- Positive COVID-19 test result (per the methodology used for inclusion in Protocol 000089) in at least six weeks prior to enrollment.
- A self-reported illness narrative of recovery to prior health after a SARS/CoV2 infection, without residual fatigue, brain fog, orthostatic intolerance, or exercise intolerance.
- Ability of subject to understand and the willingness to sign a written informed consent document.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Presence of a contraindication to research MRI with gadolinium, including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR <45 mmol/L, pregnancy or lactation, or claustrophobia that is unable to be adequately treated with a low oral dose of a benzodiazepine.
- Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets < 50,000/microL, PT or PTT >1.5 x ULN for the NIH Clinical Center, or otherwise inability to complete the procedure.
- Contraindication to autonomic testing, including refractory ventricular arrhythmias or symptomatic coronary artery disease.
- A condition prior to the diagnosis of COVID-19 infection that would significantly confound interpretation of the research tests (e.g., prior diagnosis of postural orthostatic tachycardia syndrome), as determined by the study investigators.
- Fever or respiratory symptoms in the last seven days.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: An Observational Study of Neurologic Function After COVID -19 Infection
Background:
COVID-19 is an infection caused by a coronavirus. It can affect different parts of the body. For most people, it causes fevers or trouble breathing. Some people can have symptoms long after they recover. Researchers want to learn if there are signs of changes in the nervous system that may be related to COVID-19.
Read more
Objective:
To test the nervous system (the brain and nerves) in people who have had COVID-19 yet still have certain symptoms even after recovering.
Eligibility:
People age 18 and older who had COVID-19 and still have neurologic symptoms after they recovered from the initial infection.
Design:
Participants will be screened with a medical record review.
Participants will have a neurological exam. They will complete pen-and-paper tests of their memory and thinking. They will complete a smell test with 'scratch-and-sniff' booklets.
They will give blood samples.
Participants will have magnetic resonance imaging (MRI) of the brain. Soft padding or a coil will be placed around their head. They will lie on a table that slides in and out of the MRI scanner. They will get a contrast dye through an intravenous (IV) catheter.
Participants blood pressure, blood flow, skin temperature, sweating, and breathing will be monitored.
Participants will have an electrocardiogram to measure heart function.
Participants will blow into a mouthpiece for several seconds.
Participants will lie on a table that has a motor. The motor tilts the table. Participants will have blood drawn through an IV as the table tilts.
Participants will have a lumbar puncture. A small needle will be inserted into the spinal canal to obtain fluid.
Participants may repeat some tests 8 weeks to 1 year later.
Read the detailed description
Study Description:
This study will characterize ongoing neurologic abnormalities in those who recovered from acute COVID-19 infection yet have persistent neurologic symptoms. Despite clinical recovery from the acute infection, some individuals continue to experience ongoing symptoms, at times several months after recovery (Post-Acute Sequelae of SARS CoV-2 Infection, PASC), and many of these symptoms are neurologic (neuro-PASC). The NIH Clinical Center provides the breadth of expertise and resources to best investigate this patient group. This study will collect a broad array of specialized neurologic testing in this group who, despite recovering from the acute SARS-CoV-2 infection, continue to experience neurological symptoms. It is hypothesized that this group will have abnormalities on neurologic testing that may identify discrete phenotypes of COVID-19 sequelae. Additionally, by including a group of individuals who have fully recovered without residual neurological symptoms, this study should be able to determine if there are abnormal results of study procedures in the absence of symptoms.
Pre-screening for this study will be done under the study, Post-Coronavirus Disease 19 Syndrome at the National Institutes of Health. Potentially eligible participants will be identified under the screening arm of that study and will be referred to the study team. If deemed eligible for this study based on a review of available records and a telephone discussion with the potential participant, participants may enroll. Enrollment will include a visit to the NIH Clinical Center for informed consent and completion of the study procedures. We anticipate that the baseline study procedures will take approximately 2-3 outpatient visits to complete or the participant may be admitted as an inpatient. Participants may return for an optional follow-up visit (with a repeat of the study procedures done initially) after at least 6 months from completion of their baseline study visit testing.
Objectives:
Primary Objective: To investigate structural brain MRI in those with prior SARS-CoV-2 infection and persistent neurologic symptoms and in those with prior SARS-CoV-2 infection without persistent neurologic symptoms.
Secondary objective:To investigate other components of neurologic function in those with prior SARS-CoV-2 infection and persistent neurologic symptoms and in those with prior SARS-CoV-2 infection and without persistent neurologic symptoms.
Endpoints:
Primary endpoint: The number and character of brain MRI abnormalities on a dedicated research MRI protocol optimized to detect COVID-19-associated disease.
Secondary endpoints:
- Neurologic examination: The number and character of abnormalities associated with both central and peripheral nervous system disease.
- Autonomic testing: The number and character of test results indicating autonomic nervous system or catecholaminergic dysfunctions as evidenced by abnormal physiological or neurochemical measures at rest or in response to the Valsalva maneuver or head-up tilting.
- Conditions
- COVID-19
- Keywords
- Neurological, COVID-19, Coronavirus, Autonomic, Brain, Natural History
- Medical subject headings
- COVID-19, Neurologic Manifestations, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Fully Recovered Individuals | Individuals with history of Covid-19 infection who have fully recovered without residual neurological symptoms | |
| Patients with neuro-PASC | Patients with history of Covid-19 infection and persistent neurological symptoms (Post-Acute Sequelae of SARS CoV-2 Infection, neuro-PASC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI brain
The number and character of brain MRI abnormalities on a dedicated research MRI protocol optimized to detect Covid-19-associated disease.
Measured: NIH Clinical Center Visit
Secondary outcomes (2)
Neurological Examination
Neurologic examination: The number and character of abnormalities associated with both central and peripheral nervous system disease.
Measured: NIH Clinical Center Visit
Autonomic Testing
Autonomic testing: The number and character of test results indicating autonomic nervous system disease as evidenced by abnormal heart rate and blood pressure responses during tilt table testing.
Measured: NIH Clinical Center Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start28 Oct 2020
- Primary completion12 Apr 2023
- Study completion12 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Avindra Nath, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04564287
- Sponsor's protocol ID
- 10000094
- Other IDs
- 000094-N
- Status last verified
- Nov 2025
- First submitted
- 24 Sep 2020
- Last updated
- 1 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study of Neurologic Function After COVID -19 Infection
- ClinicalTrials.gov ID
- NCT04564287
- Acronym / sponsor ID
- 10000094
- Conditions
- COVID-19
- Keywords
- Neurological, COVID-19, Coronavirus, Autonomic, Brain, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 12 Apr 2023 (actual)
- Study completion
- 12 Apr 2023 (actual)
- First posted
- 25 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
COVID-19 is an infection caused by a coronavirus. It can affect different parts of the body. For most people, it causes fevers or trouble breathing. Some people can have symptoms long after they recover. Researchers want to learn if there are signs of changes in the nervous system that may be related to COVID-19.
Objective:
To test the nervous system (the brain and nerves) in people who have had COVID-19 yet still have certain symptoms even after recovering.
Eligibility:
People age 18 and older who had COVID-19 and still have neurologic symptoms after they recovered from the initial infection.
Design:
Participants will be screened with a medical record review.
Participants will have a neurological exam. They will complete pen-and-paper tests of their memory and thinking. They will complete a smell test with 'scratch-and-sniff' booklets.
They will give blood samples.
Participants will have magnetic resonance imaging (MRI) of the brain. Soft padding or a coil will be placed around their head. They will lie on a table that slides in and out of the MRI scanner. They will get a contrast dye through an intravenous (IV) catheter.
Participants blood pressure, blood flow, skin temperature, sweating, and breathing will be monitored.
Participants will have an electrocardiogram to measure heart function.
Participants will blow into a mouthpiece for several seconds.
Participants will lie on a table that has a motor. The motor tilts the table. Participants will have blood drawn through an IV as the table tilts.
Participants will have a lumbar puncture. A small needle will be inserted into the spinal canal to obtain fluid.
Participants may repeat some tests 8 weeks to 1 year later.
Detailed description
Study Description:
This study will characterize ongoing neurologic abnormalities in those who recovered from acute COVID-19 infection yet have persistent neurologic symptoms. Despite clinical recovery from the acute infection, some individuals continue to experience ongoing symptoms, at times several months after recovery (Post-Acute Sequelae of SARS CoV-2 Infection, PASC), and many of these symptoms are neurologic (neuro-PASC). The NIH Clinical Center provides the breadth of expertise and resources to best investigate this patient group. This study will collect a broad array of specialized neurologic testing in this group who, despite recovering from the acute SARS-CoV-2 infection, continue to experience neurological symptoms. It is hypothesized that this group will have abnormalities on neurologic testing that may identify discrete phenotypes of COVID-19 sequelae. Additionally, by including a group of individuals who have fully recovered without residual neurological symptoms, this study should be able to determine if there are abnormal results of study procedures in the absence of symptoms.
Pre-screening for this study will be done under the study, Post-Coronavirus Disease 19 Syndrome at the National Institutes of Health. Potentially eligible participants will be identified under the screening arm of that study and will be referred to the study team. If deemed eligible for this study based on a review of available records and a telephone discussion with the potential participant, participants may enroll. Enrollment will include a visit to the NIH Clinical Center for informed consent and completion of the study procedures. We anticipate that the baseline study procedures will take approximately 2-3 outpatient visits to complete or the participant may be admitted as an inpatient. Participants may return for an optional follow-up visit (with a repeat of the study procedures done initially) after at least 6 months from completion of their baseline study visit testing.
Objectives:
Primary Objective: To investigate structural brain MRI in those with prior SARS-CoV-2 infection and persistent neurologic symptoms and in those with prior SARS-CoV-2 infection without persistent neurologic symptoms.
Secondary objective:To investigate other components of neurologic function in those with prior SARS-CoV-2 infection and persistent neurologic symptoms and in those with prior SARS-CoV-2 infection and without persistent neurologic symptoms.
Endpoints:
Primary endpoint: The number and character of brain MRI abnormalities on a dedicated research MRI protocol optimized to detect COVID-19-associated disease.
Secondary endpoints:
- Neurologic examination: The number and character of abnormalities associated with both central and peripheral nervous system disease.
- Autonomic testing: The number and character of test results indicating autonomic nervous system or catecholaminergic dysfunctions as evidenced by abnormal physiological or neurochemical measures at rest or in response to the Valsalva maneuver or head-up tilting.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fully Recovered Individuals | – | –Individuals with history of Covid-19 infection who have fully recovered without residual neurological symptoms |
| Patients with neuro-PASC | – | –Patients with history of Covid-19 infection and persistent neurological symptoms (Post-Acute Sequelae of SARS CoV-2 Infection, neuro-PASC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Community Sample
Key inclusion criteria (17 listed)
- In order to be eligible to participate in the PASC cohort, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged at least 18 years at the time of enrollment
- Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
- Positive COVID-19 test result (per the methodology used for inclusion in Protocol 000089) at least six weeks prior to enrollment and exhibiting persistent neurologic symptoms evidenced by a positive response to at least one of the following:
Key exclusion criteria (6 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Presence of a contraindication to research MRI with gadolinium, including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR <45 mmol/L, pregnancy or lactation, or claustrophobia that is unable to be adequately treated with a low oral dose of a benzodiazepine.
- Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets < 50,000/microL, PT or PTT >1.5 x ULN for the NIH Clinical Center, or otherwise inability to complete the procedure.
- Contraindication to autonomic testing, including refractory ventricular arrhythmias or symptomatic coronary artery disease.
- A condition prior to the diagnosis of COVID-19 infection that would significantly confound interpretation of the research tests (e.g., prior diagnosis of postural orthostatic tachycardia syndrome), as determined by the study investigators.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
MRI brain
Time frame: NIH Clinical Center Visit
The number and character of brain MRI abnormalities on a dedicated research MRI protocol optimized to detect Covid-19-associated disease.
2 secondary outcomes
Neurological Examination
Time frame: NIH Clinical Center Visit
Autonomic Testing
Time frame: NIH Clinical Center Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Avindra Nath, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI brain (time frame: NIH Clinical Center Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.