An Observational Study of Neurologic Function After COVID-19 Infection

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, and many of these symptoms are neurologic. 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 SARSCoV-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. 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. If there are abnormalities noted on the baseline study procedures, participants may return for a repeat of some study procedures within 12 months from completion of their baseline study visit. Objectives: Primary Objective: To investigate structural abnormalities by brain MRI in those with prior SARS-CoV-2 infection and persistent neurologic symptoms. Secondary objective: To investigate other components of neurologic function in those with prior SARS-CoV-2 infection and 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: 1. Neurologic examination: The number and character of abnormalities associated with both central and peripheral nervous system disease. 2. Autonomic testing: The number and character of test results indicating autonomic nervous system or catecholaminergic dysfunctions as evidenced by abnormal physiological and neurochemical measures at rest or in responses to the Valsalva maneuver or head-up tilting. Study Population: This study will enroll 50 participants. Description of Sites/Facilities Enrolling Participants: The NIH Clinical Center will be the site of all research studies done under this protocol. Study Duration: We anticipate that this study will begin enrollment September 2020 and will complete data analysis by December 2022. Participant Duration: Participants will complete all required study procedures within an approximately two-week time frame. Participants may return for optional follow up with a repeat of some study procedures and those participants will complete the study at that point.

- INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Stated willingness to comply with all study procedures and availability for the duration of the study 2. Male or female, aged at least 18 years at the time of enrollment 3. Enrolled in the screening phase of Protocol 000089 Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health 4. Positive COVID-19 test result at least six weeks prior to enrollment and exhibiting persistent neurologic symptoms evidenced by a positive response to at least one of the following: 1. Do you have ongoing issues with being lightheaded or dizzy and if so, are these issues made worse when you sit or stand up quickly? 2. Do you have ongoing issues with gait instability, problems with vision, speech, swallowing? 3. Do you have ongoing issues with sensation or strength in your face/arms/legs? 5. Ability of subject to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Presence of a contraindication to research MRI brain 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 dose oral benzodiazepine. 2. 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. 3. Contraindication to autonomic testing, including refractory ventricular arrhythmias or symptomatic coronary artery disease. 4. 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 Hypotension Syndrome), as determined by the study investigators. 5. Fever or respiratory symptoms in the last seven days.

Study Location