Post-Viral Syndromes

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

Objective: The primary objective is to explore the clinical and biological phenotypes of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) and post-acute sequelae of COVID-19 (PASC). The secondary objective is to explore the pathophysiology of fatigue and post-exertional malaise (PEM). Study population: Up to 1890 persons will be enrolled as part of the protocols. For ME/CFS, up to 150 persons aged 18-60 will be part of 3 study groups: 50 ME/CFS patients whose fatigue began after an infection, 50 non-fatigued participants with a documented history of Lyme disease exposure and treatment, and 50 healthy volunteers. The study has a target of completing all study procedures on 20 enrolled participants in each group. Up to an additional 176 persons reporting a community diagnosis of ME/CFS will be enrolled into focus groups to discuss the experience of post-exertional malaise. Up to an additional 10 healthy volunteers and 10 ME/CFS patients may be enrolled to refine the protocols' electrophysiological and neuroimaging techniques. For PASC, up to 1540 persons 18 years of age or older will participate in a Survey study, in which telephone interviews and internet-based questionnaires will be collected for both descriptive research and participant screening purposes. From this group, up to 240 PASC patients and SARS-CoV-2 recovered volunteers will be enrolled in an inpatient evaluation visit. From this group, up to 110 PASC patients and SARS-CoV-2 recovered volunteers will be enrolled in an inpatient exercise stress visit. Design: This is a single-center, exploratory, cross-sectional study of PI-ME/CFS and PASC. Participants will have an initial visit, which will encompass 5 day long inpatient admission at the NIH Clinical Center. Case status for ME/CFS and PASC participants will be determined after the visit by a case adjudication process utilizing an expert physician committee and published guidelines. Adjudicated participants meeting inclusion criteria may be invited back to participate in an exercise stress visit, which will encompass a 5 day long inpatient admission. Detailed subjective and objective measurements and biological specimens will be serially collected before and up to 96 hours after a peak exercise test capable of inducing post-exertional malaise during this visit. All procedures will be completed on all three study groups to allow for optimal inter-group comparisons. Outcome Measures: The primary purpose of this protocol is to perform exploratory analysis of collected samples for the generation of new hypotheses regarding ME/CFS and PASC. The types of analyses to be performed will be wide ranging. Planned areas of focus include: 1. Characterization of the immune system and inflammatory signaling in collected samples at baseline and following maximal exercise exertion. 2. Characterization of the pattern of microbiome in collected samples at baseline and following maximal exercise exertion. 3. Characterization of bioenergetics, autonomic, and metabolic function in collected samples at baseline and following maximal exercise exertion. 4. Characterization of physical and cognitive fatigue using functional magnetic resonance imaging and transcranial magnetic stimulation at baseline and following maximal exercise exertion. 5. Characterization of neurocognition at baseline and following maximal exercise exertion. 6. Characterization of brain function and connectivity at baseline and following maximal exercise exertion. 7. Characterization of autonomic function at baseline and following maximal exercise exertion. 8. Characterization of gene expression profiles in collected samples at baseline and following maximal exercise exertion.