Immune Profiling for Post-COVID Syndrome

Overseen By Cyndya Shibao, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: Steroids, NSAIDs, Immunosuppressants, others

Disqualifiers: Heart disease, Stroke, Immune treatments, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as steroids, anti-IL6, anti-TNF-alpha, other immunosuppressants, and NSAIDs (non-steroidal anti-inflammatory drugs) at least one week before blood sampling. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the treatment Compass 31, Autonomic Symptoms Assessment Questionnaire for Post-COVID Syndrome?

The research indicates that the COMPASS-31 questionnaire is a useful tool for assessing autonomic symptoms in post-COVID patients, which can help identify those who may benefit from early rehabilitative and pharmacological therapy to prevent long-term autonomic issues. ^{1 2 3 4 5}

Is the treatment for post-COVID syndrome safe for humans?

The studies primarily focus on assessing symptoms and conditions related to post-COVID syndrome, such as autonomic dysfunction and fatigue, rather than evaluating the safety of a specific treatment. Therefore, there is no direct safety data available for the treatment in question. ^{1 2 4 6 7}

How is the Compass 31 treatment different from other treatments for post-COVID syndrome?

Compass 31 is unique because it is a questionnaire used to assess autonomic symptoms, rather than a traditional drug or therapy. It helps identify and monitor autonomic dysfunction in long COVID patients, which is a key feature of the condition. ^{1 4 8 9 10}

What is the purpose of this trial?

Parasympathetic nervous system (PNS) is part of the body's autonomic nervous system(PNS) protects body against inflammation. Study shows that reduced PNS function activity is associated with persistent inflammation. Preliminary data from the studies shows, that post-COVID-19 POTS patients have reduced parasympathetic (PNS) function. Given that the PNS protects against inflammation, this clinical trial aims to prove that post-COVID-19 POTS is caused by reduced PNS activity, which in turn, contributes to persistent inflammation, orthostatic intolerance, and OI symptoms. The study will evaluate immune cell activation in post-COVID-19 POTS and patients with history of COVID-19 infection without sequelae and correlate this with the degree of decreased PNS activity.

Eligibility Criteria

This trial is for adults with a confirmed history of COVID-19 who now have symptoms like rapid heartbeat and dizziness when standing, known as POTS. These symptoms must have started within two months after COVID infection and lasted more than three months.

Inclusion Criteria

I have had a confirmed case of COVID-19.

I have had fast heart rate and dizziness for over 3 months after getting COVID-19.

I have been diagnosed with POTS and experience rapid heartbeat and near-fainting for over 3 months.

Exclusion Criteria

I have received treatments like plasmapheresis or IVIG.

I regularly use steroids or immunosuppressants like anti-IL6 or anti-TNF-alpha.

I have a history of heart issues or surgeries related to cardiovascular disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study Visit

Participants undergo assessments including autonomic symptoms assessment, quality of life evaluation, and blood sample collection

1 day

1 visit (in-person)

Data Analysis

Data analysis including demographic information tabulation and statistical tests on collected data

4-8 weeks

Follow-up

Participants are monitored for any changes in autonomic symptoms and inflammatory markers

4 weeks

Treatment Details

Interventions

• Compass 31

Trial Overview The study tests if reduced function of the part of the nervous system that calms inflammation (PNS) leads to long-term symptoms in post-COVID patients. It involves measuring immune cell activation and comparing it with PNS activity levels.

Participant Groups

Group I: Post- COVID 19 POTS patients with Controls Experimental Treatment 3 Interventions

Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31):Gender, age, and BMI-matched: Controls are :COVID-19 infected without sequelae

Group II: Post- COVID 19 POTS patients Experimental Treatment 3 Interventions

Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31): In post-COVID-19 POTS (cases).

Group III: POTS patients Experimental Treatment 3 Interventions

Inflammatory markers IL-6,Cytokines (IL-17, and IFN-ɣ), Autonomic symptoms assessment questionnaire (COMPASS 31):Gender, age, and BMI-matched: patients with diagnosis of POTS

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Findings from Research

A study of 112 patients recovering from COVID-19 showed that while autonomic symptoms and quality of life initially improved after discharge, many patients experienced a worsening of symptoms at 6 and 12 months, indicating a significant risk for Long-COVID autonomic syndrome.

The findings suggest that early rehabilitative and pharmacological interventions are crucial for patients shortly after infection to help prevent the development of long-term autonomic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long-COVID autonomic syndrome in hospitalized patients: A one-year prospective cohort study. Rigo, S., Barbic, F., Khalaf, K., et al.[2023]

In a study of 180 post-COVID patients, 13.8% exhibited orthostatic hypotension, highlighting that autonomic nervous system dysfunction can be a common complication after COVID-19.

The COMPASS-31 questionnaire revealed significant dysautonomic symptoms, particularly in orthostatic intolerance, with higher scores in patients with neurological complaints, indicating the need for ongoing monitoring of autonomic symptoms in post-COVID care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic dysfunction in post-COVID patients with and witfhout neurological symptoms: a prospective multidomain observational study. Buoite Stella, A., Furlanis, G., Frezza, NA., et al.[2022]

In a study of 27 patients with post-COVID-19 syndrome, a majority exhibited symptoms of autonomic dysfunction, particularly orthostatic intolerance, which occurred without significant changes in blood pressure or heart rate.

The findings suggest a potential causal relationship between COVID-19 infection and the development of autonomic symptoms, although the study cannot definitively prove causation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autonomic dysfunction following COVID-19 infection: an early experience. Shouman, K., Vanichkachorn, G., Cheshire, WP., et al.[2023]

In a study of 39 participants, those with long COVID-19 and fatigue showed significant autonomic dysregulation, as indicated by changes in the NOL index, compared to control participants without COVID-19.

The findings suggest that dysautonomia may be a key factor in the persistent symptoms experienced by long COVID-19 patients, such as fatigue and hypoxia, highlighting the need for further investigation into autonomic nervous system involvement in long COVID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical characterization of dysautonomia in long COVID-19 patients. Barizien, N., Le Guen, M., Russel, S., et al.[2022]

In a study of 184 post-COVID-19 patients, most reported over 10 symptoms, with fatigue (84.9%) and decreased physical capacity (83.0%) being the most common, highlighting the significant symptom burden associated with post-COVID-19 syndrome (PCS).

Clinical assessments revealed abnormalities in fatigue, cognition, and lung function, indicating that ongoing monitoring and interdisciplinary care are crucial for managing PCS symptoms, which often persist and evolve over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Clinical Features of Post-COVID-19 Patients-Symptoms, Fatigue and Physical Function at 3- and 6-Month Follow-Up. Steinmetz, A., Gross, S., Lehnert, K., et al.[2023]

In a study of 76 individuals diagnosed with ME/CFS, significant immunological abnormalities were found in all patients, indicating a potential underlying immune dysfunction in this condition.

The study also revealed that 75% of individuals with post-COVID ME/CFS exhibited postural orthostatic tachycardia, which was significantly higher than in healthy controls, suggesting a distinct cardiovascular response associated with this syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground? Ryabkova, VA., Gavrilova, NY., Fedotkina, TV., et al.[2023]

In a study of 176 convalescent COVID-19 patients, fatigue was a common symptom reported regardless of the initial severity of their COVID-19 illness, indicating that all patients are at risk for post-acute sequelae of COVID-19 (PASC).

The research found a significant correlation between the severity of fatigue and the levels of CD3+CD4+ T cells in the blood, suggesting that these T cells may play a role in the development of fatigue after COVID-19 and could potentially serve as a biomarker for assessing PASC severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19. Pink, I., Hennigs, JK., Ruhl, L., et al.[2023]

A study involving 275 individuals revealed significant differences in immune cell populations and exaggerated antibody responses in those with long COVID compared to controls, suggesting altered immune function may contribute to long COVID symptoms.

Machine learning analysis of immune data identified key biological features associated with long COVID, which could aid in understanding its pathobiology and developing potential biomarkers for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinguishing features of long COVID identified through immune profiling. Klein, J., Wood, J., Jaycox, JR., et al.[2023]

In a study of 215 individuals with Long COVID, significant differences in immune cell populations and elevated antibody responses against both SARS-CoV-2 and other viruses, like Epstein-Barr, were identified, suggesting a complex immune response in these patients.

Lower cortisol levels were consistently observed in individuals with Long COVID, making it a key predictor for distinguishing this condition, which could help in developing objective biomarkers for diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinguishing features of Long COVID identified through immune profiling. Klein, J., Wood, J., Jaycox, J., et al.[2023]

Long COVID can lead to cardiovascular autonomic imbalances, known as dysautonomia, which may be linked to underlying mechanisms such as neurotropism and autoimmune dysfunction, affecting patients for more than 4 weeks after initial infection.

Heart rate variability is a useful, non-invasive method to assess these autonomic imbalances in Long COVID patients, indicating potential risks for long-term cardiovascular issues and highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers. Marques, KC., Quaresma, JAS., Falcão, LFM.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The Long-COVID autonomic syndrome in hospitalized patients: A one-year prospective cohort study. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Autonomic dysfunction in post-COVID patients with and witfhout neurological symptoms: a prospective multidomain observational study. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Autonomic dysfunction following COVID-19 infection: an early experience. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Clinical characterization of dysautonomia in long COVID-19 patients. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Longitudinal Clinical Features of Post-COVID-19 Patients-Symptoms, Fatigue and Physical Function at 3- and 6-Month Follow-Up. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-COVID Syndrome: A Common Neuroimmune Ground? [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Distinguishing features of long COVID identified through immune profiling. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Distinguishing features of Long COVID identified through immune profiling. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers. [2023]