Purpose

The term post-acute COVID-19 syndrome or Long COVID is a disabling syndrome that persists beyond the 3-month convalescence period after COVID-19 infections. This syndrome affects mostly women (~80%), present with chronic tachycardia and Orthostatic intolerance symptoms without any identifiable cause. In addition, non-specific symptoms such as fatigue, headache, and "brain fog", commonly described in POTS patients are also present in this novel condition, recently named post-COVID-19 tachycardia syndrome, POTS variant. Reduced Vagal activity and unresolved inflammation is post-COVID-19 POTS is hypothesized as the cause of Long COVID

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Prior RT-PCR-confirmed COVID-19 infection. - Post-COVID-19 POTS will be defined as the presence of orthostatic tachycardia (>30 bpm) and chronic (>3 months) pre-syncopal symptoms.

Exclusion Criteria

  • Heart Disease: Myocardial Infarction, angina, heart failure - History of stroke, or transient ischemic attack - Undergone an invasive procedure for CVD (coronary artery bypass graft, angioplasty, valve replacement, pacemaker placement or other vascular surgeries) - Uncontrolled hypertension defined as persistent blood pressure >140/90. - Post-menopausal women. - Diabetes Mellitus Type 1 or Type 2. , - Impaired Hepatic function - Impaired renal function test (eGFR<60 mL/min/1.73m2). - Ongoing substance abuse. - Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study. - History of seizures. - Chronic use of steroids, NSAIDs. - On biologics such as anti-IL6 (omalizumab) and anti-TNF-alpha drugs - Pregnancy or breastfeeding

Study Design

Phase
N/A
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
Case-control study
Primary Purpose
Diagnostic
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
PNS Activity Measurement in relation to the Inflammation in post- COVID 19 POTS
PNS activity Measurement Biochemical endpoints: Blood sample for Inflammatory markers. Autonomic symptoms assessment questionnaire (COMPASS-31),32 quality of life EQ-5D and neuropsychological tests
  • Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients
    Blood samples: For peripheral blood mononuclear cells (PBMCs) isolation, cytokines, CITE-Seq studies, plasma catecholamines and acetylcholine.
  • Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation)
    Hemodynamic data will be processed in PV-Wave language (PV-wave, Visual Numerics Inc. Houston, TX). Detected beat-to-beat values of R-R intervals (RRI) and BP will be interpolated using a low-pass filtered (cutoff 2 Hz). Data segments will be used 180 seconds for spectral analysis. Linear trends will be removed, and power spectral density will be estimated with the FFT-based Welch algorithm. The total power (TP) and the power in the low (LF: 0.04 to <0.15 Hz), and high (HF: 0.15 to < 0.40 Hz) frequency ranges will be calculated to estimate PNS modulation of heart rate (HF-RRI) and sympathetic modulation of blood pressure (LF-SBP).
  • Diagnostic Test: Autonomic Symptoms assessment
    An autonomic symptoms assessment questionnaire (COMPASS-31),32 quality of life EQ-5D and neuropsychological tests

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Cyndya Shibao, MD, MSCI
cyndya.shibao@vumc.org

More Details

Status
Recruiting
Sponsor
Vanderbilt University Medical Center

Study Contact

Cyndya Shibao, M.D.
615-936-4584
cyndya.shibao@vumc.org

Detailed Description

Post-acute sequelae of COVID-19 infection or Long COVID is a growing concern, even in patients with mild initial illness. These patients develop numerous chronic debilitating symptoms including fatigue, chest pain, reduced exercise tolerance and tachycardia, with symptoms persisting weeks beyond the initial infection. Preliminary data shows that post-COVID-19 POTS patients have reduced parasympathetic (PNS) function. Given that the PNS protects against inflammation, it is hypothesize that post-COVID-19 POTS is caused by reduced PNS activity, which in turn, contributes to persistent inflammation, orthostatic intolerance and OI symptoms Aim of the study is to test the hypothesis that reduced PNS activity is associated with persistent inflammation in patients with post-COVID-19 POTS. Primary Outcome Measures: To 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. The primary endpoint is IL-6 levels. Rationale: Elevated levels of IL-6, CRP and D-dimer are found in Long COVID patients, which resembles post-COVID tachycardia syndrome in POTS patients. Notably, stimulation of the efferent Vagus nerve has been shown to reduce cytokine production and systemic inflammation in response to endotoxin. Hence, decreased PNS function, as reported with acute SARS-CoV-2 infection and in post-COVID-19 POTS patients, may render these patients prone to persistent inflammation. The study aims to determine the link between PNS activity and immune activation in post-COVID-19 POTS. Study population: Total of 60 participants, 30 post-COVID-19 POTS patients and 30 controls with history of COVID-19 infection without sequelae. Study Visits: 3 visits, 2 in person and 1 telemedicine, Study procedures include EKG, urine and blood sample collection, Orthostatic Standing Test, Measurement of blood volume using carbon monoxide rebreathing technique, Tilt table test. Participants will be asked to complete an autonomic symptoms assessment questionnaire (COMPASS-31),32 quality of life EQ-5D and neuropsychological tests. Data and Safety Monitoring Plan: The Data and Safety Monitoring Officer (DSMO) will provide objective review of treatment results as they relate to human safety and data quality. Dr. Cheryl Laffer, Professor of Medicine, Division of Clinical Pharmacology will serve as DSMO. The DSMO will review the initial protocol and will receive reports of the progress of the study every 12 months. These reports will provide information regarding recruiting, safety reporting, data quality, and efficacy. Statistical Considerations: Biostatistical Section Power analysis: The primary endpoint is serum IL-6. The proposed sample size of 60 (30 pairs of patients and controls) provides 90% power to detect an effect size of 0.62 for the mean difference in IL-6 between post-COVID-19 POTS (cases) and controls (COVID-19 infected w/o sequelae), with the two-sided type I error = 5%. This calculation is based on the preliminary data of mean difference of IL-6 ≈ 1.82 and the SD ≈ 2.94 in POTS.6 The effect size is defined as the ratio of mean IL-6 difference between cases and controls to standard deviation. Data analysis plan: Demographic information will be tabulated. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percent and frequencies for categorical parameters, will be presented. T-test or Mann-Whitney (as appropriate) will be applied to examine the mean differences between cases and controls with respect to the outcomes. The conditional logistic regression model will be applied for the multivariable data analysis. The adjusted p-values and the adjusted 95% confidence intervals (CIs) will be reported.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.