Effect of 2-HOBA in Persistent Immune Activation in Long COVID POTS

Inclusion criteria

• All participants should meet diagnostic criteria for Long COVID and POTS and as outlined below: Long COVID (LC) is defined by a range of symptoms affecting multiple organs that persist for more than three months following an acute SARS-CoV-2 infection. POTS: the presence of chronic symptoms lasting more than 3 months, along with orthostatic tachycardia (a HR increase over 30 bpm upon standing or exceeding 120 bpm without orthostatic hypotension) within 10 minutes upon standing or 75-degree head up tilt. For patients aged 18 and 21, an increase of more than 40 bpm or a standing HR over 130 bpm will be required for inclusion in the study. 2 Patients need confirmation of POTS diagnosis based on orthostatic vital signs obtained prior to enrollment in the study. SARS-CoV-2 infection 3 or more months prior identified by the follow signs: A. Meets the clinical OR epidemiological criteria.
• Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia.
• Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presents with acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization); or C. Presents with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test. D. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or E. Meeting clinical criteria AND/OR epidemiological criteria (See A). With a positive professional use or self-test, SARS-CoV-2 Antigen-Rapid Diagnostic Test. F. Documented by health care provider in clinical note or encounter.

Exclusion criteria

• Known active acute SARS-Cov-2 infection (4 weeks from onset)
• Moderate or severe immunocompromised patients,
• Known history of cardiovascular disease (atrioventricular block (AV block), myocardial infarction, angina, heart failure, pacemaker, stroke, transient ischemic attack within 6 months before enrollment),
• Uncontrolled hypertension (BP\>140/90 despite appropriate treatment);
• Type 1 or type 2 diabetes mellitus;
• Impaired hepatic function (AST or ALT greater than 1.5x the upper limit of normal or with total bilirubin ≥1.5mg/dl),
• Impaired renal function test (eGFR\<60 mL/min/1.73m2),
• Anemia (hemoglobin \<10 g/dl),
• Pregnant or breastfeeding women,
• Known history of autoimmune disease, steroid use or other immunotherapies,
• Inability to provide informed consent. We will also exclude individuals with known allergy sensitivity to components of the study medication, known contraindication to the study interventions, use of central acetylcholinesterase inhibitors (e.g., pyridostigmine, donezepil), aspirin allergy because salicylic acid is a metabolite of 2-HOBA; use of monoamine oxidase inhibitors (MAO-I) because of some inhibition of MAO-A is present in the anticipated therapeutic range of 2-HOBA. \-