RECOVER-AUTONOMIC Platform Protocol

The hypothesis is that some of the autonomic dysfunction symptoms are immune-mediated, so immunotherapy and other applicable therapies will result in improvement in autonomic symptoms.

Interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix.

Inclusion criteria

• ≥ 18 years of age at the time of enrollment
• Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization12ɸ ɸ Enrollment of participants with suspected or probable SARS-CoV-2 infection will only be allowed if they occurred before May 1, 2021 and be limited to no more than 10% of the total sample size per Study Drug Appendix. Refer to the Manual of Procedures (MOP) for details.

Suspected case of SARS-CoV-2 infection - Three options, A through C:

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.

Probable case of SARS-CoV-2 infection, defined as meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.

Confirmed case of SARS-CoV-2 infection - Two options, A through B:

A. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

• Moderate, self-identified autonomic symptoms (defined as COMPASS-31 >20) following a SARS-CoV-2 infection that has persisted for at least 12 weeks and is still present at the time of consent
• OHQ/OIQ, question 1 score >2

Exclusion criteria

• Known pregnancy, breast-feeding, or contemplating pregnancy during the study period
• Known active acute SARS-CoV-2 infection ≤ 4 weeks from enrollment
• Known renal failure (eGFR <20ml/1.73 m²)
• Known atrial fibrillation or significant cardiac arrhythmia
• Known cardiovascular conditions such as heart failure (Class 3-4), severe valvular disease
• Clinically significant atherosclerotic disease, defined as history of stroke or myocardial infarction or revascularization 6 months prior to enrollment and/or current symptomatic angina
• Existing uncontrolled hypertension
• Inability to comply with the protocol
• Any condition that the investigator believes makes it inappropriate to treat with study intervention, including severe debility.
• History of POTS or significant dysautonomia before COVID-19 index infection
• Enrolled in another clinical trial or another study intervention appendix in this platform protocol * Patients who are a part of observational studies (e.g. imaging) may be included in this trial. Participants may enroll in another interventional trial or re-enroll in this trial for a different study intervention appendix 30 days after end of study (Follow-up visit).