Repurposed Approved Therapies for Outpatient Treatment of Patients With Early-Onset COVID-19 and Mild Symptoms
Repurposed Approved Therapies for Outpatient Treatment of Patients With Early-Onset COVID-19 and Mild Symptoms
The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in
 certain subgroups of patients. To date, no treatment has been shown to be effective in
 patients with early-onset disease and mild symptoms. Experimental studies have demonstrated a
 potential anti-inflammatory role of Fluvoxamine, Metformin and Ivermectin in SARS-CoV-2
 infections and observational studies have suggested a reduced complications in patients with
 COVID-19 disease.
In December 2019 a series of viral pneumonia cases were reported in the city of Wuhan, China
 and a new subtype of coronavirus has been identified as the causative agent of this
 condition. On February 11, 2000 the disease has been characterized as COVID-19 and on March
 11 the World Health Organization (WHO) declared a state of worldwide pandemic. On January 25,
 2021 there are 98,794,942 cases and 2,124,193 documented deaths (global case-fatality ratio
 of 2.15%).

 To date, no early treatment has been identified as effective in combating this disease which
 has been identified as with high morbidity and mortality. Epidemiological data suggest that
 despite development of vaccines we will have hundreds od thousands of cases in the next two
 years.

 Thus, we propose the repositioning of three drugs which experimentally have shown
 anti-inflammatory activity against SARS-CoV2 and some clinical evidence derived from
 observational studies on reducing complications if used early on the disease, before
 inflammatory cascade is fully activated.
Inclusion Criteria:

 1. Patients over 18 years old with the ability to provide free and informed consent

 2. Acute Flu-Like symptoms < 07 days.

 3. All patient need to have at lease ONE enhancement factor:

 1. Age > 50 years;

 2. Diabetes mellitus requiring oral medication or insulin

 3. Systemic arterial hypertension requiring at least 01 oral medication for BP
 control;

 4. Known cardiovascular diseases (heart failure, congenital heart disease, valvar
 heart valve disease, coronary artery disease, cardiomyopathies)

 5. Symptomatic lung disease (emphysema, chronic bronchitis)

 6. Symptomatic asthma patients requiring chronic use of agents for control of
 symptoms.

 7. Smoking

 8. Obesity, defined as BMI> 30 kg / m2 body weight

 9. Transplanted patients

 10. Patient with stage IV chronic kidney disease or on dialysis.

 11. Immunosuppressed patients / using corticosteroid therapy (equivalent to at least
 10 mg of prednisone per day) and / or immunosuppressive therapy)

 12. Patients with a history of cancer in the last 05 years or undergoing treatment of
 a current cancer

 13. Chronic renal disease KDIGO IV or End-Stage Renal Disease on chronic ambulatory
 renal replacement therapy

 4. Patient with positive rapid test for SARS-CoV2 antigen performed on occasion of the
 screening or patient with a positive SARS-CoV2 diagnostic test within 07 days of the
 onset of symptoms.

 5. Willingness to use the proposed investigative treatment and follow the
 protocol-related procedures foreseen in the research

 Exclusion Criteria:

 1. Negative SARS-CoV2 test.

 2. Flu-like symptom onset 08 days or more.

 3. Patients with COVID-19 being referred for hospitalization;

 4. Patients with history of SARS-CoV-2 vaccine shot;

 5. Patients with acute respiratory conditions due to other causes;

 6. Dyspnea secondary to other acute and chronic respiratory causes or infections (eg:
 Decompensated COPD, acute bronchitis, pneumonia, primary pulmonary arterial
 hypertension)

 7. Acute Flu-Like condition presenting with at least ONE of the criteria below:

 1. Respiratory Rate> 28 / min;

 2. SaO2 <90% or <93% in nasal oxygen therapy at 10 l / min;

 3. PaO2 / FIO2 <300 mmHg

 8. Patients using serotonin reception inhibitors (Donepezil, Sertraline)

 9. Use of the following medications in the last 14 days:

 1. Monoamine Oxide Inhibitors (MAOIs): Phenelzine, Tranylcypromine, Selegiline,
 Isocarboxazide, moclobemide;

 2. Use of iodinated contrasts during start of treatment through D14;

 3. Use of antiretroviral agents

 10. Patients with severe psychiatric disorders or major uncontrolled depression or
 controlled with any of the prohibited drugs (see above);

 11. Pregnant or breastfeeding patients;

 12. History of severe ventricular cardiac arrhythmia (ventricular tachycardia, patients
 with ventricular fibrillation recovered) or Long QT Syndrome;

 13. History of diabetic ketoacidosis or clinical condition that maintains persistent
 acidosis

 14. Surgical procedure or use of contrast designed to occur during treatment or up to 04
 days after the last dose of the study medication;

 15. Current daily and / or uncontrolled alcoholism;

 16. History of seizures in the last month or uncontrolled medical condition;

 17. Clinical history of Liver Cirrhosis or Child-Pugh C classification;

 18. Patients with known severe degenerative neurological diseases and / or diseases
 serious mental disorders;

 19. Inability of the patient or representative to give consent or adhere to the procedures
 proposed in the protocol;

 20. Known hypersensitivity and / or intolerance to Fluvoxamine, Ivermectin or Metformin;

 21. Inability to take oral or sublingual medications;

 22. Inability to follow protocol-related procedures