Table 3.

The algorithm proposal for therapeutic management with antioxidants for COVID-19 patients.

Identification of the Case and Integral Study	Management by the Intensive Care Specialist	Proposed Treatment Assays	Additional Proposed Antioxidant Therapy to the Medical Management in COVID-19 Patients with Pneumonia	Drug Interactions
1. Identification of infected cases having a medical history (healthy or with simple or combined comorbidities), age, body mass index. 2. Integral laboratory tests, including total cholesterol, HDL, LDL, triglycerides, D dimer, troponins, natriuretic peptide, creatine phosphokinase, Cl, Na, K, magnesium, phosphorus. Evaluation of hepatic and renal function. 3. Chest X-ray and/or computerized tomography. 4. Cardiovascular: electrocardiogram, echocardiogram. 5. When a cardiovascular disease is present, a multidisciplinary management involving a cardiologist is suggested (this applies to all cases).	1. Antibiotics, according to requirements. A culture if an associated bacterial infection is present. 2. Mechanical ventilation. 3. Hemodynamic Management. 4. Extracorporeal membrane oxygenation if necessary (this applies to all cases).	The patient may be treated with any of the therapies suggested by the clinical assays in standard doses. Only one or a combination of two antioxidants may be applied. When the pulmonary function is compromised, a combination of NAC and vitamin C is suggested. (This applies to all cases).	NAC dose: 600 mg/24 h orally or through a nasal enteral tube for 5 days. It should not be used when there is a gastric ulcer or antecedents of asthma or a cysteine allergy.	Anti-cholinergic drugs, anti-histaminic drugs.
			MT dose: 5 mg tablet (10 capsules)/24 h orally or through a nasal enteral tube for five days. It is safe and has a low toxicity. It is contraindicated during pregnancy, diabetes mellitus and when a patient has high systemic hypertension of the blood, and care must be taken when it is used together with some antihypertensive drugs.	Sedatives, Luvox contraceptives and cocaine increase the effect of MT. Verapamil, nifedipine, caffeine, alcohol and immunosuppressors decrease the MT effect.
			Vit C dose: 1 g every 6 h orally or through a nasal enteral tube for 5 days. It should not be used in patients with gastric ulcers, falciform anemia or during pregnancy. At high doses > 3 g, it may interact with medications used in patients with diabetes mellitus, hypertension, or Parkinson’s disease.	Aluminum, estrogens, protease inhibitors, antivirals: nelfinavir amprenavir, ritonavir, saquinavir, statins, glimepiride, glipizide, metformin, pioglitazone, rosiglitazone, antihypertensive drugs.
			Vit E, dose capsules of 400 UI that are the equivalent of 400 mg every 12 h for 5 days. It should not be used when retinitis pigmentosa is present.	Simvastatin and niacin, chemotherapy, anticoagulants and antiplatelet agents and non-steroidal anti-inflammatory drugs.
			QRC, at a dose of 500 mg every 12 h. It is safe for most people, but is not contraindicated during pregnancy. The dose should be adjusted in patients with renal failure.	Quinolones, uroseptal, cyclosporine, celecoxib, diclofenac, ibuprofen, Fluvastatin, irbesartan, losartan.
Initial evaluation.	Measures that are jointly evaluated according to the initial evaluation.	Measures that are jointly evaluated according to the initial evaluation.	Pentoxifylline (vasodilator, inhibitor of IL-6), at a dose of 400 mg daily orally or IV. Patients that are intolerant to methylxanthines might not tolerate it. (The doses of the elected antioxidants and/or pentoxifylline are similar in all cases. The selection must be taken according to contraindications and drug interactions). Measures that are jointly evaluated according to the initial evaluation.	Coumarin, heparin, indandione derivatives, cefotetan, cefamandole, valproic acid and plicamycin may increase the risk of bleeding. Final evaluation.
Evaluate and Apply According to the Patient’s Comorbidities
Diabetes Mellitus with or without Hypertension NAC or MT or QRC or vit E + pentoxifylline.	Hypertension NAC or MT (if antihypertensive drugs that may interfere are not being used) or QRC or vit E (if anticoagulants are not being used) or pentoxifylline.	Obesity Without Another Comorbidity NAC or MT or QRC or vit E or vit C + pentoxifylline. Obesity + SAH + DM NAC or QRC + pentoxifylline.	Renal Insufficiency without Substitute Management (Dose Adjustment) NAC or MT or QRC or vit E + pentoxifylline. In Patients in Dialysis of Hemodialysis Standard dose.	Heart Failure NAC or MT or QRC or vit E + pentoxifylline. Monitor if the patient uses antiplatelet or anticoagulant digoxin or has an arrhythmia.
Ischemic Heart Disease NAC or MT or QRC or Vit E + Pentoxifylline Adjust if there is use of antihypertensive drugs that interact with any of them	Myocarditis NAC or MT or QRC or Vit E + Pentoxifylline On Dialysis or Hemodialysis Standard dose. Immunoglobulin should be the treatment of choice except contraindication	Arrhythmias NAC or MT or QRC or + Pentoxifylline	Chronic Obstructive Pulmonary Disease NAC or MT or QRC or + Pentoxifylline Smoking NAC or MT or QRC or Vit C + Pentoxifylline	Immune Suppression NAC or Vit E (if anticoagulants are not being used) or Pentoxifylline Cancer NAC or QRC

Abbreviations: IV = Intravenous, NAC = N-acetylcysteine, MT = melatonin, QRC = quercetin, vit C = vitamin C, vit E = vitamin E, SAH = systemic arterial hypertension, DM = diabetes mellitus, HDL = high-density lipoprotein, LDL = low-density lipoprotein.