MATH+, I-MASK+ and I-RECOVER Protocols: Overview and A Guide to the Management of COVID-19
Developed and Updated by Paul Marik, MD, FCP (SA), FRCP (C), FCCP, FCCM for the COVID-19 Critical Care Alliance (FLCCC Alliance).
This is our recommended approach to COVID-19 based on the best (and most recent) literature. This is a highly dynamic topic; therefore, we will be updating the guideline as new information emerges. Please check on the FLCCC Alliance website for updated versions of this protocol.
- Ivermectin for post-exposure prophylaxis (see ClinTrials.gov NCT04422561). 0.2 mg/kg immediately then repeat 2nd dose in 48 hours. Ivermectin is best taken with a meal or just following a meal (greater absorption).  Oropharyngeal sanitation also suggested (see section on home treatment below).
- Ivermectin for pre-exposure prophylaxis (in HCW) and for prophylaxis in high-risk individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc). 0.2 mg/kg per dose - start treatment with one dose, 2nd dose 48 hours later, then 1 dose every 7 days (i.e. weekly). [12-18] (also see ClinTrials.gov NCT04425850). We believe that bi-weekly dosing is likely the most practical, cost effective and safest prophylactic regimen. See dosing Table below and Figures 8 and 9. NB. Ivermectin has a number of potentially serious drug-drug interactions; please check for potential drug interactions at Ivermectin Drug Interactions - Drugs.com. (also see below) . The most important drug-drug interactions occur with cyclosporin, tacrolimus, antiretroviral drugs, and certain anti-fungal drugs. While ivermectin has a remarkable safety record,  fixed drug eruptions (diffuse rash) and Stevens Johnson Syndrome have rarely been reported. [20,21] While hepatitis is commonly quoted as a side effect, we are aware of a single case report of reversible hepatitis. The safety of ivermectin in pregnancy has not been determined.  Ivermectin may increase the risk of congenital malformations particularly when used in the first trimester.  US Food and Drug Administration (FDA) has classified ivermectin as pregnancy category C—i.e, “Animal reproduction studies have shown an adverse effect on the foetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks”. In pregnant patients with symptomatic COVID-19 infections the risk and benefits of ivermectin should be discussed with the patient, and informed consent obtained from the patient should the drug be prescribed. Additionally, women should be counselled that low concentrations of ivermectin are present in breast milk; the implications of this finding are unclear. 
- Vitamin D3 1000–3000 IU/day (25-75 mcg). An alternative strategy is 40 000 IU weekly. Note RDA (Recommended Daily Allowance) is 800–1000 IU/day. The safe upper-dose daily limit is likely < 4000 IU/day. Vitamin D insufficiency has been associated with an increased risk of acquiring COVID-19 and from dying from the disease. [13,25-47] Vitamin D supplementation may therefore prove to be an effective and cheap intervention to lessen the impact of this disease, particularly in vulnerable populations, i.e., the elderly, those of color, obese and those living > 45o latitude. [30-45] It is likely that the greatest benefit from vitamin D supplementation will occur in vitamin D insufficient individuals who take vitamin D prophylactically; once vitamin D insufficient individuals develop COVID-19 the benefits will likely be significantly less.  This concept is supported by a recent study which demonstrated that residents of a long-term care facility who took vitamin D supplementation had a much lower risk of dying from COVID-19.  It should be noted that Former CDC Chief Dr. Tom Frieden has stated ”Coronavirus infection risk may be reduced by Vitamin D”. https://preventepidemics.org/covid19/press/former-cdc-chiefdr-tom-frieden-coronavirus-infection-risk-may-be-reduced-by-vitamin-d/
- Vitamin C 500 – 1000 mg BID (twice daily) and Quercetin 250 mg daily. [49-61] Due to the possible drug interaction between quercetin and ivermectin (see below) these drugs should not be taken simultaneously (i.e. should be staggered morning and night). Vitamin C has important anti-inflammatory, antioxidant, and immune enhancing properties, including increased synthesis of type I interferons.[52,62,63] Quercetin has direct viricidal properties against a range of viruses, including SARS-CoV-2, and is a potent antioxidant and anti-inflammatory agent. [50,55,60,60,64-72] Quercetin is a potent inhibitor of inflammasome activation, which believed to play a major role in the pathophysiology of the COVID-19 immune dysfunction. In addition, quercetin acts as a zinc ionophore.  It is likely that vitamin C and quercetin have synergistic prophylactic benefit.  A mixed flavanoid supplement containing quercetin, green tea catechins and anthrocyanins (from berries) may be preferable to a quercetin supplement alone; [74-78] this may further minimize the risk of quercetin related side-effects. It should be noted that in vitro studies have demonstrated that quercetin and other flavonoids interfere with thyroid hormone synthesis at multiple steps in the synthetic pathway. [79-82] The use of quercetin has rarely been associated with hypothyroidism. The clinical impact of this association may be limited to those individuals with pre-existent thyroid disease or those with sub-clinical thyroidism. In women high consumption of soya was associated with elevated TSH concentrations. The effect on thyroid function may be dose dependent, hence for chronic prophylactic use we suggest that the lowest dose be taken. Quercetin should be used with caution in patients with hypothyroidism and TSH levels should be monitored. It should also be noted quercetin may have important drug-drug interactions; the most important drug-drug interaction is with cyclosporin and tacrolimus.  In patients taking these drugs it is best to avoid quercetin; if quercetin is taken cyclosporin and tacrolimus levels must be closely monitored.
- Melatonin (slow release): Begin with 0.3 mg and increase as tolerated to 6 mg at night. [1,8,86- 92]. Melatonin has anti-inflammatory, antioxidant, immunomodulating and metabolic effects that are likely important in the mitigation of COVID-19 disease.[93-95] A recent large retrospective study demonstrated that the use of melatonin in intubated patients with COVID19 significantly reduced the risk of death (HR 0.1; p=0.0000000715). It is intriguing to recognize that bats, the natural reservoir of coronavirus, have exceptionally high levels of melatonin, which may protect these animals from developing symptomatic disease.  The slow release (extended release) formulation of melatonin is preferred as it more closely replicates the normal circadian rhythm. 
- Zinc 30–50 mg/day (elemental zinc). [56,58,59,97-101] Zinc is essential for innate and adaptive immunity. In addition, Zinc inhibits RNA dependent RNA polymerase in vitro against SARSCoV-2 virus. Due to competitive binding with the same gut transporter, prolonged high dose zinc (> 50mg day) should be avoided as this is associated with copper deficiency.  Commercial zinc supplements contain 7 to 80 mg of elemental zinc, and are commonly formulated as zinc oxide or salts with acetate, gluconate, and sulfate. 220 mg zinc sulfate contains 50 mg elemental zinc.
- B complex vitamins [103-107].
- Oropharyngeal hygiene with twice daily anti-viral mouth mouth/gargle (see below).
- Optional: Famotidine 20–40 mg/day [108-114]. Low level evidence suggests that famotidine may reduce disease severity and mortality. However, the findings of some studies are contradictory. While it was postulated that famotidine inhibits the SARS-CoV-2 papainlike protease (PLpro) as well as the main protease (3CLpro) this mechanism has been disputed.  Furthermore, a number of studies have demonstrated an association between the use of proton pump inhibitors (PPI’s) with an increased risk of contracting COVID-19 and with worse outcomes. [115,116] This data suggest that famotidine may be the drug of choice when acid suppressive therapy is required.
- Optional/Experimental: Interferon-α nasal spray for health care workers .
- 50-64.9 kg - 12mg
- 65-79.9 kg - 15mg
- 80-94.9 kg - 18mg
- 95-109.9 kg - 21mg
- ≥ 110 kg - 24mg
I-MASS: Mass distribution protocol for the Prophylaxis and Early Outpatient treatment for COVID-19
- IVERMECTIN: 18 mg.  Start treatment with one dose on day 1, and then repeat weekly (every 7 days)
- VITAMIN D3: 2000 IU (50 mcg) daily
- Multivitamin: Take 1 daily
- Digital thermometer (optional)
- IVERMECTIN: 18 mg daily for 5 days
- Melatonin: 6 mg at night for 5 days
- Aspirin 81 mg daily for 5 days (unless contraindicated)
- Antiseptic mouth wash: Three times daily (gargle do not swallow); if available
- IVERMECTIN 18mg day 1 and day 3
- Use the index or middle finger; avoid the toes or ear lobe
- Only accept values associated with a strong pulse signal
- Observe readings for 30–60 seconds to identify the most common value
- Remove nail polish from the finger on which measurements are made
- Warm cold extremities prior to measurement