Abstract

An alliance of established experts on critical care, Front Line COVID-19 Critical Care Alliance (FLCCC), has published two protocols for treatment of COVID-19. The first one, methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+), is intended for hospital and intensive care unit treatment of pulmonary phases of the disease. It is based on affordable, commonly available components: anti-inflammatory corticosteroids (methylprednisolone, "M"), high-dose vitamin C infusion (ascorbic acid, "A"), vitamin B1 (thiamine, "T"), anticoagulant heparin ("H"), antiparasitic agent ivermectin, and supplemental components ("+") including melatonin, vitamin D, elemental zinc, and magnesium. The MATH+ protocol has received scarce attention due to the World Health Organization (WHO) advising against the use of corticosteroids in the beginning of the pandemic. In addition, randomized controlled clinical trials were required as a condition for adoption of the protocol. As the hospital mortality rate of MATH+ treated patients was approximately a quarter of the rate of patients receiving a standard of care, the authors of the protocol considered performing such trials unethical. Other parties have later performed clinical trials with corticosteroids and anticoagulants, which has led to a more widespread adoption of these components.In October 2020, ivermectin was upgraded from an optional component to an essential component of the protocol. According to the authors, ivermectin is considered the first agent effective for both prophylaxis (prevention) of COVID-19 and for treatment of all phases of COVID-19 including outpatient treatment of the early symptomatic phase. Therefore, at the end of October 2020, a separate ivermectin-based I-MASK+ protocol for prophylaxis and early outpatient treatment of COVID-19 was published.

Highlights

  • The first version of the methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+) protocol created in January 2020 was based on corticosteroid hydrocortisone, vitamin C, and thiamine [1]

  • An ivermectin and doxycycline trial indicated shortened course of disease, reduction in the number of patients that remained persistently positive for reverse transcription polymerase chain reaction (RT-PCR) of COVID-19, and prevention of clinical deterioration (NCT04523831)

  • The MATH+ protocol correctly predicted the benefits of corticosteroids and anticoagulants, being ahead of its time in the first half of 2020

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Summary

Introduction

The first version of the methylprednisolone, ascorbic acid, thiamine, and heparin (MATH+) protocol created in January 2020 was based on corticosteroid hydrocortisone, vitamin C, and thiamine [1]. After the early pulmonary phase the patient is no longer considered infective; yet tests based on detection of these virus particles may give a positive result. An ivermectin and doxycycline trial indicated shortened course of disease, reduction in the number of patients that remained persistently positive for reverse transcription polymerase chain reaction (RT-PCR) of COVID-19, and prevention of clinical deterioration (NCT04523831). Another trial with the same agents (NCT04591600) yielded similar results. In the end of November, an anonymous group providing semi-automated meta-analyses published a metaanalysis of 21 ivermectin trials (ivmmeta.com) It indicated ivermectin's effectiveness for prophylaxis and treatment of all phases of COVID-19. A significant number of ivermectin trials are still ongoing or being planned [20]

Discussion
Conclusions
Disclosures
10. Marik PE
Findings
13. Liang T
17. Rizzo E

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