The time to offer treatments for COVID-19.

Background: COVID-19 has several overlapping phases. Treatments to date have focused on the late stage of disease in hospital. Yet, the pandemic is by propagated by the viral phase in out-patients. The current public health strategy relies solely on vaccines to prevent disease.Methods: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results.Results: As of 2/15/2021, we found 111 publications reporting findings on 14 classes of agents, and 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care. Remdesivir and high titer convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries.Expert Opinion: Vaccines and antibodies are highly antigen specific, and new SARS-Cov-2 variants are appearing. We call on public health authorities to authorize treatments with known low-risk and possible benefit for outpatients in parallel with universal vaccination.

The History of Methylprednisolone, Ascorbic Acid, Thiamine, and Heparin Protocol and I-MASK+ Ivermectin Protocol for COVID-19.

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.