A group of critical-care specialists from academic institutions and major hospitals have come together to form the Front Line Covid-19 Critical Care Alliance, and they have developed the MATH+ protocol for hospital treatment of COVID-19. On July 16, Medscape took a look at this protocol. They note that, “response to the protocol among other critical care physicians is mixed, with several physicians, in interviews with Medscape Medical News, urging caution because the benefits and relative risks of the combined medications have not been tested in randomized control trials.” MATH+ is an acronym for “methylprednisolone (a steroid), ascorbic acid (vitamin C), thiamine, and heparin.” The “plus” stands for additional supplements, such as vitamin D, zinc, and melatonin. MATH+ evolved from “HAT therapy” (hydrocortisone, ascorbic acid, and thiamine) that was created by Dr. Paul Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School, for critical cases of sepsis.
MATH+, RCTs, and Heresy
When Marik and his collaborators created the protocol in March, WHO was advising against steroids for COVID-19 patients. But using a, “website and a small communications team,” the MATH+ team publicized their work. Marik indicates that his requests to evaluate the protocol to WHO, CDC, and NIH have not been answered. In recent Senate testimony, Pierre Kory, MD, MPH, “shared his positive experience using the protocol to treat patients and expressed his dismay that national healthcare organizations came out against the use of corticosteroids for COVID-19 from the early days of the pandemic based on what he called a ‘tragic error in analysis of medical data.’” Early on, the protocol was considered “heresy” for including steroids. Marik says the deaths went down after beginning the protocol, and that they have been collecting data but do not plan a RCT.
Some doctors have expressed concern that the evidence is not there for MATH+, and call for RCTs, but Dr. Marik says this would not be ethical if the doctor was confident steroids would help. And he says that since MATH+ is personalized for each patient, an RCT would be “incredibly difficult.” One critic, Dr. Hugh Cassiere, is director of critical care medicine at Northwell Health’s North Shore University Hospital in Manhasset, New York. He finds it, “very disturbing that this is being propagated,” and argues that general physicians would unthinkingly apply this protocol.
Different Problems and Different Phases
Others, in supporting the protocol have emphasized its focus on both treating different problems (e.g. hypoxia and blood clots) and recognizing that there are different phases of the COVID-19 disease. A medical ”civil war” aspect of MATH+ is vitamin C, or ascorbic acid. Vitamins have two handicaps in modern medicine; they have association with “new age” quackery and they are low-profit. Critics point to recent studies showing a lack of effect in treating sepsis with the vitamin. In response, Marik has argued that the vitamin was given too late in the course of disease to be effective. The Alliance has posted studies supporting the underlying science of their MATH+ protocols here.
Paul E. Marik, MD, FCCP, FCCM