In December 2019,
coronavirus disease 2019 (COVID-19), a severe respiratory illness caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The greatest impact that
COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute
respiratory failure (ARF) requiring ICU admission. Based on the assumption that
COVID-19 represented a
viral pneumonia and no anti-coronaviral
therapy existed, nearly all national and international health care societies recommended "supportive care only" avoiding other
therapies outside of randomized controlled trials, with a specific prohibition against the use of
corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of
mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line
COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of
COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working", the increasing medical journal publications and the rapidly accumulating personal clinical experiences with
COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core
therapies of
methylprednisolone,
ascorbic acid,
thiamine,
heparin and non-
antiviral co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and
COVID-19 specifically.