Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced ‘PANIC’ attack

• Authors: Elliot M Frohman, The University of Texas at Austin; Nicole R Villemarette-Pittman, LSUHSC School of Medicin; Roberto A Cruz, The University of Texas at Austin; Reid Longmuir, Vanderbilt University; Vernon Rowe, Rowe Neurology Institute; Elizabeth S Rowe, Rowe Neurology Institute; Thomas C Varkey, The University of Texas at Austin; Lawrence Steinman, Stanford University; Scott S Zamvil, University of California San Francisco; Teresa C Frohman, The University of Texas at Austin
• Journal Title: JOURNAL OF THE NEUROLOGICAL SCIENCES
• Volume: Volume 415
• Publisher: Elsevier | 2020-08-15
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.jns.2020.116935
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Opthamology
• Keywords: Cytokine; Methotrexate; Complement; Innate immunity; Adaptive immunity; Alveoli; Gas exchange; SARS-CoV-2; COVID-19; Spike protein; ACE-2 receptor

Abstract

Here, in Part II of a duology on the characterization and potential treatment for COVID-19, we characterize the application of an innovative treatment regimen for the prevention of the transition from mild to severe COVID-19, as well as detail an intensive immunotherapy intervention hypothesis. We propose as a putative randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR) rescue can abolish ‘PANIC’, thereby ‘left-shifting’ severe COVID-19 patients to the group majority of those infected with SARS-CoV-2, who are designated as having mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic properties and is a repurposed, generic, inexpensive, and widely available agent which can be administered early in the course of severe COVID-19 thus rescuing the critical and irreplaceable gas-exchange alveoli. Further, we describe a preventative treatment intervention regimen for those designated as having mild to moderate COVID-19 disease, but who exhibit features which herald the transition to the severe variant of this disease. Both of our proposed hypothesis-driven questions should be urgently subjected to rigorous assessment in the context of randomized controlled trials, in order to confirm or refute the contention that the approaches characterized herein, are in fact capable of exerting mitigating, if not abolishing, effects upon SARS-CoV-2 triggered ‘PANIC Attack’. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons which could be leveraged to more effectively prepare for the next challenge to global health.