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

Elliot M Frohman, Nicole R Villemarette-Pittman, Roberto Alejandro Cruz, Reid Longmuir, Vernon Rowe, Elizabeth S Rowe, Thomas C Varkey, Lawrence Steinman, Scott S Zamvil, Teresa C Frohman

Journal: Journal of the neurological sciences 2020;415():116935

PMID: 32534807

Free Full Text on Elsevier Science View on PubMed

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.

Address: Department of Neurology, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America; Department of Neurosurgery, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America; Department of Ophthalmology, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America. Electronic address: [email protected].; Department of Neurology, LSUHSC School of Medicine, New Orleans, LA, United States of America. Electronic address: [email protected].; Department of Neurology, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America. Electronic address: [email protected].; Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, TN, United States of America; Veterans Affairs Medical Center, Nashville, TN, United States of America.; Rowe Neurology Institute, Lenexa, KS, United States of America. Electronic address: [email protected].; Rowe Neurology Institute, Lenexa, KS, United States of America. Electronic address: [email protected].; Department of Neurology, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America; The Colangelo College of Business, at Grand Canyon University, Phoenix, AZ, United States of America. Electronic address: [email protected].; Department of Neurology, Stanford University School of Medicine, Palo Alto, CA, United States of America. Electronic address: [email protected].; Department of Neurology and Program in Immunology, University of California San Francisco, San Francisco, CA, United States of America. Electronic address: [email protected].; Department of Neurology, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America; Department of Neurosurgery, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America; Department of Ophthalmology, The Dell Medical School, The University of Texas at Austin, Austin, TX, United States of America. Electronic address: [email protected].

DOI: 10.1016/j.jns.2020.116935

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MeSH Terms: Betacoronavirus, COVID-19, Clinical Trial Protocols as Topic, Coronavirus Infections, Disease Management, Humans, Immunosuppressive Agents, Immunotherapy, Leucovorin, Methotrexate, Pandemics, Pneumonia, Viral, SARS-CoV-2