Part II. high-dose methotrexate with leucovorin rescue for severe COVID-19: An immune stabilization strategy for SARS-CoV-2 induced 'PANIC'1 attack

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:415

Review

Frohman, Elliot M.^1,2,3  Villemarette-Pittman, Nicole R.⁴  Cruz, Roberto Alejandro¹  Longmuir, Reid^5,6  Rowe, Vernon⁷  Rowe, Elizabeth S.⁷  Varkey, Thomas C.^1,8  Steinman, Lawrence⁹  Zamvil, Scott S.^10,11  Frohman, Teresa C.^1,2,3 

[1] Univ Texas Austin, Dell Med Sch, Dept Neurol, Austin, TX 78712 USA

[2] Univ Texas Austin, Dell Med Sch, Dept Neurosurg, Austin, TX 78712 USA

[3] Univ Texas Austin, Dell Med Sch, Dept Ophthalmol, Austin, TX 78712 USA

[4] LSUHSC Sch Med, Dept Neurol, New Orleans, LA USA

[5] Vanderbilt Univ, Med Ctr, Dept Ophthalmol & Visual Sci, Nashville, TN USA

[6] Vet Affairs Med Ctr, Nashville, TN 37212 USA

[7] Rowe Neurol Inst, Lenexa, KS USA

[8] Grand Canyon Univ, Colangelo Coll Business, Phoenix, AZ USA

[9] Stanford Univ, Sch Med, Dept Neurol, Palo Alto, CA 94304 USA

[10] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[11] Univ Calif San Francisco, Program Immunol, San Francisco, CA USA

关键词: Cytokine;    Methotrexate;    Complement;    Innate immunity;    Adaptive immunity;    Alveoli;    Gas exchange;    SARS-CoV-2;    COVID-19;    Spike protein;    ACE-2 receptor;   

DOI  :  10.1016/j.jns.2020.116935

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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