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.