Part I. SARS-CoV-2 triggered ‘PANIC’ attack in severe COVID-19()

Frohman, Elliot M.; Melamed, Esther; Cruz, Roberto Alejandro; Longmuir, Reid; Steinman, Lawrence; Zamvil, Scott S.; Villemarette-Pittman, Nicole R.; Frohman, Teresa C.; Parsons, Matthew S.

The COVID-19 pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constraining our freedom of movement. This respiratory tract infection is unprecedented in that it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the alveoli that are responsible for the loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In most symptomatic individuals, the reaction is a productive and mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a virus capable of producing what can only be described as a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, that then leads to a virtual collapse of the gas-exchange apparatus. Here, in Part I of a duology on the characterization and potential treatment for COVID-19, we define severe COVID-19 as a consequence of the SARS-CoV-2 virus' ability to trigger what we now designate for the first time, as a ‘Prolific Activation of a Network-Immune-Inflammatory Crisis’, or ‘PANIC’ Attack, in the alveolar tree. In Part II we describe an immunotherapeutic hypothesis worthy of the organization of a randomized clinical trial in order to ascertain whether a repurposed, generic, inexpensive, and widely available agent is capable of abolishing ‘PANIC’; thereby preventing or mitigating severe COVID-19, with monumental ramifications for world health, and the global pandemic that continues to threaten it.