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 the SARS-CoV-2 virus, 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 novel Coronavirus. 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 the SARS-CoV-2 triggering of the ‘PANIC Attack’. Confirmation of our immunotherapy hypothesis would have far-reaching ramifications for the current pandemic, along with yielding invaluable lessons from which we can more effectively prepare for the next challenge to global health.

中文翻译：

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第二部分。大剂量甲氨蝶呤联合亚叶酸对重症 COVID-19 的拯救：一种针对 SARS-CoV-2 诱发的“恐慌”攻击的免疫稳定策略

摘要在此，在关于 COVID-19 的特征和潜在治疗的双篇集的第二部分中，我们描述了创新治疗方案的应用，以预防从轻度到重度 COVID-19 的转变，并详细介绍了强化免疫疗法干预假说。我们建议作为一项假定的随机对照试验，高剂量甲氨蝶呤和亚叶酸 (HDMTX-LR) 救援可以消除“恐慌”，从而将严重的 COVID-19 患者“左移”到大多数感染 SARS-CoV 的人群-2 病毒，被指定为具有轻度甚至无症状的疾病。HDMTX-LR 具有广泛的多向性，是一种重新利用的、通用的、廉价的、和广泛可用的药物，可以在严重的 COVID-19 病程早期给药，从而挽救关键且不可替代的气体交换肺泡。此外，我们描述了一种预防性治疗干预方案，适用于那些被指定为轻度至中度 COVID-19 疾病但表现出预示着向这种新型冠状病毒的严重变体转变的特征的人。我们提出的两个假设驱动的问题都应该在随机对照试验的背景下紧急进行严格评估，以确认或反驳本文所描述的方法实际上能够发挥减轻（如果不能消除）影响的论点SARS-CoV-2 触发“恐慌袭击”。