Part I. SARS-CoV-2 triggered 'PANIC' attack in severe COVID-19

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:415

Review

Frohman, Elliot M.^1,2,3  Villemarette-Pittman, Nicole R.⁴  Melamed, Esther¹  Cruz, Roberto Alejandro¹  Longmuir, Reid^5,6  Varkey, Thomas C.^1,7  Steinman, Lawrence⁸  Zamvil, Scott S.^9,10  Frohman, Teresa C.^1,2,3 

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

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

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

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

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

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

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

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

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

[10] 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-r;   

DOI  :  10.1016/j.jns.2020.116936

来源: Elsevier

【 摘 要 】

The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse of social and economic infrastructure, as well as constrained our freedom of movement. This respiratory tract infection is nefarious in how it targets the most distal and highly vulnerable aspect of the human bronchopulmonary tree, specifically, the delicate yet irreplaceable 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 disease is a mild immune-mediated syndrome, with limited damage to the lung tissues. About 20% of those affected experience a disease course characterized by a cataclysmic set of immune activation responses that can culminate in the diffuse and irreversible obliteration of the distal alveoli, leading 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 ability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 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.

【 授权许可】

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