JNS.jpgThe August issue of the Journal of the Neurological Sciences Vol 415 is now available online.

 

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Issue highlights

Hydroxychloroquine/ chloroquine as a treatment choice or prophylaxis for Covid-19 at the primary care level in developing countries: A Primum non Nocere dilemma

The Food and Drug Administration (FDA) warned against the use of Hydroxychloroquine or chloroquine for Covid-19 outside of a hospital or a clinical trial setting due to the risk of QT interval prolongation, ventricular tachycardia and the increased risk of these complications when combined with some antibiotics such as azithromycin.

Several studies have reported no benefit of Hydroxychloroquine or chloroquine, when used alone or with a macrolide in COVID-19 hospitalized patients. Despite these warnings, in several developing countries the official guidelines for treatment of Covid-19 patients at the primary care level recommend Hydroxychloroquine and azithromycin, among other treatments, as the first-choice for mild symptomatic Covid-19 patients, asymptomatic contacts or for prophylaxis.

In our opinion there is a primum non nocere dilemma during this Covid-19 pandemic. In order to solve this bioethical problem, we strongly recommend that a randomized controlled trial in a primary care setting be carried out as a matter of urgency in these areas of the world.


Silencing of immune activation with methotrexate in patients with COVID-19

It is becoming apparent that patients with COVID-19 are developing a wide variety of autoimmune syndromes many of which involve the nervous system. These syndromes most often occur when patients are recovering from the acute viral symptoms. Even in patients with active infection in the lungs, the inflammatory response to the viral infection can be overwhelming in some which is thought to be the major cause of acute respiratory distress syndrome or the viral pneumonia. The inflammation is also thought to mediate a hypercoagulable state leading to thromboses in multiple blood vessels and organ systems including the brain. Thus, these inflammatory syndromes are a major cause of morbidity and mortality in this patient population.


Part I. SARS-CoV-2 triggered 'PANIC'1 attack in severe COVID-19

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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.

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.


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

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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.