Dataset Information

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

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 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.

SUBMITTER: Frohman EM

PROVIDER: S-EPMC7241359 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Frohman Elliot M EM Villemarette-Pittman Nicole R NR Cruz Roberto Alejandro RA Longmuir Reid R Rowe Vernon V Rowe Elizabeth S ES Varkey Thomas C TC Steinman Lawrence L Zamvil Scott S SS Frohman Teresa C TC

Journal of the neurological sciences 20200521

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 majori ...[more]

PMID: 32534807

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Project description:Folate is a nutrient crucial for rapidly growing tissues, including developing embryos and cancer cells. Folate participates in the biosynthesis of nucleic acids, proteins, amino acids, S-adenosylmethionine, many neurotransmitters, and some vitamins. The intracellular folate pool consists of different folate adducts, which carry one-carbon units at three different oxidative states and participate in distinct biochemical reactions. Therefore, the content and dynamics of folate adducts will affect the homeostasis of the metabolites generated in these folate-mediated reactions. Currently, the knowledge on the level of each individual folate adduct in developing embryos is limited. With an improved high-performance liquid chromatography protocol, we found that tetrahydrofolate (THF), the backbone of one-carbon carrier, gradually increased and became dominant in developing zebrafish embryos. 5-methyl-tetrahydrofolate (5-CH3-THF) was abundant in unfertilized eggs but decreased rapidly when embryos started to proliferate and differentiate. 10-formyltetrahydrofolate at first increased after fertilization, and then dropped dramatically before reaching a sustained level at later stages. Dihydrofolate (DHF) slightly decreased initially and remained low throughout embryogenesis. Exposure to methotrexate significantly decreased 5-CH3-THF levels and increased DHF pools, besides causing brain ventricle anomaly. Rescuing with leucovorin partly reversed the abnormal phenotype. Unexpectedly, the level of 5-CH3-THF remained low even when leucovorin was added for rescue. Our results show that different folate adducts fluctuated significantly and differentially in concert with the physiological requirement specific for the corresponding developmental stages. Furthermore, methotrexate lowered the level of 5-CH3-THF in developing embryos, which could not be reversed with folate supplementation and might be more substantial to cellular methylation potential and epigenetic control than to nucleotide synthesis.

Project description:BackgroundPanic attacks and panic disorder can have a major impact on the mental health and wellbeing of those who experience them. People with recurrent panic attacks have increased odds of developing a mental disorder and of worsening the course of existing mental disorders. Early intervention efforts at the time that a panic attack occurs might reduce or prevent some of these associated negative outcomes. Expert consensus guidelines for high income Western countries on how to provide mental health first aid for panic attacks were published in 2009. The present study aims to redevelop these guidelines to ensure content reflects current evidence and best practice.MethodsThe Delphi consensus method was used to determine which helping strategies should be included in the redeveloped guidelines. A survey with items on how to assist someone who is having a panic attack was developed using the 2009 guidelines and a systematic search of grey and academic literature. Panellists with lived experience and professional experience rated these items to determine which helping statements should be included in the guidelines.ResultsThirty panellists completed all three surveys. Panellists rated 158 statements, with 83 statements meeting the criteria for inclusion in the redeveloped guidelines. The endorsed statements covered: what the first aider should know about panic attacks, what they should do if they think someone is having a panic attack, what they should do if they are uncertain whether the person is having a panic attack, what they should say and do if they know the person is having a panic attack and what they should do when the panic attack has ended.ConclusionThis study has resulted in a more comprehensive set of guidelines than the original version, with the endorsement of 83 helping actions, compared to 27 previously. The redeveloped guidelines provide greater detail on recognising the signs of a panic attack, providing initial assistance, communicating with someone experiencing a panic attack and supporting them to seek appropriate professional help if it is needed. The guidelines will be used in future updates of Mental Health First Aid training courses.

Dataset Information

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

Publications

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

Similar Datasets

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