Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials

Horowitz, Richard; Freeman, Phyllis R.

doi:10.1016/j.mehy.2020.109851

Cited by 63 publications

(62 citation statements)

References 83 publications

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“…In another meta-analysis study, N -acetylcysteine treatment of ARDS patients shortened their stay in the intensive care unit ( Zhang et al, 2017 ). Finally, it has also been suggested that N -acetylcysteine should be used in combination with other drugs to manage ARDS ( Guo et al, 2019 ; Andreou et al, 2020 ; Horowitz and Freeman, 2020 ). Currently, several clinical trials with N -acetylcysteine to treat COVID-19 (NCT04419025, NCT04455243, NCT04374461, etc.)…”

Section: Drugs Targeting Neutrophils For Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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This review describes targeting neutrophils as a potential therapeutic strategy for acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19), a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutrophil counts are significantly elevated in patients with COVID-19 and significantly correlated with disease severity. The neutrophil-to-lymphocyte ratio can serve as a clinical marker for predicting fatal complications related to ARDS in patients with COVID-19. Neutrophil-associated inflammation plays a critical pathogenic role in ARDS. The effector functions of neutrophils, acting as respiratory burst oxidants, granule proteases, and neutrophil extracellular traps, are linked to the pathogenesis of ARDS. Hence, neutrophils can not only be used as pathogenic markers but also as candidate drug targets for COVID-19 associated ARDS.

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Section: Drugs Targeting Neutrophils For Covid-19 Associated Ardsmentioning

confidence: 99%

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

et al. 2020

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“…In addition, vitamin C potentiates the anti-oxidant effect of polyphenols, such as flavonoids [ 55 ]. Vitamin C maintains redox integrity of the cells [ 29 ], which protects lungs against oxidative stress caused by infection and inflammation [ 56 ]. Vitamin C supplement of 600 mg daily reduced incidence, severity and duration of URTI after ultramarathon race [ 57 ].…”

Section: Anti-oxidant Effect Of Vitamin Cmentioning

confidence: 99%

Overview of the possible role of vitamin C in management of COVID-19

2020

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The mainstay of management of coronavirus disease 2019 (COVID-19) is mainly supportive as to date there is no effective antiviral treatment, apart from remdesivir which has been approved by Food and Drug administration (FDA) for treatment of COVID-19, or vaccine. Supplementation with micronutrients, such as vitamins and minerals, has gained an increasing interest as part of the supportive management of COVID-19. Vitamin C levels in serum and leukocytes are depleted during the acute stage of infection owing to increased metabolic demands. High-dose vitamin C supplement helps to normalise both serum and leukocytes vitamin C levels. Vitamin C has multiple pharmacological characteristics, antiviral, anti-oxidant, anti-inflammatory and immunomodulatory effects, which make it a potential therapeutic option in management of COVID-19. The use of high dose of intravenous vitamin C for management of COVID-19 in China and the United Stated has shown promising results. There were no reported adverse reactions with the short-term use of high dose of vitamin C. Given the fact that vitamin C is cheap, available and safe drug with beneficial effects in management of viral infections and critically ill patients reported in previous clinical trials, it is sensible to add it to COVID-19 management protocol particularly if the current ongoing clinical trials testing the effect of vitamin C in management of COVID-19 show positive results.

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“…NAC exerts multiple effects on the modulation of the inflammatory and immunologic responses, including inhibition of the inflammasome pathways [interleukin-1β (IL1β), IL18, and tumor necrosis factor-ɑ (TNFɑ)], increase of T cells activity, and improvement of redox status, particularly under intense oxidative stress [183][184][185][186][187], has shown ability to diminish acute lung injuries [188], and may impair ACE2 actions when coupled with SARS-CoV-2 [189,190]. Collectively, these mechanisms convey the hypothesis of NAC as a strong candidate against COVID-19 [191,192], in particular for the second stage, aiming to prevent progression to ARDS, and is undergoing six specific clinical trials [193][194][195][196][197][198], among which five aim to prevent the occurrence of third stage in COVID-19.…”

Section: Of Moderate Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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Three novel prevention, diagnostic, and treatment options for COVID-19 urgently necessitating controlled randomized trials

Cited by 63 publications

References 83 publications

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

Overview of the possible role of vitamin C in management of COVID-19

Repurposing existing drugs for COVID-19: an endocrinology perspective

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