Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

Ikonomidis, Ignatios; Pavlidis, George; Katsimbri, Pelagia; Lambadiari, Vaia; Parissis, John; Andreadou, Ioanna; Tsoumani, Maria; Boumpas, Dimitrios T.; Kouretas, Demetrios; Iliodromitis, Efstathios K.

doi:10.1016/j.fct.2020.111694

Cited by 53 publications

(50 citation statements)

References 49 publications

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“…A recent study by Ignaitos and group disclosed the beneficial effect of Tocilizumab on endothelial glycocalyx and myocardial efficiency via IL-6 inhibition in rheumatoid arthritis patients. The favourable outcomes like improvement of vascular permeability in these patients were correlated with an apparent beneficial effect in Covid-19, characterized by excess IL-6 release ( Ikonomidis et al, 2020 ). Lambadiari and the group explored the possibilities and mechanisms for higher risk of Covid-19 in diabetic patients.…”

Section: Delving Deeper Into the Pharmacodynamics Of Cq/hcq In Covid-mentioning

confidence: 99%

Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

Joshi

Thakur

Mayank

et al. 2021

Food and Chemical Toxicology

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Section: Delving Deeper Into the Pharmacodynamics Of Cq/hcq In Covid-mentioning

confidence: 99%

Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

Joshi

Thakur

Mayank

et al. 2021

Food and Chemical Toxicology

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“… 110 Administration of tocilizumab not only has anti-inflammatory properties, but the agent improves endothelial function leading to an increase of effective myocardial work through a reduction of inflammatory burden and oxidative stress. 111 …”

Section: Rationale For Targeting Il-6mentioning

confidence: 99%

IL-6 modulation for COVID-19: the right patients at the right time?

Ascierto

Wei

2021

J Immunother Cancer

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The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Severe COVID-19 disease is characterized by a respiratory distress syndrome accompanied by elevated levels of several systemic cytokines, in a profile that shares several features with known inflammatory pathologies such as hemophagocytic lymphohistiocytosis and cytokine release syndrome secondary to chimeric antigen receptor (CAR) T cell therapy. Based on these observations, modulation of inflammatory cytokines, particularly interleukin (IL)-6, was proposed as a strategy to mitigate severe disease. Despite encouraging recoveries with anti-IL-6 agents, especially tocilizumab from single-arm studies, early randomized trials returned mixed results in terms of clinical benefit with these interventions. Later, larger trials such as RECOVERY and REMAP-CAP, however, are establishing anti-IL-6 in combination with steroids as a potential option for hypoxic patients with evidence of hyperinflammation. We propose that a positive feedback loop primarily mediated by macrophages and monocytes initiates the inflammatory cascade in severe COVID-19, and thus optimal benefit with anti-IL-6 therapies may require intervention during a finite window of opportunity at the outset of hyperinflammation but before fulminant disease causes irreversible tissue damage—as defined clinically by C reactive protein levels higher than 75 mg/L.

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“…A 4-month randomized observational study divided 40 participants who smoked into an ENDS arm and a continued smoking arm [ 74 ]. The participants in the ENDS arm demonstrated reductions in arterial stiffness and oxidative stress that were not experienced by the participants who continued to smoke.…”

Section: Incorrect Assessment Of Cardiovascular Riskmentioning

confidence: 99%

Critical appraisal of the European Union Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) Preliminary Opinion on electronic cigarettes

O’Leary¹,

Polosa²,

Volti³

2021

Harm Reduct J

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Background In preparation for the 2021 revision of the European Union Tobacco Products Directive, the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) has posted its Preliminary Opinion on Electronic Cigarettes. They concluded that e-cigarettes only achieve a sub-optimal level of protection of human health. In this paper, we provide evidence that the Opinion’s conclusions are not adequately backed up by scientific evidence and did not discuss the potential health benefits of using alternative combustion-free nicotine-containing products as substitute for tobacco cigarettes. Methods Searches for articles were conducted in PubMed and by citation chasing in Google Scholar. Articles were also retrieved with a review of references in major publications. Primary data from World Health Organization surveys, the conclusions of reviews, and peer-reviewed non-industry studies were cited to address errors and omissions identified in the Opinion. Results The Opinion omitted reporting on the individual and population health benefits of the substitution of e-cigarettes (ENDS) for cigarette smoking. Alternative hypotheses to the gateway theory were not evaluated. Its assessment of cardiovascular risk is contradicted by numerous reviews. It cites ever-use data that do not represent current patterns of use. It did not report non-nicotine use. It presented erroneous statements on trends in ENDS prevalence. It over-emphasized the role of flavours in youth ENDS initiation. It did not discuss cessation in sufficient length. Conclusions For the delivery of a robust and comprehensive final report, the members of the Working Group of the Scientific Committee on Health, Environmental and Emerging Risks will need to consider (1) the potential health benefits of ENDS substitution for cigarette smoking, (2) alternative hypotheses and contradictory studies on the gateway effect, (3) its assessment of cardiovascular risk, (4) the measurements of frequency of use, (5) non-nicotine use, (6) the role of flavours, and (7) a fulsome discussion of cessation.

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Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

Cited by 53 publications

References 49 publications

Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update

IL-6 modulation for COVID-19: the right patients at the right time?

Critical appraisal of the European Union Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) Preliminary Opinion on electronic cigarettes

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