COX2 inhibition in the treatment of COVID-19: Review of literature to propose repositioning of celecoxib for randomized controlled studies

Bağhaki, Semih; Yalcin, Can Ege; Baghaki, Sema; Aydin, Servet Yekta; Dağhan, Başak; Yavuz, Ersin

doi:10.1016/j.ijid.2020.09.1466

Cited by 59 publications

(49 citation statements)

References 37 publications

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“…Indeed, chronic low-grade inflammation has a negative impact on host immunity, as elevated inflammatory responses are detrimental for vaccine efficacy against influenza [ 33 ] or yellow fever [ 34 ]. In this context, clinically approved drugs with immunomodulatory properties such as metformin, imiquimod [ 35 ] and anti-inflammatory drugs (e.g., aspirin and NSAIDS) may represent attractive approaches to increase efficacy of vaccines by transiently alleviating chronic low-grade inflammation prior to vaccination [ 36 , 37 ]. Further, inflammaging may have multiple health consequences by fueling age-associated diseases including metabolic syndrome, cardiovascular disease, sarcopenia, cancer, and neurodegenerative diseases as most if not all age-related disorders share an inflammatory signature.…”

Section: General Hallmarks Of Immune Agingmentioning

confidence: 99%

The aging gut microbiome and its impact on host immunity

2021

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The microbiome plays a fundamental role in the maturation, function, and regulation of the host-immune system from birth to old age. In return, the immune system has co-evolved a mutualistic relationship with trillions of beneficial microbes residing our bodies while mounting efficient responses to fight invading pathogens. As we age, both the immune system and the gut microbiome undergo significant changes in composition and function that correlate with increased susceptibility to infectious diseases and reduced vaccination responses. Emerging studies suggest that targeting age-related dysbiosis can improve health- and lifespan, in part through reducing systemic low-grade inflammation and immunosenescence—two hallmarks of the aging process. However—a cause and effect relationship of age-related dysbiosis and associated functional declines in immune cell functioning have yet to be demonstrated in clinical settings. This review aims to (i) give an overview on hallmarks of the aging immune system and gut microbiome, (ii) discuss the impact of age-related changes in the gut commensal community structure (introduced as microb-aging) on host-immune fitness and health, and (iii) summarize prebiotic- and probiotic clinical intervention trials aiming to reinforce age-related declines in immune cell functioning through microbiome modulation or rejuvenation.

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Section: General Hallmarks Of Immune Agingmentioning

confidence: 99%

The aging gut microbiome and its impact on host immunity

2021

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“…Therefore, it is essential to define the clinical conditions of each patient with COVID-19 and identify the most appropriate treatment for each disease stage based on laboratory data essential to define the evolution of the infection [7,9,22,23]. In patients where the presence of few symptoms is prevalent (pauci-symptomatic subjects), the use of paracetamol, aspirin, and other cyclooxygenase-2 (COX2) inhibitors, appears to be more appropriate [159]. The role of aspirin is being investigated in patients with COVID-19 in RECOVERY trial [160].…”

Section: Covid Treatment Strategy Based On Pathogenetic Mechanismsmentioning

confidence: 99%

COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?

2021

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Improving early diagnosis along with timely and effective treatment of COVID-19 are urgently needed. However, at present, the mechanisms underlying disease spread and development, defined prognosis, and immune status of patients with COVID-19 remain to be determined. Patients with severe disease state exhibit a hyperinflammatory response associated with cytokine storm syndrome, hypercoagulability, and depressed cell-mediated immunity. These clinical manifestations, sharing similar pathogenesis, have been well-studied in patients with advanced ovarian cancer. The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders.The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death. These events are similar to those observed in advanced ovarian cancer which share similar pathogenesis mediated primarily by Interleukin-6, which is, as well demonstrated in ovarian cancer, the key cytokine driving the immunopathology, related systemic symptoms, and patient prognosis.Consistent with findings in other disease models with similar immunopathology, such as advanced ovarian cancer, treatment of severe COVID-19 infection should target inflammation, oxidative stress, coagulation disorders, and immunodepression to improve patient outcome. Correctly identifying disease stages, based on available laboratory data, and developing a specific protocol for each phase is essential for effective treatment.

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“…However, it was demonstrated that resveratrol, through upregulation of Sirt1 activity in rheumatoid arthritis synovial fibroblasts, suppressed the bradykinin-induced COX-2/PGE2 production ( 85 ). SARS-Cov-2 infection causes local and systemic inflammation mediated also by COX-2 eicosanoid products with metabolic dysfunction and tissue damage ( 86 ) Therefore, the resveratrol-induced inhibition of bradykinin-induced COX-2/PGE2 production might be a valuable adjunct anti-inflammatory activity in Covid-19 ( 87 ).…”

Section: Resveratrol Activities On Pathogenetic Mechanisms Involved Imentioning

confidence: 99%

“…Amongst aerosolized suspensions, a nasal spray containing carboxymethylated (1,3/1,6)-β-D-glucan (CM-glucan) combined with resveratrol has been produced and is commercially available for clinical use ( 90 ). β-glucans are high molecular weight polysaccharides acting as “biological response modifiers”, as they can stimulate the immune system exerting anti-viral activities ( 87 ). The combination with CM-glucan greatly improves resveratrol stability in aqueous solutions and, acting in synergy, enhances its biological activities ( 90 ).…”

Section: Resveratrol Pharmacokinetics and Bioavailabilitymentioning

confidence: 99%

Can Resveratrol-Inhaled Formulations Be Considered Potential Adjunct Treatments for COVID-19?

et al. 2021

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The pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has led to an extraordinary threat to the global healthcare system. This infection disease, named COVID-19, is characterized by a wide clinical spectrum, ranging from asymptomatic or mild upper respiratory tract illness to severe viral pneumonia with fulminant cytokine storm, which leads to respiratory failure. To improve patient outcomes, both the inhibition of viral replication and of the unwarranted excessive inflammatory response are crucial. Since no specific antiviral drug has been proven effective for the treatment of patients and the only upcoming promising agents are monoclonal antibodies, inexpensive, safe, and widely available treatments are urgently needed. A potential anti-inflammatory molecule to be evaluated, which possesses antiviral activities in several experimental models, is the polyphenol resveratrol. This compound has been shown to inhibit SARS-CoV-2 replication in human primary bronchial epithelial cell cultures and to downregulate several pathogenetic mechanisms involved in COVID-19 severity. The use of resveratrol in clinical practice is limited by the low bioavailability following oral administration, due to the pharmacokinetic and metabolic characteristics of the molecule. Therefore, topical administration through inhaled formulations could allow us to achieve sufficiently high concentrations of the compound in the airways, the entry route of SARS-CoV-2.

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COX2 inhibition in the treatment of COVID-19: Review of literature to propose repositioning of celecoxib for randomized controlled studies

Cited by 59 publications

References 37 publications

The aging gut microbiome and its impact on host immunity

The aging gut microbiome and its impact on host immunity

COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?

Can Resveratrol-Inhaled Formulations Be Considered Potential Adjunct Treatments for COVID-19?

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