Considerations for Statin Therapy in Patients with COVID‐19

Dashti‐Khavidaki, Simin; Khalili, Hossein

doi:10.1002/phar.2397

Cited by 100 publications

(97 citation statements)

References 21 publications

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“…The inflammatory cytokine storm plays an important role in the development of COVID-19 in patients [10]. TNF-α and IL-6 are important inflammatory cytokines, and we found that the levels of TNF-α and IL-6 in the plasma of patients with COVID-19 were significantly increased and positively correlated with the severity of the disease.…”

Section: Plos Onementioning

confidence: 55%

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19

et al. 2020

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To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.

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Section: Plos Onementioning

confidence: 55%

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19

et al. 2020

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“…Furthermore, human SARS-CoV-2 at the whole genome level is >95% identical to a bat coronavirus (RaTG13), the natural reservoir host for multiple coronaviruses (1, 4,5). Given the rapid appearance and spread of this virus, there is no current validated vaccine or SARS-CoV-2specific targeting therapy clinically approved although statins, heparin, and steroids look promising for lowering fatality rates and antivirals likely reduce the duration of symptomatic disease presentation (6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor

Zhao

Praissman

Grant

et al. 2020

Preprint

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SUMMARYThe current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamic simulations of each glycoprotein alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.

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“…To that effect several anti-cytokine therapies have been proposed and are now in clinical trials. These include anti-IL-6 receptor antibody tocilizumab 9,10,36 , colchicine, an agent that can potentially in uence levels of IL-6 and other cytokines 37 , chroloquine 13 , metronidazole 38 , and statins 39 , as well as melatonin as an antiin ammatory adjuvant therapy 4 . Chloroquine has some immunomodulatory effects, potentially suppressing the production and release of TNF-α and IL-6 13 .…”

Section: Resultsmentioning

confidence: 99%

Fighting the storm: novel anti- TNFα and anti-IL-6 C. sativa lines to tame cytokine storm in COVID-19

Kovalchuk

Rodriguez-Juarez

Ilnytskyy

et al. 2020

Preprint

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The main aspects of severe COVID-19 disease pathogenesis include the increasing hyper-induction of proinflammatory cytokines, also known as ‘cytokine storm’, that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of the cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed that can efficiently and swiftly block TNFα, IL-6, and the inflammatory cytokine cascade in order to curb inflammation and prevent fibrosis, and lead to disease remission.Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of our novel C. sativa lines may be used to modulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis. To analyze the anti-inflammatory effects of novel C. sativa lines, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis lines.We noted that out of seven studied extracts of novel C. sativa lines, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. Most importantly, one of the tested extracts had no effects at all, and one exerted effects that may be deleterious, signifying that cannabis is not generic and cultivar selection must be based on thorough pre-clinical studies.The observed pronounced inhibition of TNFα and IL-6 is the most important finding, as these molecules are currently considered to be the main actionable targets in COVID-19 cytokine storm and ARDS pathogenesis. Many currently trialed agents, such as anti-TNFα and anti-IL-6 biologics are expensive and cause an arrays of side effects. On the other hand, anti-TNFα and anti-IL-6 cannabis extracts that are generally regarded as safe (GRAS) modalities can be a useful addition to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and ‘inflammaging’ - the inflammatory underpinning of aging and frailty.

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Considerations for Statin Therapy in Patients with COVID‐19

Cited by 100 publications

References 21 publications

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19

The changes of the peripheral CD4+ lymphocytes and inflammatory cytokines in Patients with COVID-19

Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor

Fighting the storm: novel anti- TNFα and anti-IL-6 C. sativa lines to tame cytokine storm in COVID-19

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