Targeting TNF-α for COVID-19: Recent Advanced and Controversies

Guo, Yu; Hu, Ke; Li, Yuxuan; Lü, Chao; Ling, Ken; Cai, Chuanqi; Wang, Weici; Ye, Dawei

doi:10.3389/fpubh.2022.833967

Cited by 98 publications

(91 citation statements)

References 102 publications

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“…The clinical evidence supports the role of some molecules revealed in this work in COVID-19 pathogenesis: ANGPT2 [48,49], CCL2 [50], ICAM1 [52,53], VCAM-1 [52], MIR21 [54], MMP9 [55,56], STAT3 [57], HMGB1 [58,59], SIRT1 [62,63], AGTR1 [66], APOE4 [69,70], ACE [73], CCL11 [86,87], FGF2 [89], TNF [92], PPAR-γ [95], CASP8 [115], IL8 [117], IL6 [118], PRL [119], SP1 [122], TLR4 [123], BDNF [124], CASP1 [125], CASP3 [126,127], IL18 [128], IL10 [129], TGFB1 [130], ANXA2 [131,132], HPSE [162], MAPK1 [163], CDH1 [166], FBN1 [180], GDF15 [182,183], PLAT [195][196][197], RHOA…”

Section: Discussionsupporting

confidence: 80%

“…The cytokine storm in COVID-19, associated with the severity of the disease, is characterized by the increase in TNF production; TNF is upregulated in acute lung injury and facilitates SARS-CoV-2 interaction with ACE2. Accordingly, TNF inhibitors were discussed as a therapeutic strategy in severe COVID-19 [92].…”

Section: Dpp4-related Networkmentioning

confidence: 99%

“…These 54 genes/proteins are involved in the GO biological processes related to the cytokine-mediated signaling pathway, apoptotic process, release of cytochrome c from mitochondria, T cell homeostasis, cell proliferation, and others (Table S25). Among the identified genes, TNF and CASP3 were associated with COVID-19related networks [92,127].…”

Section: Ctsl-related Networkmentioning

confidence: 99%

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Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

Saik

Климонтов

2022

IJMS

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People with diabetes are more likely to have severe COVID-19 compared to the general population. Moreover, diabetes and COVID-19 demonstrate a certain parallelism in the mechanisms and organ damage. In this work, we applied bioinformatics analysis of associative molecular networks to identify key molecules and pathophysiological processes that determine SARS-CoV-2-induced disorders in patients with diabetes. Using text-mining-based approaches and ANDSystem as a bioinformatics tool, we reconstructed and matched networks related to hyperglycemia, diabetic complications, insulin resistance, and beta cell dysfunction with networks of SARS-CoV-2-targeted proteins. The latter included SARS-CoV-2 entry receptors (ACE2 and DPP4), SARS-CoV-2 entry associated proteases (TMPRSS2, CTSB, and CTSL), and 332 human intracellular proteins interacting with SARS-CoV-2. A number of genes/proteins targeted by SARS-CoV-2 (ACE2, BRD2, COMT, CTSB, CTSL, DNMT1, DPP4, ERP44, F2RL1, GDF15, GPX1, HDAC2, HMOX1, HYOU1, IDE, LOX, NUTF2, PCNT, PLAT, RAB10, RHOA, SCARB1, and SELENOS) were found in the networks of vascular diabetic complications and insulin resistance. According to the Gene Ontology enrichment analysis, the defined molecules are involved in the response to hypoxia, reactive oxygen species metabolism, immune and inflammatory response, regulation of angiogenesis, platelet degranulation, and other processes. The results expand the understanding of the molecular basis of diabetes and COVID-19 comorbidity.

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Section: Discussionsupporting

confidence: 80%

Section: Dpp4-related Networkmentioning

confidence: 99%

Section: Ctsl-related Networkmentioning

confidence: 99%

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Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

Saik

Климонтов

2022

IJMS

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“…The release of multiple cytokines is associated with various clinical symptoms, such as the over-secretion of IFN-γ, which causes headaches, chills, dizziness, fatigue, and fever [ 28 ]. Similar to IFN-γ, TNF-α causes flu-like symptoms, along with fever, fatigue, and malaise, but it can also lead to lung damage, leaky blood vessels, heart failure, and acute-phase protein synthesis [ 29 ]. The secretion of IL-6 causes vascular leakage syndrome, activating clotting and complement pathways, leading to clear indications of cytokine release syndrome, i.e., blockage of small blood vessels.…”

Section: The Course Of the Inflammatory Process During Sars-cov-2 Inf...mentioning

confidence: 99%

The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus?

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading worldwide. For this reason, new treatment methods are constantly being researched. Consequently, new and already-known preparations are being investigated to potentially reduce the severe course of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection induces the production of pro-inflammatory cytokines and acute serum biomarkers in the host organism. In addition to antiviral drugs, there are other substances being used in the treatment of COVID-19, e.g., those with antioxidant properties, such as vitamin C (VC). Exciting aspects of the use of VC in antiviral therapy are its antioxidant and pro-oxidative abilities. In this review, we summarized both the positive effects of using VC in treating infections caused by SARS-CoV-2 in the light of the available research. We have tried to answer the question as to whether the use of high doses of VC brings the expected benefits in the treatment of COVID-19 and whether such treatment is the correct therapeutic choice. Each case requires individual assessment to determine whether the positives outweigh the negatives, especially in the light of populational studies concerning the genetic differentiation of genes encoding the solute carriers responsible forVC adsorption. Few data are available on the influence of VC on the course of SARS-CoV-2 infection. Deducing from already-published data, high-dose intravenous vitamin C (HDIVC) does not significantly lower the mortality or length of hospitalization. However, some data prove, among other things, its impact on the serum levels of inflammatory markers. Finally, the non-positive effect of VC administration is mainly neutral, but the negative effect is that it can result in urinary stones or nephropathies.

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“…On this basis, the therapeutic potential of anti-TNF-α in COVID-19 infection emerged [ 20 ]. Ongoing trials examine the use of infliximab in serious COVID-19 infection, showing promising results, and etanercept has shown some effectiveness in case reports [ 105 ]. Interestingly, a trial with adalimumab was terminated early [ 106 ].…”

Section: Introductionmentioning

confidence: 99%

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

et al. 2022

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Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the “treat-to-target” approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs.

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Targeting TNF-α for COVID-19: Recent Advanced and Controversies

Cited by 98 publications

References 102 publications

Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus?

The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era

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