Association of TNF-α G-308 a Promoter Polymorphism with the Course and Outcome of COVID-19 Patients

Saleh, Ahmed; Sultan, Ahmed; Elashry, Mohamed A; Farag, Ahmed; Mortada, Metwaly Ibrahim; Ghannam, Mayada A.; Saed, Ahmed M; Ghoneem, Sayed

doi:10.1080/08820139.2020.1851709

Cited by 60 publications

(66 citation statements)

References 29 publications

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“…Another concern is that TNF-α inhibitors can reactivate LTBI in a vulnerable population by their immunosuppressive nature ( 170 , 171 ). Furthermore, a polymorphism in TNF-α (G308A) was shown to be associated with increased susceptibility to SARS-CoV-2 infection and severe disease symptoms among COVID-19 cases ( 172 ). Therefore, it is crucial to screen the COVID-19 patients for LTBI and additional factors, such as genetic predisposition, before starting anti-TNF-α antibody therapy for COVID-19 patients ( Fig.…”

Section: Immunotherapy To Dampen Cytokine Storm In Covid-19mentioning

confidence: 99%

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

2021

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SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a rapidly evolving pandemic worldwide with at least 68 million COVID-19-positive cases and a mortality rate of about 2.2%, as of 10 December 2020. About 20% of COVID-19 patients exhibit moderate to severe symptoms. Severe COVID-19 manifests as acute respiratory distress syndrome (ARDS) with elevated plasma proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), C-X-C motif chemokine ligand 10 (CXCL10/IP10), macrophage inflammatory protein 1 alpha (MIP-1α), and chemokine (C-C motif) ligand 2 (CCL2), with low levels of interferon type I (IFN-I) in the early stage and elevated levels of IFN-I during the advanced stage of COVID-19. Most of the severe and critically ill COVID-19 patients have had preexisting comorbidities, including hypertension, diabetes, cardiovascular diseases, and respiratory diseases. These conditions are known to perturb the levels of cytokines, chemokines, and angiotensin-converting enzyme 2 (ACE2), an essential receptor involved in SARS-CoV-2 entry into the host cells. ACE2 downregulation during SARS-CoV-2 infection activates the angiotensin II/angiotensin receptor (AT1R)-mediated hypercytokinemia and hyperinflammatory syndrome. However, several SARS-CoV-2 proteins, including open reading frame 3b (ORF3b), ORF6, ORF7, ORF8, and the nucleocapsid (N) protein, can inhibit IFN type I and II (IFN-I and -II) production. Thus, hyperinflammation, in combination with the lack of IFN responses against SARS-CoV-2 early on during infection, makes the patients succumb rapidly to COVID-19. Therefore, therapeutic approaches involving anti-cytokine/anti-cytokine-signaling and IFN therapy would favor the disease prognosis in COVID-19. This review describes critical host and viral factors underpinning the inflammatory “cytokine storm” induction and IFN antagonism during COVID-19 pathogenesis. Therapeutic approaches to reduce hyperinflammation and their limitations are also discussed.

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Section: Immunotherapy To Dampen Cytokine Storm In Covid-19mentioning

confidence: 99%

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

2021

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“…In Egypt, they reached 177,543 confirmed cases and 10,298 deaths [22]. Developing countries face a critical financial problem with their limited resources that highlights the urgent need for the identification of high-risk patients who develop complications to receive timely and effective therapeutic regimens [23]. A study by Ellinghaus et al has tested for association between >8 million single nucleotide polymorphisms (SNPs) and the development of respiratory failure in COVID-19 patients [24].…”

Section: Discussionmentioning

confidence: 99%

Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients

Agwa

Kamel

Elghazaly

et al. 2021

Genes

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. Aim: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like–1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. Methods: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. Results: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. Conclusion: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

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“… [65] TNF-α TNF-α is a central element in the host defense response. [66] TLR7 TLR7 is a crucial components in the initiation of innate immune responses to a variety of pathogens, causing the production of pro-inflammatory cytokines (TNF-α, IL-1, and IL-6) and type I and II Interferons (IFNs), which are responsible for innate antiviral responses. [67] ApoE ApoE e4 not only affects lipoprotein function, but also moderates macrophage pro −/anti-inflammatory phenotypes.…”

Section: Genetic Polymorphisms Affecting the Immune Response Against Covid-19 ( Table 2 )mentioning

confidence: 99%

Host polymorphisms and COVID-19 infection

Delanghe

Speeckaert

2022

Advances in Clinical Chemistry

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Association of TNF-α G-308 a Promoter Polymorphism with the Course and Outcome of COVID-19 Patients

Cited by 60 publications

References 29 publications

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis

Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients

Host polymorphisms and COVID-19 infection

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