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Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study.

ABSTRACT: Toll-like receptor 3 (TLR3) and TLR7 genes are involved in the host immune response against viral infections including SARS-COV-2. This study aimed to investigate the association between the TLR3(rs3775290) and TLR7(rs179008) polymorphisms with the prognosis and susceptibility to COVID-19 pneumonia accompanying SARS-COV-2 infection. This case-control study included 236 individuals: 136 COVID-19 pneumonia patients and 100 age and sex-matched controls. Two polymorphisms (TLR3 rs3775290 and TLR7 rs179008) were genotyped by allelic discrimination through TaqMan real-time PCR. This study also investigated predictors of mortality in COVID-19 pneumonia through logistic regression. The mutant 'T/T' genotypes and the 'T' alleles of TLR3(rs3775290) and TLR7(rs179008) polymorphisms were significantly associated with increased risk of COVID-19 pneumonia. This study did not report association between the mutant 'T/T' genotypes of TLR3(rs3775290) and TLR7(rs179008) and the disease outcome. In multivariate analysis, the independent predictors of mortality in COVID-19 pneumonia were male sex, SPO₂ ≤ 82%, INR > 1, LDH ≥ 1000 U/l, and lymphocyte count<900/mm3 (P < 0.05).

SUBMITTER: Alseoudy MM

PROVIDER: S-EPMC8767970 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study.

Alseoudy Mahmoud M MM Elgamal Mohamed M Abdelghany Dalia A DA Borg Asmaa M AM El-Mesery Ahmed A Elzeiny Dina D Hammad Maha O MO

Clinical immunology (Orlando, Fla.) 20220119

Toll-like receptor 3 (TLR3) and TLR7 genes are involved in the host immune response against viral infections including SARS-COV-2. This study aimed to investigate the association between the TLR3(rs3775290) and TLR7(rs179008) polymorphisms with the prognosis and susceptibility to COVID-19 pneumonia accompanying SARS-COV-2 infection. This case-control study included 236 individuals: 136 COVID-19 pneumonia patients and 100 age and sex-matched controls. Two polymorphisms (TLR3 rs3775290 and TLR7 rs ...[more]

PMID: 35063671

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Project description:Background: The clinical characteristics of coronavirus disease 2019 (COVID-19) have been well-studied, while effective predictors for clinical outcome and research on underlying mechanisms are scarce. Methods: Hospitalized COVID-19 pneumonia patients with definitive clinical outcome (cured or died) were retrospectively studied. The diagnostic performance of the leucocyte subsets and other parameters were compared using the area under the receiver operating characteristic curve (AUC). Further, the correlations between leucocyte subsets and inflammation-related factors associated with clinical outcome were subsequently investigated. Results: Among 95 subjects included, 56 patients were cured, and 39 died. Older age, elevated aspartate aminotransferase, total bilirubin, serum lactate dehydrogenase, blood urea nitrogen, prothrombin time, D-dimer, Procalcitonin, and C-reactive protein levels, decreased albumin, elevated serum cytokines (IL2R, IL6, IL8, IL10, and TNF-?) levels, and a decreased lymphocyte count indicated poor outcome in patients with COVID-19 pneumonia. Lymphocyte subset (lymphocytes, T cells, helper T cells, suppressor T cells, natural killer cells, T cells+B cells+NK cells) counts were positively associated with clinical outcome (AUC: 0.777; AUC: 0.925; AUC: 0.900; AUC: 0.902; AUC: 0.877; AUC: 0.918, resp.). The neutrophil-to-lymphocyte ratio (NLR), neutrophil to T lymphocyte count ratio (NTR), neutrophil percentage to T lymphocyte ratio (NpTR) effectively predicted mortality (AUC: 0.900; AUC: 0.905; AUC: 0.932, resp.). Binary logistic regression showed that NpTR was an independent prognostic factor for mortality. Serum IL6 levels were positively correlated with leucocyte count, neutrophil count, and eosinophil count and negatively correlated with lymphocyte count. Conclusion: These results indicate that leucocyte subsets predict the clinical outcome of patients with COVID-19 pneumonia with high efficiency. Non-self-limiting inflammatory response is involved in the development of fatal pneumonia.

Project description:Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity. Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples. Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19. Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.

Dataset Information

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study.

Publications

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study.

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