Involvement of IL17A and IL17RA variants in interleukin-17A levels and disease activity in ulcerative colitis.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large intestine with involvement of Th17 cells and interleukin (IL)-17A. The role of IL17A and IL17A receptor (IL17RA) variants in pathophysiology of UC still remains inconclusive. The aim was to evaluate the association between IL17A and IL17RA variants with susceptibility, IL-17A plasma levels, and endoscopic activity in UC. The study included 104 patients with UC and 213 controls. Patients were divided according to endoscopic activity (remission/mild and moderate/severe). The IL17A rs3819024 A>G and rs3819025 G>A, and IL17RA rs2241043 C>T, rs2241049 A>G, and rs6518661 G>A variants were genotyped using real time polymerase chain reaction. IL-17A plasma levels were determined using immunofluorimetric assay. Neither IL17A nor IL17RA variants were associated with UC susceptibility. The IL17A rs3819024 AG genotype was associated to high levels of IL-17 only in patients. Patients with the G allele of IL17RA rs2241049 showed 2.944 more chance of developing moderate/severe disease. The haplotype analysis showed that IL17RA rs2241049 and rs6518661 was not associated with UC susceptibility and haplotypes constituted with G allele of these variants were not associated with disease severity (p = 0.09). In conclusion, the IL17A rs3819024 AG genotype was associated with elevated IL-17A plasma levels in patients with UC but not in controls and the IL17RA rs2241049 AG+GG genotypes were associated to severity of UC. These results suggest a possible hidden interaction between the IL17A rs3819024 variant and other genetic, environmental, and epigenetic factors in the IL-17A expression that is present only in patients with UC.

Protective effects of IL18-105G > A and IL18-137C > Ggenetic variants on severity of COVID-19.

OBJECTIVE AND DESIGN: A cross-sectional study evaluated the IL18-105G > A (rs360717) and IL18-137C > G (rs187238) variants on Coronavírus Disease 2019 (COVID-19) severity. SUBJECTS AND METHODS: 528 patients with COVID-19 classifed with mild (n = 157), moderate (n = 63) and critical (n = 308) disease were genotpyed for the IL18-105G > A and IL18-137C > G variants. RESULTS: We observed associations between severe + critical COVID-19 groups (reference group was mild COVID-19) and the IL18-105G > A (p = 0.008) and IL18-137C > G (p = 0.01) variants, which remained significant after adjusting for sex, ethnicity and age. Consequently, we have examined the associations between moderate + critical COVID-19 and the genotypes of both variants using different genetic models. The IL18-105G > A was associated with severe disease (moderate + critical), with effects of the GA genotype in the codominant [Odds ratio (OR), (95 % confidence interval) 0.55, 0.34-0.89, p = 0.015], overdominant (0.56, 0.35-0.89, p = 0.014) and dominant (0.60, 0.38-0.96, p = 0.031) models. IL18-105 GA coupled with age, chest computed tomograhy scan anormalities, body mass index, heart diseases, type 2 diabetes mellitus, hypertension, and inflammation may be used to predict the patients who develop severe disease with an accuracy of 84.3 % (sensitivity: 83.3 % and specificity: 86.5 %). Therefore, the presence of the IL18-105 A allele in homozygosis or heterozygosis conferred about 44.0 % of protection in the development of moderate and severe COVID-19. The IL18-137C > G variant was also associated with protective effects in the codominant (0.55, 0.34-0.89, p = 0.015), overdominant (0.57, 0.36-0.91, p = 0.018), and dominant models (0.59, 0.37-0.93, p = 0.025). Therefore, the IL18-137 G allele showed a protective effect against COVID-19 severity. CONCLUSION: The IL18-105G > A and IL18-137C > Gvariants may contribute with protective effects for COVID-19 severity and the effects of IL18-137C > G may be modulating IL-18 production and Th1-mediated immune responses.

Effect of phthalocyanine oral and nasal antiseptic solutions on the infectivity of SARS-CoV-2 in patients with COVID-19: a randomized controlled trial.

Background: In individuals with coronavirus disease (COVID-19), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL) plays an important role in infectivity. Objectives: This study aimed to evaluate the reduction in the VL and infectivity induced by phthalocyanine mouthwash and nasal spray in patients with COVID-19. Methods: Patients with mild COVID-19 were recruited to participate in a triple-blinded randomized controlled trial. Participants were assigned to one of three groups: Group 1, non-active mouthwash and saline nasal spray (SNS); Group 2, phthalocyanine mouthwash and SNS; and Group 3 phthalocyanine mouthwash and phthalocyanine nasal spray. VL was assessed in nasopharyngeal and oropharyngeal swabs collected at the time of clinical diagnosis at baseline as well as 24 and 72 hours after starting the rinsing protocols. Findings: Forty-six participants were included in the analysis: 15, 16, and 15 in Groups 1, 2, and 3, respectively. After 72 hours, the reduction in VL was significantly higher in Group 3 (mean cycle threshold (Ct) decrease: 11.21) than in Group 1 (mean Ct decrease: 5.53). Additionally, only the mean VL in Group 3 was reduced to a non-contagious level after 72 hours. Main conclusions: Use of phthalocyanine mouthwash and nasal spray is effective at reducing SARS-CoV-2 infectivity.