Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics.

Current guidelines prioritize the use of the Azvudine in coronavirus disease 2019 (COVID-19) patients. However, the clinical effectiveness of Azvudine in real-world studies was lacking, despite the clinical trials showed shorter time of nucleic acid negative conversion. To evaluate the clinical effectiveness following Azvudine treatment in hospitalized COVID-19 patients, we identified 1505 hospitalized COVID-19 patients during the study period, with a follow-up of up to 29 days. After exclusions and propensity score matching, we included 226 Azvudine recipients and 226 matched controls. The lower crude incidence rate of composite disease progression outcome (4.21 vs. 10.39 per 1000 person-days, P=0.041) and all-cause mortality (1.57 vs. 6.00 per 1000 person-days, P=0.027) were observed among Azvudine recipients compared with matched controls. The incidence rates of initiation of invasive mechanical ventilation were also statistically different between the groups according to the log-rank tests (P=0.020). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome (hazard ratio [HR]: 0.43; 95% confidence interval [CI]: 0.18 to 0.99) and all-cause death (HR: 0.26; 95% CI: 0.07 to 0.94) compared with matched controls. Subgroup analyses indicated robustness of the point estimates of HRs (ranged from 0.14 to 0.84). Notably, male Azvudine recipients had a stronger effectiveness than female recipients with respect to both composite outcome and all-cause death. These findings suggest that Azvudine treatment showed substantial clinical benefits in hospitalized COVID-19 patients, and should be considered for use in this population of patients.

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The ratio between plasma kynurenine (Kyn) and tryptophan (Trp) serves as a marker of indoleamine 2,3-dioxygenase, a critical immunomodulatory molecule. Simultaneous detection of the two markers may be performed using high-pressure liquid chromatography (HPLC). However, for uremic patients, the conventional detection method may be affected by a range of accumulated toxins. The current study aimed to establish a method for the simultaneous measurement of Kyn and Trp in patients following maintenance hemodialysis via HPLC-ultraviolet detection. The procedure involved the use of a SinoChrom ODS-BP C18 column (4.6×150 mm; inner diameter, 4.5 μm) and a mobile phase of 15 mmol/l sodium acetate acetic acid solution (containing 5% acetonitrile, pH 4.8). The modified method was verified using plasma samples from 10 healthy controls and 91 maintenance hemodialysis patients. The results demonstrated that the modified method was successful in simultaneously detecting the concentrations of Trp and Kyn in the healthy controls and maintenance hemodialysis patients. The method is simple, fast, accurate and suitable for clinical and research purposes in maintenance hemodialysis patients.

IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7-CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

Current guidelines prioritize the use of the Azvudine in coronavirus disease 2019 (COVID-19) patients. However, the clinical effectiveness of Azvudine in real-world studies was lacking, despite the clinical trials showed shorter time of nucleic acid negative conversion. To evaluate the clinical effectiveness following Azvudine treatment in hospitalized COVID-19 patients, we identified 1505 hospitalized COVID-19 patients during the study period, with a follow-up of up to 29 days. After exclusions and propensity score matching, we included 226 Azvudine recipients and 226 matched controls. The lower crude incidence rate of composite disease progression outcome (4.21 vs. 10.39 per 1000 person-days, P=0.041) and all-cause mortality (1.57 vs. 6.00 per 1000 person-days, P=0.027) were observed among Azvudine recipients compared with matched controls. The incidence rates of initiation of invasive mechanical ventilation were also statistically different between the groups according to the log-rank tests (P=0.020). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome (hazard ratio [HR]: 0.43; 95% confidence interval [CI]: 0.18 to 0.99) and all-cause death (HR: 0.26; 95% CI: 0.07 to 0.94) compared with matched controls. Subgroup analyses indicated robustness of the point estimates of HRs (ranged from 0.14 to 0.84). Notably, male Azvudine recipients had a stronger effectiveness than female recipients with respect to both composite outcome and all-cause death. These findings suggest that Azvudine treatment showed substantial clinical benefits in hospitalized COVID-19 patients, and should be considered for use in this population of patients.

Indoleamine 2,3-dioxygenase (IDO) has emerged as a pivotal enzyme for mediating immune tolerance. Because IDO metabolizes tryptophan into kynurenine, the plasma kynurenine/tryptophan (Kyn/Trp) ratio has been widely used as a marker of systemic IDO. Here, we evaluated the clinical value of using the plasma Kyn/Trp ratio to estimate cell-mediated immune responses to tuberculin skin testing and risk of new bacterial infection. We also compared the Kyn/Trp ratio to a novel IDO marker, the IDO median fluorescence index (MFI) of peripheral blood mononuclear cells, which was determined by flow cytometry. In 228 patients from two hemodialysis centers, the two IDO markers were higher in patients than in healthy controls but were not correlated with each other. In vitro experiments demonstrated that peripheral blood mononuclear cells could not metabolize tryptophan into kynurenine, indicating that the increased Kyn/Trp ratio was IDO-independent. Skin induration diameters of tuberculin skin testing were correlated with the IDO MFI (negatively), but not the Kyn/Trp ratio. Further, in a 24-month prospective cohort, the Kyn/Trp ratio was not correlated with clinical infection. Alternatively, patients with a higher IDO MFI had a lower accumulative infection-free survival rate. Using a Cox proportional hazard model, it was also revealed that a higher IDO MFI was significantly associated with new bacterial infection. Taken together, these results indicate that the Kyn/Trp ratio is not a reliable circulating IDO marker in hemodialysis patients. However, the IDO MFI reflects an immunocompromised state and thus might be a potential clinical marker of bacterial infection.