Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study.

Background: As the COVID-19 pandemic continues to spread, the number of associated deaths continues to increase, especially among those with pre-existing conditions. Azvudine is recommended as a priority treatment for patients with COVID-19, but its efficacy in patients with pre-existing conditions is unknown. Methods: This is a single-centre, retrospective cohort study between December 5, 2022 and January 31, 2023 in Xiangya Hospital of Central South University in China to evaluate the clinical efficacy of Azvudine in hospitalised patients with COVID-19 and pre-existing conditions. Patients with Azvudine and controls were propensity score-matched (1:1) for age, gender, vaccination status, time from symptom onset to treatment exposure, severity at admission, concomitant treatments initiated at admission. The primary outcome was a composite outcome of disease progression, and the secondary outcome was each of these individual disease progression outcomes. The univariate Cox regression model was used to estimate a hazard ratio (HR) with 95% confidence interval (CI) for each result between the groups. Findings: We identified 2118 hospitalised patients with COVID-19 during the study period, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 245 Azvudine recipients and 245 matched controls. Azvudine recipients had lower crude incidence rate of composite disease progression outcome compared with matched controls (7.125/1000 person-days vs. 16.004/1000 person-days, P = 0.018). There was no significant difference in all-cause death between these two groups (1.934/1000 person-days vs. 4.128/1000 person-days, P = 0.159). Azvudine treatment was associated with significantly lower risks of composite disease progression outcome compared with matched controls (HR: 0.49; 95% CI: 0.27-0.89, P = 0.016). A significant difference in all-cause death was not found (HR: 0.45; 95% CI: 0.15-1.36, P = 0.148). Interpretation: These findings indicate that Azvudine therapy showed substantial clinical benefits in hospitalised patients with COVID-19 and pre-existing conditions, and should be considered for this population of patients. Funding: This work was supported by the National Natural Science Foundation of China (Grant Nos. 82103183 to F. Z., 82102803, 82272849 to G. D.), National Natural Science Foundation of Hunan Province (Grant Nos. 2022JJ40767 to F. Z., 2021JJ40976 to G. D.), Huxiang Youth Talent Program (Grant Nos. 2022RC1014 to M.S.) and Ministry of Industry and Information Technology of China (Grant Nos. TC210804V to M.S.).

Real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19: A retrospective cohort study.

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. These findings suggest that Azvudine treatment showed effectiveness in hospitalized COVID-19 patients compared with nirmatrelvir-ritonavir in terms of composite disease progression outcome.

Correlation between CD4 T-Cell Counts and Seroconversion among COVID-19 Vaccinated Patients with HIV: A Meta-Analysis.

OBJECTIVE: To evaluate the potential factors for predicting seroconversion due to the coronavirus disease 2019 (COVID-19) vaccine in people living with HIV (PLWH). METHOD: We searched the PubMed, Embase and Cochrane databases for eligible studies published from inception to 13th September 2022 on the predictors of serologic response to the COVID-19 vaccine among PLWH. This meta-analysis was registered with PROSPERO (CRD42022359603). RESULTS: A total of 23 studies comprising 4428 PLWH were included in the meta-analysis. Pooled data demonstrated that seroconversion was about 4.6 times in patients with high CD4 T-cell counts (odds ratio (OR) = 4.64, 95% CI 2.63 to 8.19) compared with those with low CD4 T-cell counts. Seroconversion was about 17.5 times in patients receiving mRNA COVID-19 vaccines (OR = 17.48, 95% CI 6.16 to 49.55) compared with those receiving other types of COVID-19 vaccines. There were no differences in seroconversion among patients with different ages, gender, HIV viral load, comorbidities, days after complete vaccination, and mRNA type. Subgroup analyses further validated our findings about the predictive value of CD4 T-cell counts for seroconversion due to COVID-19 vaccines in PLWH (OR range, 2.30 to 9.59). CONCLUSIONS: The CD4 T-cell counts were associated with seroconversion in COVID-19 vaccinated PLWH. Precautions should be emphasized in these patients with low CD4 T-cell counts, even after a complete course of vaccination.

Clinical characteristics and outcomes of patients with COVID-19 and psoriasis.

To summarize the clinical characteristics and explore the role of treatment types in outcomes among psoriasis patients with coronavirus disease 2019 (COVID-19). The principal summary measures were pooled prevalence and risk ratio (RR) with 95% confidential interval (CI). R statistic software was used for all the analysis. A total of 19 studies including 4073 psoriasis patients with COVID-19 were eligible for the meta-analysis. The overall hospitalization rate is about 20.2% (95% CI: 12.7%-28.7%), and changed to be 18.0% (95% CI: 9.9%-27.6%) or 14.1% (95% CI: 5.9%-24.6%) after systemic or biologic treatment. Moreover, the overall fatality rate is 1.5% (95% CI: 0.4%-3.0%), and turned to be 0.7% (95% CI: 0%-2.0%) or 0.5% (95% CI: 0%-2.2%) after systemic or biologic therapy. Notably, a lower hospitalization RR was found in patients receiving biologic therapy than those receiving other treatments (RR = 0.62, 95% CI: 0.42-0.94). The results were consistent after sensitivity analysis and trim-and-fill analysis. Systemic, especially biologic therapy could lessen the clinical severity in psoriasis patients with COVID-19. Our finding will help to guide current recommendations and provide a reference for clinical decision-making.

Clinical Significance of Plasma D-Dimer in COVID-19 Mortality.

It is not clear whether D-dimer can be an independent predictor of coronavirus disease 2019 (COVID-19) mortality, and the cut-off of D-dimer for clinical use remains to be determined. Therefore, a comprehensive analysis is still necessary to illuminate the clinical significance of plasma D-dimer in COVID-19 mortality. We searched PubMed, Embase, Cochrane Library, and Scopus databases until November 2020. STATA software was used for all the statistical analyses. The identifier of systematic review registration was PROSPERO CRD42020220927. A total of 66 studies involving 40,614 COVID-19 patients were included in our meta-analysis. Pooled data showed that patients in high D-dimer group had poor prognosis than those in low D-dimer group [OR = 4.52, 95% CI = (3.61, 5.67), P < 0.001; HR = 2.81, 95% CI = (1.85, 4.27), P < 0.001]. Sensitivity analysis, pooled data based on different effect models and the Duval and Tweedie trim-and-fill method did not change the conclusions. Subgroup analyses stratified by different countries, cutoffs, sample size, study design, and analysis of OR/HR still keep consistent conclusions. D-dimer was identified as an independent predictor for COVID-19 mortality. A series of values including 0.5 µg/ml, 1 µg/ml, and 2 µg/ml could be determined as cutoff of D-dimer for clinic use. Measurement and monitoring of D-dimer might assist clinicians to take immediate medical actions and predict the prognosis of COVID-19.

A predictive model for the severity of COVID-19 in elderly patients.

Elderly patients with coronavirus disease 2019 (COVID-19) are more likely to develop severe or critical pneumonia, with a high fatality rate. To date, there is no model to predict the severity of COVID-19 in elderly patients. In this study, patients who maintained a non-severe condition and patients who progressed to severe or critical COVID-19 during hospitalization were assigned to the non-severe and severe groups, respectively. Based on the admission data of these two groups in the training cohort, albumin (odds ratio [OR] = 0.871, 95% confidence interval [CI]: 0.809 - 0.937, P < 0.001), d-dimer (OR = 1.289, 95% CI: 1.042 - 1.594, P = 0.019) and onset to hospitalization time (OR = 0.935, 95% CI: 0.895 - 0.977, P = 0.003) were identified as significant predictors for the severity of COVID-19 in elderly patients. By combining these predictors, an effective risk nomogram was established for accurate individualized assessment of the severity of COVID-19 in elderly patients. The concordance index of the nomogram was 0.800 in the training cohort and 0.774 in the validation cohort. The calibration curve demonstrated excellent consistency between the prediction of our nomogram and the observed curve. Decision curve analysis further showed that our nomogram conferred significantly high clinical net benefit. Collectively, our nomogram will facilitate early appropriate supportive care and better use of medical resources and finally reduce the poor outcomes of elderly COVID-19 patients.

Prognostic value of liver biochemical parameters for COVID-19 mortality.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has brought great challenges to global public health. However, a comprehensive analysis of the relationship between liver biochemical parameters and COVID-19 mortality is quite limited. METHODS: We searched the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, Scopus, Wanfang and China National Knowledge Infrastructure database until May 5, 2020. STATA software was used for the statistical analyses. RESULTS: A total of 25 studies involving 5971 COVID-19 patients were included in our analysis. Compared with non-survivors, survivors had lower levels of aspartate aminotransferase (AST) (weighted mean difference [WMD]=-16.71U/L, 95%CI=[-21.03,-12.40], P<0.001), alanine transaminase (ALT) (WMD=-5.20U/L, 95%CI=[-8.00,-2.41], P<0.001), total bilirubin (TBIL) (WMD=4.40µmol/L, 95%CI=[-5.11,-3.70], P<0.001) and lactic dehydrogenase (LDH) (WMD=-252.44U/L, 95%CI=[-289.57,-215.30], P<0.001), and higher albumin (ALB) level (WMD=4.47g/L, 95%CI=[3.47,5.47], P<0.001). Besides, survivors had lower proportions of these abnormally increased parameters (AST: OR=0.25, 95%CI=[0.15,0.41], P<0.001; ALT: OR=0.49, 95%CI=[0.37,0.64], P<0.001; TBIL: (OR=0.20, 95%CI=[0.12,0.34], P<0.001; LDH, OR=0.09, 95%CI=[0.06,0.14], P<0.001), and lower proportion of abnormally decreased ALB (OR=0.16, 95%CI=[0.07,0.38], P<0.001). Meta-analysis based on standard mean difference and sensitivity analysis did not change the conclusions. Egger test did not detect the presence of publication bias. CONCLUSIONS: Liver biochemical parameters were strongly correlated with COVID-19 mortality. Measurement of these liver biochemical parameters might assist clinicians to evaluate the prognosis of COVID-19.

Can we predict the severity of coronavirus disease 2019 with a routine blood test?

INTRODUCTION: The ongoing worldwide pandemic of coronavirus disease 2019 (COVID­19) has posed a huge threat to global public health. However, the issue as to whether routine blood tests could be used to monitor and predict the severity and prognosis of COVID­19 has not been comprehensively investigated so far. OBJECTIVES: This study aimed to provide an overview of the association of markers in the routine blood test with the severity of COVID­19. METHODS: PubMed, Embase, Cochrane Library, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies reporting data on markers in the routine blood test and the severity of COVID­19, published until March 20, 2020. The STATA software was used for meta­analysis. RESULTS: A total of 15 studies with 3090 patients with COVID­19 were included in this analysis. Patients in the nonsevere group, compared with those in the severe group, had lower counts of white blood cells (weighted mean difference [WMD], -0.85 [×109/l]; 95% CI, -1.54 to -0.16; P = 0.02) and neutrophils (WMD, -1.57 [×109/l]; 95% CI, -2.6 to -0.54; P = 0.003), greater counts of lymphocytes (WMD, 0.29 [×109/l]; 95% CI, 0.22-0.36; P <0.001) and platelets (WMD, 19.05 [×109/l]; 95% CI, 3.04-35.06; P = 0.02), and a lower neutrophil­to­lymphocyte (NLR) ratio (WMD, -2.48; 95% CI, -3.81 to -1.15; P <0.001). There was no difference in the monocyte count (WMD, 0.01 [×109/l]; 95% CI, -0.01 to 0.03; P = 0.029) between these 2 groups. Sensitivity analysis and meta­analysis based on standard mean difference did not change the conclusions regarding neutrophils, lymphocytes, and NLR, but yielded inconsistent results for white blood cells and platelets. CONCLUSIONS: Severe patients had more neutrophils, higher NLR level, and fewer lymphocytes than non-severe patients with COVID-19. Measurement of these markers might assist clinicians to monitor and predict the severity and prognosis of COVID-19.

Association of inflammatory markers with the severity of COVID-19: a meta-analysis

Objectives Studies reported associations of inflammatory markers with the severity of COVID-19, but conclusions were inconsistent. We aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods We searched PubMed, Embase, Cochrane Library, Wanfang and China National Knowledge Infrastructure (CNKI) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results A total of 16 studies comprising of 3962 patients with COVID-19 were included in our analysis. Random-effect results demonstrated that patients with COVID-19 in nonsevere group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = −8 mm/h, 95% CI = [-14, -2], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had a lower level for IL-6 than non-survivors (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might assist clinicians to monitor and evaluate the severity and prognosis of COVID-19.