Background: Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. Methods: Our study ( NCT04252885 , named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. Findings: This study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoints, the average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14, were similar between groups (all P >0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P >0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical( P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. Conclusions: LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. Funding: This study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004 and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).

Coronavirus Disease 2019 (COVID-19) is threatening billions of people. We described the clinical characteristics and explore virological and immunological factors associated with clinical outcomes. 297 COVID-19 patients hospitalized in Guangzhou Eighth People's Hospital between January 20 and February 20, 2020 were included. Epidemiological, clinical and laboratory data were collected and analyzed. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) RNA in respiratory tract, blood samples and digestive tract was detected and lymphocyte subsets were tested periodically. Among the 297 patients (median age of 48 years), 154 (51.9 %) were female, 245 (82.5 %) mild/moderate cases, and 52 (17.5 %) severe/critical cases. 270 patients were detected for SARS-CoV-2 RNA in anal swabs and/or blood samples, and the overall positive rate was 23.0 % (62/270), higher in severe/critical cases than in mild/moderate cases (52.0 % vs. 16.4 %, P < 0.001). The CD4/CD8 ratio on admission was significantly higher in severe/critical cases than in mild/moderate cases (1.84 vs. 1.50, P = 0.022). During a median follow-up period of 17 days, 36 (12.1 %) patients were admitted to intensive care unit (ICU), 16 (5.4 %) patients developed respiratory failure and underwent mechanical ventilation, four (1.3 %) patients needed extracorporeal membrane oxygenation (ECMO), only one (0.34 %) patients died of multiple organ failure. Detectable SARS-CoV-2 RNA in anal swabs and/or blood samples, as well as higher CD4/CD8 ratio were independent risk factors of respiratory failure and ICU admission. Most of COVID-19 patients in Guangzhou are mild/moderate, and presence of extrapulmonary virus and higher CD4/CD8 ratio are associated with higher risk of worse outcomes.

Background: HIV-associated talaromycosis causes substantial mortality despite available therapies. Early identification of high-risk patients remains challenging, particularly in resource-limited settings. We aimed to develop and validate a dynamic prognostic model for rapid risk stratification. Methods: This retrospective cohort study analyzed 1,892 HIV-talaromycosis patients admitted to Guangzhou Eighth People’s Hospital (2011–2023). Poor outcome (in-hospital death or deterioration-related discharge) was the primary endpoint. A nomogram was developed using Cox regression on admission variables in a training set (2011–2020, N = 1,435), with internal validation set (2011–2020, N = 431) and independent testing set (2021–2023, N = 457). Performance was assessed via time-dependent AUC, C-index, calibration, and decision curve analysis. Results: Poor outcomes occurred in 14.1% of cases (266/1,892), with 86.5% of these events happening within 28 days. Winter admissions exhibited the lowest case volume but the highest poor outcome rate. Multivariable analysis revealed eight independent readily available predictors: absence of lymphadenopathy (aHR: 0.581, 95%CI: 0.396-0.852, P = 0.005) and hepatosplenomegaly (aHR: 0.347, 95%CI: 0.232-0.519, P < 0.001), respiratory rate (aHR: 1.041, 95%CI: 1.007-1.076, P = 0.016), white blood cell count (aHR: 1.089, 95%CI: 1.049-1.132, P < 0.001), platelet count (aHR: 0.995, 95%CI: 0.992-0.997, P < 0.001), albumin level (aHR: 0.911, 95%CI: 0.872-0.952, P < 0.001), lactate dehydrogenase (aHR: 1.000, 95%CI: 1.000-1.000, P < 0.001), and blood urea nitrogen (aHR: 1.087, 95%CI: 1.068-1.106, P < 0.001). The above indicators were stratified according to predefined classifications and used to established a nomogram. The nomogram demonstrated strong discriminatory performance for 7-, 14-, and 28-day outcomes (AUC 0.905/0.863/0.838 in development; 0.851/0.832/0.807 in independent testing; C-index 0.813-0.841). Calibration curve analysis demonstrated that the nomogram exhibited excellent predictive accuracy and decision curve analysis indicated substantial clinical benefit. The model could effectively differentiate between high-risk and low-risk populations. Conclusion: This study provides a dynamically validated prognostic tool for HIV-associated talaromycosis, enabling risk stratification using readily available clinical data. Its integration into electronic health systems could off an opportunity to optimize resource allocation and improve outcomes in endemic regions.

This study investigated the molecular epidemiological characteristics of Cryptococcus neoformans (C. neoformans) isolates from AIDS patients with cryptococcal meningitis (CM) in southern China and examined their associations with clinical features and outcomes. A total of 100 clinical isolates were identified by MALDI-TOF MS and genotyped by multilocus sequence typing (MLST). Antifungal susceptibility to five agents was assessed using the FUNGUS 3 system. Baseline demographic, clinical manifestations, radiological, and laboratory data were collected from the corresponding 100 patients, and outcomes were evaluated at weeks 4, 12, 24, and 48. Seven sequence types (STs) were identified: ST5 (83/100, 83.0%), ST4 (5/100, 5.0%), ST31 (3/100, 3.0%), ST43 (1/100, 1.0%), ST93 (4/100, 4.0%), ST395 (1/100, 1.0%), and a presumptive novel ST685 (3/100, 3.0%). Most patients were male (80.0%), and headache was the most common symptom (85.0%). Susceptibility rates for 5-flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole were 98.9% (94/95), 71.9% (69/96), 82.3% (79/96), 59.4% (41/69), and 86.8% (59/68), respectively. Cumulative mortality reached 16%, 33%, 37%, and 39% at weeks 4, 12, 24, and 48. No significant differences were observed between 83 patients infected with ST5 and 17 patients with non-ST5 in clinical presentations or antifungal susceptibility. However, patients infected with ST5 exhibited consistently better survival rates across all time points, whereas those infected with ST93 showed the highest 12-week mortality. Accordingly, ST5 is the dominant sequence type of C. neoformans in HIV-associated CM in southern China; meanwhile, non-ST5 types could have worse prognosis, indicating ST sequence typing may act as a prognostic biomarker in AIDS patients with CM.