BACKGROUND AND AIM:The exploration of age-related clinical characteristics and prognosis of severe fever with thrombocytopenia syndrome (SFTS) has not been extensively addressed in current research. This study aimed to analyze the differences in clinical features and outcomes of SFTS patients across various age groups. METHODS:Patients were assigned to four groups: those aged ≤ 54 years, those aged 55-64 years, those aged 65-74 years, and those aged ≥ 75 years. Then, their clinical data were compared. RESULTS:A total of 253 patients diagnosed with SFTS were retrospectively included. Compared with patients aged < 65 years, patients aged ≥ 65 years had higher serum levels of laboratory parameters indicating liver, kidney, heart, and coagulation system injury, as well as a higher viral load. Moreover, the serum levels of procalcitonin, SAA, ferritin, IL-6, IL-10, and TNF-α were significantly higher, but the percentages and counts of CD3+ and CD3 + CD4 + lymphocytes were significantly lower in patients aged ≥ 65 years than in patients aged < 65 years. The cumulative survival rate of patients aged ≥ 65 years was also significantly lower than that of patients aged < 65 years. Univariate and multivariate logistic regression analyses identified that age ≥ 65 years was an independent risk factor for the prognosis of patients with SFTS. CONCLUSION:Age significantly influences the clinical features and prognosis of patients, and age ≥ 65 years is associated with adverse outcomes in patients with SFTS.

BACKGROUND:Kaposi sarcoma (KS) is one of the most common tumors in patients with AIDS, while the occurrence of chylous effusions in KS patients is rare and often indicates a poor prognosis. This report present a case of successfully treated AIDS-associated KS complicated by both chylothorax and chylous ascites, along with a review of the relevant literature. CASE PRESENTATION:A 31-year-old male patient, who was recently diagnosed with HIV infection and oral KS at our clinic center, returned two weeks post-discharge. He reported significant enlargement of the oral tumor, increased abdominal girth with accompanying abdominal distension and pain, and a dry cough over the past week. Upon readmission, CT scans indicated the presence of extensive pleural and abdominal effusions. Aspirates from both the pleural and abdominal effusions exhibited a milky chylous appearance. After eliminating other potential etiologies for the chylous effusion, we associated it with the progression of KS. The patient's condition was ultimately successfully managed through a combination of antiretroviral therapy, systemic chemotherapy, and ntermittent thoracoabdominal paracentesis for drainage. CONCLUSIONS:The development of chylous effusions in patients with AIDS-associated Kaposi sarcoma signifies disease progression. Prompt initiation of systemic chemotherapy combined with antiretroviral therapy is critical for improving outcomes.

Talaromyces marneffei (TM) is a life-threatening opportunistic fungal pathogen, particularly in individuals with advanced HIV/AIDS. Early and accurate diagnosis remains challenging due to the limited sensitivity and specificity of conventional microbiological and antigen-based tests. Mp1p, a secreted TM-specific virulence protein, has emerged as a promising target for serological diagnosis. This study aimed to evaluate the diagnostic performance of Mp1p antigen and antibody detection using ELISA in sera from HIV infected patients with confirmed TM infection. A total of 36 confirmed TM-infected patients (including fungemia and non-fungemia cases), 269 HIV/AIDS patients with fever but without TM infection, 37 cryptococcosis patients, and 218 healthy blood donors were enrolled from two tertiary hospitals in China (2020–2024). Recombinant Mp1p protein was expressed and purified to develop Mp1p antigen and antibody ELISAs. Diagnostic sensitivity and specificity were calculated. Serial samples before and after antifungal therapy were evaluated to determine the utility of Mp1p antigen and antibody levels in treatment monitoring and recurrence detection. Results were compared with established diagnostic tools, including galactomannan (GM) and cryptococcal antigen (CrAg) assays. Mp1p antigen ELISA demonstrated high sensitivity (94.4

Pneumonia is common in patients with severe fever with thrombocytopenia syndrome (SFTS), and respiratory failure is one of its most severe complications. The aim of this study was to establish a nomogram for predicting respiratory failure development in SFTS patients with pneumonia. Data of demographics, comorbidities, clinical manifestations, laboratory parameters, complications, and outcomes of SFTS patients with pneumonia were collected. Independent predictors of respiratory failure development on multivariate logistic regression were used to construct the predictive model. Of the 167 SFTS patients with pneumonia we studied, 45 (26.9%) patients developed respiratory failure. Patients who developed respiratory failure had a higher incidence of invasive pulmonary aspergillosis, nosocomial infections, myocarditis, acute kidney injury (AKI) stage 2 or 3, rhabdomyolysis, shock, and systemic inflammatory response syndrome (SIRS). Among them, 35 patients died and all patients without respiratory failure survived. On multivariate regression analysis, neurological manifestations, nosocomial infections, AKI stage 2 or 3, SIRS, serum levels of albumin, and CKMB were proven to be independent predictors for respiratory failure development, which were adopted as parameters of the nomogram. The nomogram showed good calibration and discrimination, with an area under the receiver operating characteristic curve of 0.932 (95% CI 0.888-0.975). Decision curve analysis confirmed the clinical utility of the predictive model. Respiratory failure is associated with adverse outcomes including severe complications and death in SFTS patients with pneumonia. Clinicians could apply the nomogram to identify the high-risk pneumonic patients for developing respiratory failure.

Background Until recently, severe fever with thrombocytopenia syndrome (SFTS)-related disseminated intravascular coagulation (DIC) had not been elucidated. This study aimed to explore the clinical characteristics and outcomes of DIC in patients with SFTS. Methods Patients diagnosed with SFTS who were admitted to Zhongnan Hospital of Wuhan University from August 2016 to October 2023 were included. Patients’ demographics and clinical data were collected. According to the presence of DIC, they were assigned into the DIC and non-DIC groups. Independent risk factors for prognosis were identified by univariate and multivariate logistic regression analyses. Results A total of 246 consecutive patients diagnosed with SFTS were enrolled, including 216 (87.8%) patients in the non-DIC group and 30 (12.2%) patients in the DIC group. ALT, AST, ALP, GGT, LDH, creatinine, cystatin-C, amylase, lipase, CK, CK-MB, troponin I, BNP, PT, PTA, APTT, TT, FDP, D-dimer, CRP, procalcitonin, IL-6, SAA, ESR, ferritin levels, and viral load were significantly higher in patients with DIC. The cumulative survival rate of patients with DIC was significantly lower than that of patients without DIC. Furthermore, it is demonstrated that the presence of DIC was an independent risk factor for in-hospital mortality of patients with SFTS. Conclusion DIC is a potential complication and is associated with high mortality in patients with SFTS. Early recognition and timely management of this serious complication are important for patients with SFTS.

BACKGROUND:Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease triggered by a novel bunyavirus (SFTSV). The elderly population is vulnerable to infectious diseases. This study aimed to explore the clinical features and outcomes of elderly patients with SFTS and establish an effective prognostic nomogram for them. METHODS:Data on demographics, comorbidities, clinical manifestations, laboratory parameters, and outcomes of patients with SFTS were collected. Independent predictors for in-hospital mortality identified by multivariate logistic regression were used to construct the predictive model. RESULTS:253 patients with SFTS were retrospectively enrolled, including 142 (56.1%) elderly patients and 111 (43.9%) non-elderly patients. Compared with non-elderly patients, elderly patients had higher serum levels of laboratory parameters indicating liver, kidney, pancreas, heart, coagulation system injury, and higher viral load. The in-hospital mortality rate of elderly patients was significantly higher than that of non-elderly patients. The univariate and multivariate binary logistic regression analyses demonstrated that neurological manifestations, creatinine, CKMB, and prothrombin time were proven to be independent predictors for in-hospital mortality of elderly patients with SFTS, which were adopted as parameters of the nomogram. The nomogram showed a good calibration and discrimination, with an area under the receiver operating characteristic curve of 0.849 (95% CI 0.774-0.923). Decision curve analysis confirmed the clinical utility of the predictive model. CONCLUSIONS:Elderly patients are more susceptible to adverse outcomes, and the nomogram can help clinicians predict in-hospital mortality of elderly patients with SFTS, which may facilitate optimal therapeutic strategies to improve their prognosis.

Long noncoding RNAs (lncRNAs) are effective regulators of both RNA and protein functions throughout cell biology, including viral replication. Emerging studies have shown that lncRNAs activate or inhibit the replication and latency of HIV-1 by regulating different cellular mechanisms. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic lncRNA required for paraspeckle integrity and has been proven to be linked to viral infection. However, the mechanisms by which it influences HIV-1 infection in macrophages remain unclear. In this study, we performed RNA-deep sequencing to compare the profiles of lncRNAs in macrophages with or without HIV-1 and found that MALAT1 was dramatically upregulated in HIV-1-infected macrophages. MALAT1 knockdown inhibited HIV-1 infection, whereas MALAT1 overexpression enhanced viral replication, indicating that MALAT1 promotes HIV-1 replication. We further performed proteomics analysis and found that coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was the most downregulated protein affected by RNAi-mediated knockdown of MALAT1. We next demonstrated that MALAT1 favored HIV-1 replication in a CHCHD2-dependent manner and functioned as a competing endogenous RNA to regulate CHCHD2 expression by sponging miR-145-5p, which could mutually bind the MALAT1 and 3'UTR of chchd2 mRNA. Furthermore, knockdown of endogenous MALAT1 or CHCHD2 with specific small interfering RNAs (siRNAs) promoted the expression of IRF7, and enhanced the promoter activities of interferons-α and -β, increasing their production as well as that of a critical interferon-stimulated gene (ISG), myxovirus resistance protein B (MxB). Moreover, MALAT1 or CHCHD2 knockdown promoted the expression of STAT2 to enhance the production of downstream MxB, which expanded the role of CHCHD2 as a negative regulator of the innate immune response. These findings improve our understanding of MALAT1/miR-145-5p/CHCHD2 pathway regulation of HIV-1 replication in macrophages, providing new insights into potential targeted therapeutic interventions.

Combination antiretroviral therapy (ART) has improved outcomes for human immunodeficiency virus (HIV) associated non-Hodgkin lymphoma. This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era. The median CD4 count for the cohorts was 0.141 × 109/L (range, 0.001-0.861 × 109/L). DA-EPOCH ± R (54%) were most commonly used in HIV-BL. CHOP± R (42%) was most commonly used to treat HIV-DLBCL. The complete response rate after first-line curative therapy was 10/28 (36%) in HIV-BL and 25/57 (44%) in HIV-DLBCL. The 2-year progression-free survival (PFS) and overall survival (OS) for the HIV-BL cohort was 50% and 41% respectively. The 2-year PFS and OS for the HIV-DLBCL cohort was 55% and 47% respectively. Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China.

Objective This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM ( P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001–1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

IntroductionThis study aimed to assess the diagnostic values of bronchoalveolar lavage fluid (BALF) real-time polymerase chain reaction (PCR) and BALF metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PJP) in patients infected with human immunodeficiency virus (HIV).MethodsA total of 99 HIV-infected PJP patients and 61 HIV-infected patients diagnosed with non-PJP pneumonia between March 2019 and December 2022 were enrolled. P. jirovecii and multiple other co-pathogens detected in BALF by mNGS were analyzed. The clinical final diagnosis was employed as a benchmark. We compared the diagnostic performance of mNGS in PJP with serum BDG and BALF real-time PCR. The mixed infections detected by mNGS and modifications of antimicrobial treatment were also analyzed.ResultsThe sensitivity of mNGS test of BALF samples reached 85.86%, which was significantly higher than serum BDG (39.39%, P < 0.001). The sensitivity of BALF P. jirovecii PCR (84.85%) was similar with mNGS (P > 0.05). The specificity of mNGS (100%) was also same as PCR (100.0%), and superior to serum BDG (88.52%, P < 0.001). Besides, mNGS performs remarkably well in identifying co-pathogens of PJP patients infected with HIV. In addition to P. jirovecii, 82 cases (82.83%) of other co-pathogens were identified based on mNGS. Moreover, thirty-four patients (34.34%) increased therapeutic dose of trimethoprim-sulfamethoxazole (TMP-SMZ) based on BALF P. jirovecii PCR. Based on the mNGS results, initial antimicrobial treatment was modified in 86.87% (86/99) of PJP patients.ConclusionBALF mNGS and real-time PCR are two powerful techniques for rapid diagnosis of PJP with high specificity and sensitivity. Moreover, the benefit of mNGS is that it may identify other organisms besides PJP and it may benefit proper and prompt treatment.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis caused by a novel bunyavirus. Until recently, rhabdomyolysis in SFTS was not elucidated. The objective of this study was to investigate the prevalence and clinical characteristics of rhabdomyolysis and its association with AKI and prognosis in patients with SFTS. A total of 231 consecutive patients diagnosed with SFTS were enrolled, including 144 (62.3%) patients in the no rhabdomyolysis group and 87 (37.7%) patients in the rhabdomyolysis group. Clinical characteristics and laboratory parameters of SFTS patients were compared between the no rhabdomyolysis and rhabdomyolysis groups. Patients with rhabdomyolysis had more frequency of confusion, cough, sputum, chest distress, abdominal pain, petechia and ecchymosis, headache, myalgia, and myasthenia than those without rhabdomyolysis. Compared with patients in the no rhabdomyolysis group, patients in the rhabdomyolysis group had higher serum levels of laboratory parameters referring to liver, kidney, pancreas, heart, coagulation system injury, and higher viral load. The cumulative survival rate of patients with rhabdomyolysis was significantly lower than that of patients without rhabdomyolysis. Furthermore, univariate and multivariate binary logistic regression analyses demonstrated that rhabdomyolysis was an independent predictor for acute kidney injury and mortality in patients with SFTS. Rhabdomyolysis may be an important contributing factor to adverse outcomes and its effects on mortality may be mediated by acute kidney injury in SFTS. The early detection and effective intervention of rhabdomyolysis may decrease the mortality of patients with SFTS.

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X 2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods ( X 2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X 2 = 4.601, P = 0.032; 8/12 vs 5/23, X 2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.

OBJECTIVE:Respiratory viral diseases have posed a persistent threat to public health due to their high transmissibility. Influenza virus and SARS-Cov-2 are both respiratory viruses that have caused global pandemics. A zero-COVID-19 strategy is a public health policy imposed to stop community transmission of COVID-19 as soon as it is detected. In this study, we aim to examine the epidemiological characteristics of seasonal influenza in the past five years before and after the emergence of COVID-19 in China and observe the possible impact of the strategy on influenza. METHODS:Data from two data sources were retrospectively analyzed. A comparison on influenza incidence rate between Hubei and Zhejiang provinces was conducted based on data from the Chinese Center for Disease Control and Prevention (CDC). Then a descriptive and comparative analysis on seasonal influenza based on data from Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital before and after the outbreak of SARS-CoV-2 was conducted. RESULTS:From 2010-2017, both provinces experienced relatively low influenza activity until the 1st week of 2018, when they reached peak incidence rates of 78.16/100000PY, 34.05/100000PY respectively. Since then, influenza showed an obvious seasonality in Hubei and Zhejiang until the onset of COVID-19. During 2020 and 2021, there was a dramatic decline in influenza activity compared to 2018 and 2019. However, influenza activity seemed to rebound at the beginning of 2022 and surged in summer, with positive rates of 20.52% and 31.53% in Zhongnan Hospital of Wuhan University and Hangzhou Ninth People`s Hospital respectively as of the time writing this article. CONCLUSIONS:Our results reinforce the hypothesis that zero-COVID-19 strategy may impact the epidemiological pattern of influenza. Under the complex pandemic situation, implementation of NPIs could be a beneficial strategy containing not only COVID-19 but also influenza.

Long noncoding RNAs (lncRNAs) play important roles in regulating HIV-1 infection and virus-host interactions. However, it is unclear whether and how ART alters lncRNAs in HIV-infected patients. In the present study, we investigated changes of lncRNAs in PBMCs from HIV-1 patients pre- and post-ART. We identified a total of 974 lncRNAs whose expression was restored to normal levels after ART. Cis-acting analysis showed that six lncRNAs have cis-regulated target genes, among which RP11-290F5.1 and interferon regulatory factor 2 (IRF2) were reported to promote HIV replication. Furthermore, we found that lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression in PBMCs from HIV-1 infected patients after ART, was significantly upregulated by RNA-seq and qRT-PCR assays. KEGG analysis of CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway and pathways related to cell cycle and DNA replication. Our findings thus reveal the dynamic change of lncRNAs in people living with HIV-1 pre- and post-ART and warrant further investigation of the role of lncRNAs in HIV-1 pathogenesis and treatment.

Background:To analyze the changing characteristics of continuous monitoring of refined lymphocyte subsets in people living with HIV/AIDS (PLWHA) during ART period.Methods:Refined lymphocyte subsets was continuously monitored using flow cytometry for 173 PLWHA, who were hospitalized in Zhongnan Hospital of Wuhan University from August 17, 2021 to September 14, 2022. The effect of ART status and duration of ART on changes of refined lymphocyte subsets were compared in different groups. Then, the levels of refined lymphocyte subsets in PLWHA treated for more than 10 years were compared to those of 1086 healthy individuals.Results:In addition to conventional CD4+ T lymphocytes and CD4+/CD8+ ratio, gradually increasing in numbers of CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD45RA+CD3+CD4+CD25+CD127low and CD45RO+CD3+CD4+CD25+CD127low cells were found with the increase of ART duration. The number of CD4+CD28+ cells and CD8+CD28+ cells were 174/ul and 233/ul at 6 months post-ART, which gradually increased to 616/ul and 461/ul after ART initiation more than 10 years. Moreover, in ART ≤ 6 months, 6 months-3years, 3-10 years and >10 years groups, the percentage of CD3+CD8+HLA-DR+/CD8 were 79.66%, 69.73%, 60.19% and 57.90%, respectively, and the differences between groups showed statistical significance (F=5.727, P=0.001). For those PLWHA with ART more than 10 years, the levels of CD4+ T lymphocytes, CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD4+CD28+ cells and CD8+CD28+ cells can increase to levels similar to those of healthy control. However, for those PLWHA with ART more than 10 years, CD4+/CD8+ ratio was 0.86 ± 0.47, which was lower than that of healthy control (0.86 ± 0.47 vs 1.32 ± 0.59, t=3.611, P=0.003); absolute counts and percentage of CD3+CD8+HLA-DR+ cells were 547/ul and 57.90%, which were higher than those of healthy control(547/ul vs 135/ul, t=3.612, P=0.003; 57.90% vs 22.38%, t=6.959, P<0.001).Conclusion:Persistent ART can gradually improve the immune status of PLWHA, which is manifested in the increase of lymphocytes, function recovery of lymphocytes and reduction of aberrant activation status of the immune system. After 10 years of standardized ART, most lymphocytes could return to levels of healthy persons, although it may take longer to complete recovery for CD4+/CD8+ ratio and CD3+CD8+HLA-DR+ cells.

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

To establish a plasma model to predict the risk of liver fibrosis in HIV/HBV co-infected individuals. Quantitative liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to identify differentially expressed proteins (DEPs) in plasma collected from HIV/HBV co-infected individuals with and without liver fibrosis. In total, 97 DEPs were identified, among which 11 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. These markedly altered proteins were found to mediate pathophysiological pathways, including humoral immune response, complement and coagulation cascades, and complement activation. A visual logistic model, in which immunoglobulin heavy variable 3-20 (IGHV3-20), immunoglobulin heavy variable 1-24 (IGHV1-24), and macrophage colony-stimulating factor 1 receptor (CSF1R) proteins were included, has been established to predict liver fibrosis in HIV/HBV co-infected individuals. The preliminary conclusion showed that the combination of IGHV3-20, IGFHV1-24, and CSF1R is expected to become a predictive model for liver fibrosis in the context of HIV/HBV co-infection and a further validation should be performed.

Acquired immunodeficiency syndrome (AIDS) caused by Human immunodeficiency virus type 1 (HIV-1) has a high tendency among illicit drug abusers. Recently, it is reported that abuse of fentanyl, a potent synthetic mu receptor-stimulating opioid, is an independent risk factor for HIV-1 infection. However, the mechanism of action in augmenting HIV-1 infection still remains elusive. In this study, we found that fentanyl enhanced infection of HIV-1 in MT2 cells, primary macrophages and Jurkat C11 cells. Fentanyl up-regulated CXCR4 and CCR5 receptor expression, which facilitated the entry of virion into host cells. In addition, it down-regulated interferon-I3 (IFN-I3) and interferon-stimulated genes (APOBEC3F, APOBEC3G and MxB) expression in MT2 cells. Our findings identify an essential role of fentanyl in the positive regulation of HIV-1 infection via the upregulation of co -receptors (CXCR4/CCR5) and downregulation of IFN-I3 and ISGs, and it may have an important role in HIV-1 immunopathogenesis.

Abstract Background: COVID-19 still become a common threat to public health.In this study, we evaluated the antiviral effects and safety of darunavir/cobicisitat (DRV/c) in patients with confirmed COVID-19. Patients and Methods: Totally 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11, 2020 were collected. The patients were divided into the DRV/c group and the control group. The Primary endpoints was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens.Results: A total of 66 subjects with confirmed SARS-CoV-2 infection were enrolled in this study, 32 subjects were enrolled in the DRV/c group and 34 in the control group. The mean time to nucleic acid conversion (NAC) was shorter in DRV/c group. The cumulative nucleic acid conversion rate (CNACR) in the DRV/C group was higher during the first 2 weeks, but the difference was not statistically significant. The proportion of fever during hospitalization in the DRV/C group was significantly lower than that in the control group (P value 0.01). It was found that in DRV/c group NAC of patients with duration from symptom onset to admission within 3 days was significantly shorter (7.9 ± 6.7 days) than that of and above 3 days (15.9 ± 7.1 days)( P = 0.01). Conclusion: Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission, but no significant differences were observed between the DRV/c group and the conventional therapy group, including overall time to nucleic acid conversion, safety and tolerability.

Comorbidities are important for the disease outcome of COVID‐19, however, which underlying diseases that contribute the most to aggravate the conditions of COVID‐19 patients are still unclear. Viral clearance is the most important laboratory test for defining the recovery of COVID‐19 infections. To better understand which underlying diseases that are risk factors for delaying the viral clearance, we retrospectively analyzed 161 COVID‐19 clinical cases in the Zhongnan Hospital of Wuhan University, Wuhan, China between January 5 and March 13, 2020. The demographic, clinical and laboratory data, as well as patient treatment records were collected. Univariable and multivariable analysis were performed to explore the association between delayed viral clearance and other factors by using logistic regression. Survival analyses by Kaplan‐Meier and Cox regression modeling were employed to identify factors negatively influencing the viral clearance negatively. We found that hypertension and intravenous immunoglobulin adversely affected the time of viral RNA shedding. Hypertension was the most important risk factor to delay the SARS‐CoV‐2 virus clearance, however, the use of Angiotensin‐Converting Enzyme Inhibitors(ACEI)/Angiotensin Receptor Blockers(ARB) did not shorten the time for virus clearance in these hypertensive patients’ virus clearance. We conclude that patients having hypertension and intravenous immunoglobulin may delay the viral clearance in COVID‐19 patients.